RxPG News : Endocrinology

Adenosine Kinase Deficiency (AKD) - a new inherited neurometabolic disorder

Sat, 01 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at the Swedish medical university Karolinska Institutet have discovered a new inherited disorder that causes severe mental retardation and liver dysfunction. The disease, adenosine kinase deficiency, is caused by mutations in the ADK gene, which codes for the enzyme adenosine kinase.

The findings, which are presented in the American Journal of Human Genetics, were made possible through the detailed biochemical examination of a Swedish family in which two children suffered from progressive brain damage and abnormal liver function that could not be traced to known mechanisms. One symptom displayed by the children was the impaired metabolism of the amino acid methionine. By sequencing all protein-coding gene sequences in the family – a process known as whole-exome sequencing – the team was able to identify a gene the function of which matched the biochemical abnormality. Whole-exome analyses were conducted at the Science for Life Laboratory (SciLifeLab) in Stockholm. Two additional unrelated families could then be identified with the same clinical profile and mutations in the same disease gene.

The findings illustrate the strength of combining the detailed biochemical examination of patients with the large-scale methods of analysing our genetic makeup that have recently become available, in order to expose new mechanisms behind congenital diseases. Modern tools of genetic analysis make it considerably easier to identify the damage responsible for hereditary diseases, which is essential if the affected families are to receive correct information about their disease. It is also a critical first step towards the development of new therapies.

The newly discovered disease, adenosine kinase deficiency, sheds light on an unexpected functional link between two known metabolic processes: the methionine cycle and adenosine/AMP metabolism, thus revealing a previously unknown pathogenetic mechanism. The study was led by Dr Anna Wedell, Professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet. Dr Wedell is also affiliated to Centre for Inherited Metabolic Diseases at the Karolinska University Hospital, the Center for Molecular Medicine, and the Science for Life Laboratory in Stockholm.

New UNC Center for Diabetes seeks to reduce health disparities

Mon, 26 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Chapel Hill, NC (September 26, 2011) -- The University of North Carolina at Chapel Hill has received a $3 million, 5-year grant from the National Institute of Diabetes and Digestive and Kidney Diseases to establish the UNC Center for Diabetes Translation Research to Reduce Health Disparities (CDTR). Its mission is to reduce diabetes-related disparities among poor and underserved populations by providing resources and support to foster translational research in North Carolina and beyond. The center's research will examine and compare different techniques for bringing effective preventive and therapeutic interventions into practice.

Currently, 1 in 9 adults in the U.S. (about 264 million) has Type 2 diabetes. If trends continue, projections suggest that 1 in 3 people may have the condition by 2050. Diabetes-related annual costs are currently $174 billion and may increase to $336 billion by 2034. Poor, minority and rural populations with limited access to health care suffer disproportionately. Especially in North Carolina, African-American, Hispanic and Native American populations have a higher rate of diabetes and related complications.

One of seven such centers in the nation established by the National Institutes of Health, the UNC CDTR will share resources and encourage collaboration on research that moves further along the translational continuum -- getting improved treatments applied in communities and validating that they make a difference. This critical step adds to the wealth of diabetes care and research already at UNC by over 200 researchers working on $350 million (since 2000) in funded research.

The UNC CDTR will leverage existing resources at the North Carolina Translational and Clinical Sciences (NC TraCS) Institute, home of UNC's NIH Clinical and Translational Science Awards (CTSA). NC TraCS is part of a national consortium whose mission is to accelerate movement of research discoveries into patient therapies and community interventions. The UNC CDTR also will partner with UNC-Pembroke, Robeson County Health Department, Wake Forest University and East Carolina University.

The co-directors are Richard Davis, M.D., and Michael Pignone, M.D., M.P.H.

Davis, an ophthalmologist with expertise in telemedicine and telehealth as tools to support community translational research, will lead efforts to utilize technologies to improve health outcomes. He also will direct the administrative core and the enrichment program in the center. Pignone, chief of the division of general medicine with expertise in development of novel means for improving chronic illness prevention and care, will lead a nationally designated resource center to study and improve literacy and numeracy in diabetes. Problems with literacy and numeracy are common, and less-literate and numerate patients have more difficulty managing diabetes, in particular, because of the high demands the condition places for tracking food intake, monitoring blood sugar levels and following complex medication regimens.

The CDTR has a goal of engaging researchers to move new knowledge into clinical practice and into communities to improve health for people living with diabetes, or to prevent diabetes in those individuals at risk for developing diabetes. Elizabeth Mayer-Davis, Ph.D., of the UNC departments of nutrition and medicine has worked in diabetes research for 20 years and will lead the CDTR pilot study program, which will fund new projects each year.

Alice Ammerman, Dr.P.H., a nutritionist who directs the UNC Center for Health Promotion and Disease Prevention, a CDC-funded prevention research center, will lead efforts to connect the UNC CDTR with communities where health disparities exist. Efforts will include involving community members in diabetes research and working closely with UNC-Pembroke and the Robeson County Health Department.

Ammerman already is a leader in forging academic-community connections through NC TraCS's Community Engagement Core. Davis is a research navigator at NC TraCS, who guides other researchers through the processes of applying for research funding and accessing resources to complete their projects. Pignone has been involved with the development of diabetes care guidelines for the American Diabetes Association, American Heart Association and the National Committee on Quality Assurance in Health Care.

The UNC CDTR is an example of how proposed new centers can leverage existing NC TraCS resources to enhance their proposals. Going forward the center will continue to rely on NC TraCS to help us more quickly translate research findings into better diabetes prevention strategies and treatments, said Davis. Our goal is improved health outcomes with regard to diabetes, not just in North Carolina but nationally.

Wayne State University study aims to improve diabetes management in high-risk youth

Fri, 23 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A little motivation for parents could go a long way toward improving young diabetes patients' ability to manage their own care, a Wayne State University researcher believes.

Deborah Ellis, Ph. D, associate professor of pediatrics in WSU's School of Medicine, has received a two-year, $418,000 grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health to develop and preliminarily validate a computer-delivered intervention to increase parental motivation to supervise and monitor diabetes management behavior of young adolescents who are beginning to manage their diabetes care by themselves. A companion intervention to increase the youths' own motivation to improve their diabetes care also will be developed as part of the study.

The study, Ellis said, is designed to address poor diabetes-related health outcomes among a particularly high-risk group: urban, African American youth with diabetes. Those disparities can be caused by higher insulin resistance and a greater number of single-parent households among African Americans compared to other groups, she said. Content currently is being developed; actual testing of the intervention is scheduled to start in two to three months.

Common sense might suggest that parents do need to oversee adolescents' diabetes management, Ellis said, but there's been a consistent finding in the literature that such supervision doesn't necessarily happen. Research shows that parents tend to back off as their children enter adolescence and let them have more responsibility for care than they are ready to manage.

We're trying to motivate parents to continue supervising and not simply rely on asking their child if diabetes care was done. The intervention will be delivered by computer, because if you're looking for something you can deliver widely, it's got to be brief and easily replicated, and if you're talking about medical care, it's got to take little time on the part of physicians and other health care providers, because they're very busy.

The study, to be conducted at diabetes clinics run by Dr. Kathleen Moltz, WSU assistant professor of pediatrics, will involve a computer program that uses the motivational interviewing approach. It is adapted from a program developed by grant co-investigator Steven Ondersma, Ph.D, WSU associate professor of psychiatry.

Recent research by Ellis' group has shown that parental supervision and monitoring of adolescents' daily diabetes care is a significant predictor of illness management and metabolic control. No results have been published for clinical trials of interventions that have directly targeted parental monitoring as a means of improving illness management in adolescents with diabetes.

Ellis' study will have three components. In the first, parents and adolescent will receive computer-delivered, motivation-building intervention. Parents will be encouraged to supervise diabetes care, and adolescents will be urged to complete all of their daily diabetes care.

Sex hormones impact career choices

Thu, 01 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Teacher, pilot, nurse or engineer? Sex hormones strongly influence people's interests, which affect the kinds of occupations they choose, according to psychologists.

Our results provide strong support for hormonal influences on interest in occupations characterized by working with things versus people, said Adriene M. Beltz, graduate student in psychology, working with Sheri A. Berenbaum, professor of psychology and pediatrics, Penn State.

Berenbaum and her team looked at people's interest in occupations that exhibit sex differences in the general population and are relevant to science, technology, engineering and mathematics (STEM) careers. The researchers studied teenagers and young adults with congenital adrenal hyperplasia -- a genetic condition -- and their siblings who do not have CAH.

People with CAH are exposed to more androgen -- a type of male sex hormone -- than is normal while in the uterus. Females with CAH are genetically female and are treated as females, but their interests tend to be more similar to stereotypically male ones.

The researchers report in the current issue of Hormones and Behavior that females with CAH were significantly more interested than females without CAH in careers related to things compared to careers related to people. The researchers also found that career interests directly corresponded to the amount of androgen exposure the females with CAH experienced -- those exposed to the most androgen in the uterus showed the most interest in things versus people.

We took advantage of a natural experiment, said Berenbaum. We're suggesting that these interests are pretty early developing.

Females without CAH had less interest than males in occupations related to things, such as engineer or surgeon, and more interest in careers focused on interacting with people, such as social worker or teacher. There was no significant difference reported between males with CAH and males without the condition.

We found there is a biological influence on that interest toward things, so maybe women aren't going into STEM careers because what they're interested in -- people -- isn't consistent with an interest in STEM careers, said Beltz. Maybe we could show females ways in which an interest in people is compatible with STEM careers.

The researchers asked the participants to rate each item in a list of 64 occupations, according to whether they would like, dislike or were indifferent to doing that job. The occupations were grouped into six categories of careers -- realistic, investigative, artistic, social, enterprising and conventional. This list and the categories are based on a well-established and validated system often used by vocational counselors.

The realistic and investigative categories reflect thing-oriented careers like farmer and scientist, social and artistic categories reflect people-oriented jobs such as teacher and artist, and the enterprising category was in the middle with occupations like realtor and hotel manager.

Simple blood test at high street opticians could help to diagnose diabetes

Tue, 30 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A simple finger prick test during routine eye examinations at high street opticians could help to identify millions of people with previously undiagnosed Type 2 diabetes, according to new research.

The researchers suggest earlier diagnosis could set people on the road to better management of the disease, which is the leading cause of blindness in the working age population, and that this could ultimately result in cost-savings for the NHS.

The Durham University study suggests that screening for the condition in unconventional settings, such as opticians, chiropodists or dentists, could find those people who would not routinely visit their GP, and could have potential worldwide.

It is estimated that 150 million people worldwide have diabetes but up to 50 per cent of people who have the condition are thought to be undetected and may only be diagnosed when complications occur.

It has already been shown that pharmacies and chiropodists have the capacity to carry out simple blood tests to identify Type 2 diabetes. The researchers say other places such as dentists could potentially be used to offer the test.

The pilot study, carried out by Durham University and The James Cook University Hospital in Middlesbrough, focused on opticians and the findings are published in the British Journal of General Practice.

It found that out of 1,000 people visiting their opticians for an eye test who were found to have one or more risk factors of diabetes, such as increased body mass index or aged over 40, almost 32 per cent were referred to their GP for further investigation after having their blood glucose levels checked.

The researchers say high street opticians are an under-utilised resource in the efforts to identify the large numbers of people with undiagnosed diabetes.

Currently, most screening for diabetes is carried out in medical settings, mostly by family doctors, but there are many people who do not visit their GP for preventative care, even if they are in an at-risk group.

While optometrists have an established role in screening people with known diabetes for eye disease, they are presently not involved in identifying diabetes.

Lead author and former optician, Dr Jenny Howse from Durham University's School of Medicine and Health, said: Charities' campaigns have managed to reduce the proportion of people with undiagnosed diabetes but there is still a 'hard-to-reach' group who remain undiagnosed. Opticians could provide routine, non-emergency care and the simple screening can be done outside usual medical settings, such as GP surgeries.

In the study, which involved five high street optometry practices, people were asked a number of questions to identify any diabetes risk factors. If they had one or more, optical assistants conducted a simple finger prick test, called a random capillary blood glucose (rCBG) test, to assess the blood glucose levels.

In keeping with current Royal Pharmaceutical Society and Diabetes UK guidelines for screening in pharmacies, those with raised blood glucose levels were advised to visit their GP for further investigations.

Dr Howse said: The screening test is less invasive and time consuming than fasting blood glucose and oral glucose tolerance tests.

Already pharmacists and chiropodists have shown it is feasible to offer screening in their practices, here in the UK as well as in Australia and Switzerland. In the US, 60 per cent of adults visit dentists at least once a year for standard check-ups and those practices could be suitable locations to screen for diabetes.

In the UK, our initial results show screening for diabetes in opticians is a feasible option but we now need to look at the practicalities of delivering it, including liaison between opticians and GPs and the time costs for opticians.

Type 2 diabetes is the most common type of diabetes and the risk of developing it increases as you get older. It develops when the body does not produce enough insulin to maintain a normal blood glucose level, or when the body is unable to effectively use the insulin that is being produced.

The study was set in five optometry practices of different sizes and locations in northern England with 1,002 people taking part in the research. 318 people had random capillary blood glucose (rCBG) levels of 6.1 or higher and so were advised to see their doctor for further tests and five had a rCBG of 12.1 or more who were told to see their GP urgently. 162 people took the advice and went to see their GP, and of these 138 reported they were investigated further. Nine people were diagnosed with pre-diabetes and seven with diabetes.

The research received funding from the Francis J Bell Fund, County Durham Community Foundation.

Strong association between the consumption of red meat and risk of type 2 diabetes

Wed, 10 Aug 2011 18:27:02 PST

( from http://www.rxpgnews.com ) A new study by Harvard School of Public Health (HSPH) researchers finds a strong association between the consumption of red meat—particularly when the meat is processed—and an increased risk of type 2 diabetes. The study also shows that replacing red meat with healthier proteins, such as low-fat dairy, nuts, or whole grains, can significantly lower the risk.

The study, led by An Pan, research fellow in the HSPH Department of Nutrition, will be published online in the American Journal of Clinical Nutrition on August 10, 2011 and will appear in the October print edition.

Pan, senior author Frank Hu, professor of nutrition and epidemiology at HSPH, and colleagues analyzed questionnaire responses from 37,083 men followed for 20 years in the Health Professionals Follow-Up Study; 79,570 women followed for 28 years in the Nurses' Health Study I; and 87,504 women followed for 14 years in the Nurses' Health Study II. They also conducted an updated meta-analysis, combining data from their new study with data from existing studies that included a total of 442,101 participants, 28,228 of whom developed type 2 diabetes during the study. After adjusting for age, body mass index (BMI), and other lifestyle and dietary risk factors, the researchers found that a daily 100-gram serving of unprocessed red meat (about the size of a deck of cards) was associated with a 19% increased risk of type 2 diabetes. They also found that one daily serving of half that quantity of processed meat—50 grams (for example, one hot dog or sausage or two slices of bacon)—was associated with a 51% increased risk.

"Clearly, the results from this study have huge public health implications given the rising type 2 diabetes epidemic and increasing consumption of red meats worldwide," said Hu. "The good news is that such troubling risk factors can be offset by swapping red meat for a healthier protein."

The researchers found that, for an individual who eats one daily serving of red meat, substituting one serving of nuts per day was associated with a 21% lower risk of type 2 diabetes; substituting low-fat dairy, a 17% lower risk; and substituting whole grains, a 23% lower risk.

Based on these results, the researchers advise that consumption of processed red meat—like hot dogs, bacon, sausage, and deli meats, which generally have high levels of sodium and nitrites—should be minimized and unprocessed red meat should be reduced. If possible, they add, red meat should be replaced with healthier choices, such as nuts, whole grains, low-fat dairy products, fish, or beans.

Worldwide, diabetes has reached epidemic levels, affecting nearly 350 million adults. In the U.S. alone, more than 11% of adults over age 20—25.6 million people—have the disease, according to the Centers for Disease Control and Prevention. Most have type 2 diabetes, which is primarily linked to obesity, physical inactivity, and an unhealthy diet.

Previous studies have indicated that eating processed red meats increases the risk of developing type 2 diabetes. Risks from unprocessed meats have been less clear. For instance, in 2010, HSPH researchers found no clear evidence of an association between eating unprocessed meats and increased risk for either coronary heart disease or type 2 diabetes, but that study was based on smaller samples than the current study, and the researchers recommended further study of unprocessed meats. Another HSPH study in 2010 linked eating red meat with an increased risk of heart disease—which is strongly linked to diabetes—but did not distinguish between processed and unprocessed red meats.

This new study—the largest of its kind in terms of sample size and follow-up years—finds that both unprocessed and processed meats pose a type 2 diabetes risk, thus helping to clarify the issue. In addition, this study is among the first to estimate the risk reduction associated with substituting healthier protein choices for red meat.

"Our study clearly shows that eating both unprocessed and processed red meat—particularly processed—is associated with an increased risk of type 2 diabetes," said Pan. He noted that the 2010 U.S. dietary guidelines continue to lump red meat together with fish, poultry, eggs, nuts, seeds, beans, and soy products in the "protein foods" group. But since red meat appears to have significant negative health effects—increased risk of diabetes, cardiovascular disease, and even total mortality, as suggested by several recent studies—Pan suggested the guidelines should distinguish red meat from healthier protein sources and promote the latter instead.

Type 2 diabetes: 'Intensive' versus 'conventional' blood glucose control -- no clear picture

Mon, 01 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Research published in The Cochrane Library found that the risk of death and cardiovascular disease, such as stroke, was unchanged whether glucose control was intense or conventional. They did find, however, that when aiming to keep blood glucose levels at the lower intensive level, the chance of damaging small blood vessels in the body, potentially leading to damage in the eyes and kidneys, is reduced. But aiming for this lower level with the more intensive glucose control substantially increased the risk that a person's blood glucose could drop too low, potentially resulting in loss of consciousness or even death if untreated.

Bianca Hemmingsen and colleagues from the Copenhagen Trial Unit in Denmark reached these conclusions after studying all published clinical trials comparing intensive glycaemic control with conventional glycaemic control. They identified 20 trials on patients with type 2 diabetes that together involved a total of 29,986 participants.

Keeping blood glucose levels under control is the goal of all treatments for people with type 2 diabetes. There is an active debate between experts about the level of blood glucose that patients should aim for. Some argue that they should aim to keep blood glucose about or slightly above normal, and thereby avoid the risks of too low blood glucose, what doctors call hypoglycaemia. Others think patients should use a more intensive control that keeps blood glucose at the lower levels seen in non-diabetic people so that they avoid the risks associated with having too much blood glucose - hyperglycaemia.

The researchers did not find enough information to properly compare quality of life between people who aimed for the two different targets. However, Hemmingsen and colleagues hypothesized that intensive glycaemic control may negatively affect a person's quality of life when compared with aiming for conventional levels. Targeting the intensive levels means that many patients have to cope with complex and time consuming treatment. On top of this, they have the fear that their blood glucose might drop too low, says Hemmingsen.

In most people, cells in their pancreas monitor blood glucose and release precise amounts of the glucose-regulating hormone insulin so that the glucose level is maintained. In people with type 2 diabetes, this insulin regulating system fails. These people have to manage their own glucose levels through a mixture of exercise, weight control, diet and the use of a range of different medications.

With the numbers of people in the world with type 2 diabetes increasing, it is important that we work out the best way of helping them to manage their blood glucose levels, says Hemmingsen. She believes that there is still a clear need for large clinical trials investigating patient-relevant outcomes that randomly assign patients to clearly defined different glycaemic targets.

$3 million grant to aid minorities with uncontrolled diabetes

Thu, 28 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Illinois at Chicago's Institute for Health Research and Policy and College of Medicine have received a $3 million federal grant to improve diabetes management in minority patients.

The grant will fund a five-year study to evaluate a new intervention designed to improve lifestyle behaviors and medication compliance and to intensify therapy in minority patients with uncontrolled type 2 diabetes.

African-Americans and Latinos with diabetes often do not reach desired blood sugar, blood pressure or cholesterol levels, placing them at high risk for complications or death.

We know there's a breakdown in the current health care system, said Lisa Sharp, assistant professor of medicine and co-principal investigator of the study. Even when patients have access to quality health care, there are many other economic, social and cultural factors that contribute to them not meeting their therapeutic goals.

The researchers will enroll 300 African-American and Latino adults with uncontrolled diabetes from the University of Illinois Medical Center. Patients will be randomly assigned to one of two groups.

In the first group, a clinic-based pharmacist will educate patients about diabetes, reconcile their medications, and address any compliance barriers.

In the second group, a community-based lay health worker (or health promoter) will team with the clinic-based pharmacist to assist with cultural and language barriers, reinforce educational messages, provide support, help solve problems related to compliance, and assist in continuity of care.

The pharmacist, working with a lay health worker, may help create a bridge, because there's this huge chasm between the patient and the health care provider, said Dr. Ben Gerber, associate professor of medicine. A lot of times, people will leave their doctor's office, and they have a lot of questions and don't understand things.

For example, a physician may prescribe a new insulin pen, but the patient may not know how to use it properly. The pharmacist may demonstrate it, but some patients may need additional practice that can be reinforced by a health promoter. Language barriers may also hinder understanding.

After one year, the participants who didn't receive health promoters will begin to receive health promoter support, while health promoter support for the other group will be phased out to assess maintenance and clinical outcomes.

There needs to be some adaptability to serve the patient's needs, said Gerber, co-principal investigator of the study.

Patients often bounce from the emergency room to the clinic to home and back again. Often there is a hands-off approach to figuring out what may be causing missed appointments or medication lapses, Gerber said.

Instead, we should try to figure out what the problems might be because if we address them it might actually help their ability to come to the clinic, to take their medicine, and maybe prevent them from being hospitalized, especially for diabetes-related problems, Gerber said.

Nordic study shows marginally higher but overall low risk of stillbirth in ART children

Wed, 06 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The group looked at 60,650 singletons in a common Nordic database from ART registers in Denmark, Finland, Norway and Sweden and compared these to a control group of 360,022 naturally conceived (NC) singletons. In both groups 0.4 % of singletons were stillborn, with a definition of stillbirth as a dead child after 22 weeks of gestation. After having been matched with the control group regarding mother's parity and year of birth, the overall risk of stillbirth was found to be marginally higher (1.1 fold) in ART children after adjusting for factors such as maternal age and the child's sex.

Although the difference in risk of stillbirth is significant between the two groups and the risk is marginally higher with an overrepresentation of 8 per 1,000 pregnancies for singleton ART pregnancies, the overall risk of stillbirth is still low, said Anna-Karina Aaris Henningsen, leading author of the study from Righospitalet University Hospital of Copenhagen. This means that the individual woman need not be concerned about the risk of stillbirth during pregnancy.

When analysing the stillbirth risk before and after term, no difference was found after 40 weeks of gestation between ART children and their naturally conceived peers. This was also the case when comparing the two cohorts after 37 weeks of gestation. However, until gestational week 40, the group found a 1.2 fold higher risk of stillbirth for ART singletons.

We believe the difference in risk of stillbirth between ART and NC children seems to occur before 37 weeks of gestation, said Dr. Aaris Henningsen. It is likely, that some of the difference in risk of stillbirth is related to parental factors in the subfertile mother or father.

When the researchers assessed the risk of total perinatal death (risk of stillbirth and risk of perinatal death until one year of age), children born after ART showed a 1.4 fold increased risk compared to naturally conceived babies. This remained 1.2 fold higher after adjusting for confounding factors and can probably be partly explained by the higher risk of preterm birth among ART children.

Very few European, non-Nordic, studies exist on stillbirth rates and are mostly based on small numbers, explained Dr. Aaris Henningsen. Our results come from the largest database on ART children worldwide. The MART group is currently looking at multiple neonatal outcomes including the risk of perinatal death in both singletons and twins and is hoping to have additional data in the near future.

Socioeconomic class and smoking linked to premature menopause

Wed, 06 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) POF is not only associated with infertility but also with significantly increased morbidity and mortality, as well as a decreased quality of life equivalent to that of people with type 2 diabetes or rheumatoid arthritis, said Dr. Rumana Islam, from Imperial College, London, UK.

Previous studies of POF, defined as the onset of menopause before the age of 40, have assessed the small group of women who seek hospital care, and therefore there is little information about the risks and impacts of POF across a whole population, Dr. Islam explained. With her colleague Dr. Rufus Cartwright, she studied the records of nearly 5000 women who formed part of the 1958 Birth Cohort. This included all the women born in Britain in a single week, explained Dr. Islam. They have been followed up eight times, most recently at age 50, when they were asked about the date and cause of their menopause and also their quality of life.

Out of the 4968 study participants, 370, or 7.4%, had either spontaneous or medically induced POF. In addition to the influence of social class, there was a strong independent association with smoking. Quality of life was measured using the SF-36 health survey, which produces a profile of physical and psychological health and well-being in eight areas. Women with POF were more than twice as likely to report poor quality of life, and this effect was not eliminated by taking confounding factors such as smoking, obesity, and physical exercise into account. There was also a profound impact on quality of life 10 years after POF, affecting vitality, physical function, mental health, and general health perceptions. However, social function was unaffected, said Dr. Islam.

POF is characterised by amenorrhea (the absence of periods), infertility, and sex steroid deficiency leading to menopausal symptoms in women aged under 40. Almost 20% of the women in the study who had undergone POF had done so as a result of early removal of the ovaries and/or hysterectomy, or as a consequence of chemotherapy. While hysterectomy has become less common over the last decade, our findings reinforce the recommendation that it should be a last resort for menstrual disorders, and that oophorectomy should be avoided in younger women, said Dr. Islam.

The researchers say that they have shown, for the first time, in a large cohort, the huge unrecognised physical and psychological burden of women among the general population with POF. This suggests an immediate need for primary care practitioners to screen for POF in women who present with amenorrhea before the age of 40, said Dr. Islam.

The average age at which women reach menopause is similar across different ethnic groups, and comparable findings are likely from other Western nations, the researchers say. Socioeconomic influences on health are pervasive, but often hard to disentangle, said Dr. Islam. Based on these data we can only speculate as to what they are, but the effect might be due to an unaccounted for environmental effect. Despite the availability of universal health care throughout these women's lives, there might also be differences in access to health care or differences in health behaviours.

However, our data provide a clear rationale for the management of POF symptoms by healthcare providers. We believe that women with POF can benefit from multidisciplinary specialist care, including support for their significant psychological and physical symptoms. Their long-term health needs should also be considered. Our study has shown POF has a major impact on the quality of life of a significant section of the population, and it needs addressing urgently, she concluded.

'Vanishing twin' explains increased risk of birth defects

Tue, 05 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Professor Michael Davies will tell the annual meeting of the European Society of Human Reproduction and Embryology today (Wednesday) that the vanishing twin phenomenon, in which only one child is born from a pregnancy that originally starts as a multiple pregnancy, is linked to a nearly two-fold increased risk in any congenital malformation and to a nearly three-fold risk of multiple malformations.

Prof Davies, who is an Associate Professor and co-director of the Research Centre for the Early Origins of Health and Disease at the University of Adelaide, Australia, will say: Our findings show that a 'vanishing twin' is a significant risk factor for congenital malformations in the surviving baby. This discovery means that we can now investigate what factors are occurring earlier in the process that could be influencing embryo development and loss. This has significant potential for advancing our understanding of the origins of congenital malformation, not just after infertility treatment, but also in spontaneously conceived pregnancies.

It is difficult to study what factors in early pregnancy might be causing congenital malformations such as heart and skeletal defects and cerebral palsy. This is because, in the general population, the majority of pregnancy losses, including vanishing twins, occur in the early days and weeks of pregnancy, often before the woman even knows that she is pregnant. The first ultrasound scans are usually carried out at around six to eight weeks. However, in women undergoing fertility treatment, early pregnancy is much easier to study because doctors know exactly when eggs were fertilised and transferred to the woman's womb, and this is followed by close monitoring with pregnancy tests and ultrasounds from the very beginning.

Prof Davies and his team studied data from all assisted reproductive technology (ART) cycles that took place in South Australia between January 1986 and December 2002, and linked them to registry data on birth defects and cerebral palsy. They identified cases in which a foetus had been lost by comparing routine six-week ultrasound data, which would show the presence of an empty foetal sac, and the number of babies actually delivered. These results were compared with pregnancies that had started off as single pregnancies and which had continued without loss of the foetus.

During this period 7,462 babies were delivered. In pregnancies where ultrasound had detected an empty foetal sac at six weeks, 14.6% of babies born had subsequent congenital malformations. The presence of an empty sac nearly doubled the risk of any malformation, and nearly trebled the risk of multiple malformations. Multiple pregnancies without any foetal loss were not associated with an increase in malformations when compared with single pregnancies without loss in the infertility group.

Prof Davies also looked at pregnancy loss after the first six weeks and he found that this was associated with birth defects in the surviving twin as well.

He will tell the conference: To our knowledge, this appears to be the first report of the association of very early loss of a co-twin and a range of congenital malformations. This result is important for several reasons. Firstly, it appears that the developmental competency, or 'quality' of embryos in twins is related. Where one fails to develop, it appears to be an important indicator of the health of the survivor. This is certainly a sensible interpretation within ART, where the embryos result from the same stimulation cycle and embryo culture conditions, and are returned together.

Test for chromosome abnormalities sheds light on genetic origins of faulty eggs

Tue, 05 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) At present, when a woman undergoes preimplantation genetic screening (PGS) in a fertility clinic, doctors are trying to select an egg or an embryo that is healthy and doesn't have a chromosome abnormality such as an extra copy of chromosome 21, which causes Down's syndrome. In order to establish this, they either have to biopsy a part of the egg called the polar body or remove a cell from the embryo for screening. Both procedures are expensive, invasive and can damage the egg or embryo.

Dr Elpida Fragouli, a research scientist at the University of Oxford and director of cytogenetics at Reprogenetics UK, will tell the annual meeting of the European Society of Human Reproduction and Embryology today (Wednesday) that she and her colleagues have discovered that cells surrounding the egg can provide information about the genetic and chromosomal status of the egg.

She explained: In the ovary, human eggs are surrounded by a cloud of tiny cells, known as cumulus cells. The egg and the cumulus cells are in constant communication and depend upon each other for continued viability. We wondered whether the presence of chromosome abnormalities, which are extremely common in human eggs and are incompatible with the formation of healthy embryos, would have an effect on the surrounding cumulus cells. This is important for two reasons. Firstly, an increase in the understanding of how chromosome abnormalities arise in eggs is desperately needed. For several decades we have been aware that chromosome problems are common in human eggs, that they are the major cause of miscarriage, and that they are responsible for conditions such as Down syndrome. Yet the origins of chromosome abnormalities remain poorly understood. A better understanding of the factors that lead to chromosome abnormality may help us think of ways to reduce their frequency.

Secondly, if chromosome abnormalities in the egg result in changes in the surrounding cumulus cells, it is possible that this could lead to a new way of testing eggs, before they are fertilised, revealing those with the correct number of chromosomes as well as those that are abnormal. This could help patients undergoing IVF, by identifying the eggs most likely to make a baby without having to use an invasive and expensive procedure. Cumulus cells are routinely stripped off eggs during IVF treatments and are usually discarded, so it should be straightforward to obtain them for analysis.

Dr Fragouli and her colleagues examined the polar bodies and cumulus cells from 26 eggs donated by women undergoing PGS. Polar bodies are by-products of egg formation. They contain the chromosomes discarded by the egg as it moves from having the same number of chromosomes as all the other cells of the body (46) to the number that eggs and sperm have (23). The unfertilised egg needs to discard half of its chromosomes in order to make way for those that will be delivered by the sperm. If things go wrong and a chromosome abnormality arises in the first polar body (e.g. an extra copy of chromosome 21), then the corresponding egg will have the reciprocal abnormality (e.g. a loss of chromosome 21). The researchers identified a total of 13 normal and 13 abnormal eggs by testing the polar bodies.

We then looked to see how active individual genes were in the cumulus cells that had surrounded each egg. This was done using two different methods. First we used a microarray, a powerful genetic technology that allows the activity of thousands of genes to be simultaneously tested. We found that 729 genes were expressed differently in cumulus cells that had surrounded eggs that contained an incorrect number of chromosomes. In other words, these genes were either more or less active than we would usually expect. In particular, 14 genes appeared to have highly significant differences in activity when their corresponding egg was abnormal, said Dr Fragouli.

We then used a second technique to confirm the initial findings. For this purpose we focused on 95 of the 729 genes that had been originally identified, including the 14 very significant genes. The method we used is known as real-time polymerase chain reaction (PCR). Real-time PCR is considered to be the most accurate way of quantifying the activity of genes, but is difficult to apply to large numbers of genes, which is why we used the microarray for the initial round of screening. The real-time PCR confirmed that most of the genes highlighted by the microarray do indeed show altered activity in cumulus cells associated with abnormal eggs.

We are still in the process of establishing the usefulness of these genes as non-invasive markers of egg chromosome status and quality. However, it is interesting that several of these genes are involved in vital cellular functions of the cumulus cells and egg they enclose, such as cell signalling and regulation, hormonal response and cell death, and so they may shed light on the genetic origins of chromosome abnormality.

The researchers are running further tests to see how well results from the expression of genes in cumulus cells compare with the more established PGS method for identifying faulty eggs. If there is a good correlation, then they plan to run a clinical trial in about a year's time.

The general idea is that instead of manipulating and biopsying the oocyte, a test examining the corresponding cumulus cells, which are currently discarded during regular IVF treatment, is developed. At the moment, as we are still working on this, I would envisage that results would potentially be obtained between three and five hours after egg retrieval. Theoretically, it would be possible to avoid fertilisation of abnormal eggs, which might have some ethical advantages over the current invasive methods that generally take longer. In addition, current diagnostic methods available for preimplantation genetic screening only provide information on the chromosome status of an egg. While this is a very important aspect of egg quality, it is not the only factor influencing the ability of the egg to lead to a successful pregnancy. The extra genetic information that we may be able to derive from examining the cumulus cells may give us a more detailed evaluation of an egg's potential to lead to a successful pregnancy and a healthy live birth, concluded Dr Fragouli.

Frozen embryo transfer leads to larger and heavier babies

Tue, 05 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) In the first study, French scientists looked at neonatal outcome in terms of mode of delivery, gestational age, preterm birth rate (less than 37 weeks of gestation), mean child measurements, low birth weight (less than 2,500g) and perinatal mortality. When comparing the cryo singletons to the fresh cohort, the scientists showed that mean birth weight, mean height and head circumference were lower in the fresh population. The mean birth weight of the cryo babies was 102g higher compared to the fresh cohort. Low birth weight for children born to term (more than 37 weeks) was also significantly lower in fresh babies. Low birth weight to normal birth weight ratio was twice as high in the fresh population (3.6% compared to 1.8%).

Frozen embryo transfer did not seem to adversely affect neonatal outcome, says Dr. Sylvie Epelboin, from Bichat-Claude Bernard Hospital, Paris. We are not sure why the cryo babies are heavier and larger, but we think it may have something to do with the hormonal hyperstimulation during the fresh cycles.

The researchers found no significant difference between the two cohorts in terms of preterm birth rate and mode of delivery. However, the boys to girls ratio was 1.05 times higher in the cryo group as was the IVF/ICSI ratio (84% compared to 65%). The ratio of women who had given birth once to multiparous women was 1.6 times higher in the fresh cohort. The group analysed 16,002 singletons, 2,140 of these children were in the cryo group and 13,682 were from fresh embryo transfers.

In a second study from Denmark Dr. Anja Pinborg and her group from the Rigshospital at Copenhagen University compared intrauterine parameters of 910 singletons born after frozen embryo transfer (FET) with 9,603 babies from fresh embryo transfer and 4,656 naturally conceived (NC) children. The rate of large-for-gestational age (LGA) babies was significantly different between the three groups with 16.9% for FET, 10.3% for fresh transfer and 11.4% for NC babies. The same applied to the rate of babies with birth weight of 4,500g or more (5.6%, 2.8% and 3.4% respectively).

Cryopreservation of embryos can result in 'Large Offspring Syndrome', which may be explained by epigenetic changes in the very early embryonic stages caused by freezing and thawing procedures, says Dr. Pinborg. Future studies must look into the precise epigenetic changes causing LGA offspring in humans. In animal studies, there is evidence that abnormal gene expression of certain developmentally important genes may be responsible for the observed large offspring syndrome.

The risk for a baby to be too heavy for the gestational age at birth is increased 1.6 fold compared to children from fresh embryo transfer and 1.5 fold compared to naturally conceived children. The group found a similar significant pattern for small-for-gestational age (SGA) children. Only 9.2% of FET singletons were SGA compared to 14.8% in fresh IVF and ICSI and 11.3% in NC children.

We think that because in FET cycles hormone supplementation mimics the natural cycle, compared to the superphysiologically high hormonal stimulation of women in fresh cycles, this 'similar-to-natural-cycle concept' may influence endometrial receptivity, early implantation and placental development in a positive way, leading to higher foetal growth and higher mean weight, Dr. Pinborg will say.

Placenta previa (PP)* was seen in 0.9% of FET pregnancies compared to 1.5% of fresh IVF/ICSI and 0.3% of NC children. However, these figures were not significantly different and there was no association between PP and the risk of being SGA in any of the cohorts. This lower risk in placenta previa in FET compared to the other groups may be explained with alterations in the endometrial contractility, says Dr. Pinborg. Ovarian stimulation and/or oocyte retrieval may induce alterations in the endometrial contractility leading to fewer implantation sites than in the unstimulated frozen cycles. The transcervical embryo replacement may also have some impact and hence lead to a higher placenta previa rate in FET compared to natural cycles.

Babies with a high birth weight may face an increased rate of delivery by Caesarean section and obstetric intervention causing complications for both mother and baby.

Long term prognosis for life birth after RM

Mon, 04 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The researchers studied the records of 987 women with a minimum of three consecutive miscarriages, who had been referred to a specialist RM clinic between 1986 and 2008. Using data from the National Danish Birth Register they were able to see how many of the women had achieved a live birth after referral to the clinic. They also looked at the impact of maternal age at the time of referral, and the number of previous miscarriages as prognostic markers for future live births. The ages of the women at referral to the clinic ranged from 20 to 46 years.

We found that, of all the women included in the study, 66.7% had achieved a subsequent live birth within five years after their first consultation in our clinic, and that this increased to 71.1% within 15 years after the first consultation, study leader, Professor Ole Christiansen, told a press conference. The next step will be to compare the fecundity (ability to get pregnant resulting in live birth) of women with RM to that of an age-matched group of women from the general population with an equally strong wish to conceive since we are not, from the present study, able to conclude with regards to that.

The women attending the clinic are encouraged to try to become pregnant, are closely monitored and receive appropriate treatment if relevant risk factors are present. However, in this study we did not specifically look at the effect of different treatments, said Ms Lund.

There are a number of possible reasons why some women attending the clinic did not have a live birth after referral, according to the researchers. One reason could be that they continue to miscarry in all subsequent pregnancies, but others could simply be due to increased age at each attempt, or damage to the Fallopian tubes caused by post-miscarriage pelvic inflammation. Additionally, the couple may eventually give up trying for a pregnancy due to fear of another miscarriage, or the pregnancy attempts are given up due to divorce.

Most studies of RM to date have looked at miscarriage rate in the next pregnancy as an outcome measure. Because an essential part of the management of couples with RM is to be able to advice on the prognosis for future pregnancy outcome, we performed this study to investigate the outcome measure of live birth after a certain time period, since we believe this is more relevant from the patient's perspective and also more transparent than just looking at miscarriage rate in the next pregnancy. We hope that estimating the chances having a live-born child will give couples affected by RM a more realistic prognosis for future pregnancy success, Professor Christiansen concluded.

Women with recurrent miscarriage have a good chance of having a pregnancy and live birth

Mon, 04 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Dr. Stef Kaandorp, from the Centre for Reproductive Medicine, Academic Medical Centre, Amsterdam, The Netherlands, said that his group's research was the first to look at time to natural conception in women with RM, and that its results would help health professionals to advise and treat patients appropriately.

In a subset of the ALIFE study, which investigated the effect of aspirin alone or combined with low-molecular-weight heparin, compared to placebo, on the live birth rate in women with unexplained RM, the researchers looked at the length of time between the moment of randomisation to the moment of the first day of last menstruation before the subsequent pregnancy. 251 women were included in the subset, and the mean age at the time of diagnosing unexplained RM was 34 years. The women had all had at least two miscarriages with an upper gestational age of 20 weeks.

213 women became pregnant during the period February 2004 to July 2009. 139 had a live birth, 69 a miscarriage, two an ectopic pregnancy, two a termination of pregnancy and one had an intra-uterine foetal death. The median time to a subsequent pregnancy, irrespective of outcome, was 21 weeks. The cumulative incidence of natural conception was 56% after six months, 74% after 12 months, and 86% after 24 months of which 65% resulted in a live birth.

These women were all randomised to receive one of the treatments or placebo, but further analysis showed that these made no difference to the outcome. Even such factors as maternal age, BMI, the number of previous miscarriages and the presence or absence of a previous live birth did not alter results significantly. Only the presence of Factor V Leiden significantly predicted a shorter time to conception, said Dr. Kaandorp. Factor V Leiden is a specific gene mutation that results in thrombophilia (an increased tendency to form abnormal clots that can block blood vessels).

Factor V Leiden mutation was present in 11 women; 64% of the pregnancies in these women resulted in a live birth as opposed to 65% in the women who did not carry the mutation, said Dr. Kaandorp. This mutation is usually associated with recurrent miscarriage, so finding a shorter time to pregnancy in the group carrying the mutation is very interesting and we intend to investigate it further.

The researchers now intend to follow up their work by looking at the time it took to achieve a live birth as opposed to simply time to pregnancy. This will be important in counselling these women for their future pregnancy attempts, said Dr. Kaandorp. We hope that our work will encourage health professionals to avoid non evidenced-based and potentially harmful treatments for couples. For example, aspirin and low-molecular-weight heparin are still being used, even though the ALIFE study showed clearly that there is no evidence that they are helpful.

Our results mean that women with RM can be reassured that their time to a subsequent conception is not significantly longer than that for fertile women without a history of miscarriage. RM is extremely stressful for these women and we hope that our study will give them hope and encourage them to keep trying for the baby they want so much, he concluded.

Could ovarian stimulation cause an increase in chromosome copy number abnormalities?

Sun, 03 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers involved in ESHRE's polar body screening study (launched in 2009) will tell the annual conference of the European Society of Human Reproduction and Embryology today (Monday) that results from the study are leading to a new understanding about how such abnormalities are developing, and they believe that the ovarian stimulation a woman receives might be playing a part. Understanding the mechanisms involved could help older women who are trying to have a healthy baby with their own oocytes.

Professor Alan Handyside, Director of The London Bridge Fertility, Gynaecology and Genetics Centre, London, UK, and colleagues from eight countries undertook a proof of principle study of a novel method of screening polar bodies, small cells that are the by-product of oocyte development, using the new technology of microarray comparative genomic hybridisation (array CGH) in order to find whether this was a reliable method of analysing the chromosomal status of an oocyte. This is because many more chromosome copy number abnormalities arise in the oocyte than in sperm.

In doing so, we obtained a lot of data at the individual chromosome and chromatid level, says Professor Joep Geraedts, co-ordinator of the ESHRE Task Force on preimplantation genetic screening (PGS). (A chromatid is one of the two identical copies of DNA making up a duplicated chromosome). So we decided to analyse these data separately to see whether they could provide us with information that could be useful in determining better treatment strategies for the future.

In this unique study, we were able to use the new technology of array CGH to examine the copy number of all 23 pairs of chromosomes, in all three products of female meiosis in over 100 oocytes with abnormal numbers of chromosomes, says Professor Handyside. What happens in female meiosis is that the 23 pairs of chromosomes duplicate and each pair of duplicated chromosomes comes together and the four single chromosomes, or 'chromatids', become 'glued' together along the whole length of each chromosome. This actually occurs before the woman is born and is the stage at which DNA is swapped between the grandparents' chromosomes.

Sometimes, decades later, just before ovulation, the glue 'dissolves' first between the two duplicated chromosomes and finally after fertilisation between the two individual chromosomes. This enables pairs of chromosomes to segregate in the first meiotic division producing the first polar body. In the second meiotic division the second polar body is produced, resulting in a single set of chromosomes in the fertilised oocyte or 'zygote', which, when combined with the single set in the fertilising sperm, restores the 23 pairs, he says.

The researchers believe that ovarian stimulation may be disturbing this process in older women because the chromosomes are becoming unglued prematurely, particularly the smaller ones like chromosome 21. Ovarian stimulation uses hormonal medication to stimulate the ovaries to release a large number of oocytes than normal, in order to provide enough good quality oocytes for fertilisation in vitro.

Following natural conception in older mothers, Down's pregnancies are predominantly caused by errors in the first female meiotic division. Our evidence demonstrates that, following IVF, there are multiple chromosome errors in both meiotic divisions, suggesting more extensive premature separation of single chromosomes resulting in more random segregation, which in turn results in multiple chromosome copy number changes in individual oocytes, says Professor Handyside.

We need to look further into the incidence and pattern of meiotic errors following different stimulation regimes including mild stimulation and natural cycle IVF, where one oocyte per cycle is removed, fertilised and transferred back to the woman. The results of such research should enable us to identify better clinical strategies to reduce the incidence of chromosome errors in older women undergoing IVF.

We also believe that our research will help identify women who want to have their own offspring but have practically no chance of doing so that we can advise them to use donor oocytes, says Professor Geraedts. This in itself is already a big step forward that will aid couples hoping for a healthy pregnancy and birth to be able to achieve one.

Teens with type 2 diabetes already show possible signs of impaired heart function

Tue, 07 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Heart function may be affected in people with Type 2 diabetes as early as adolescence, according to a new study that will be presented Sunday at The Endocrine Society's 93rd Annual Meeting in Boston.

Past studies in adults with Type 2 diabetes show that their heart and blood vessels' ability to adapt to exercise may be impaired. Our study shows that these changes in heart function may begin to happen very early after Type 2 diabetes occurs, said the study's lead author, Teresa Pinto, MD, a pediatric endocrinologist at the Dalhousie University IWK Health Centre in Halifax, Nova Scotia, Canada.

Pinto performed the research while at the University of Auckland in New Zealand. The researchers studied how the heart and blood vessels of 13 teenagers with Type 2 diabetes adapted to exercise, compared with 27 overweight or obese subjects who did not have diabetes and 19 nondiabetic and nonobese control subjects. The subjects were ages 12 to 20 and from New Zealand. Their body composition, including percentage of body fat, was determined using dual-energy x-ray absorptiometry (DEXA) scans.

All subjects performed an exercise test on a stationary bicycle designed for use in a magnetic resonance imaging (MRI) machine. With MRI, images were taken of each subject's heart and femoral artery, a large blood vessel in the leg that supplies the leg with blood. MRI took place while the subjects were at rest and during or immediately after exercise on the cycle.

The images of the heart showed that the hearts of subjects with Type 2 diabetes did not expand and fill up with blood between heart beats as well as the hearts of subjects in the other two groups. This occurred during exercise only, the authors found. With exercise, the amount of blood pumped out with each heart beat (the cardiac output) was normal in all three groups, although still lower in the diabetic group.

We showed that the heart's pumping function is strong, but it is not filling as well as normal between heart beats. This is known as diastolic dysfunction, Pinto said. Although this study did not determine the reason for this, we know that with diabetes, the heart can become stiffer, limiting its ability to stretch and expand.

In addition, images of the femoral artery showed that the flow of blood through the artery was significantly less in the diabetic group during exercise compared with the other two groups.

It appears that irrespective of weight, Type 2 diabetes seems to have a negative effect on the heart and blood vessels in adolescents, Pinto said. This impaired exercise capacity may be reversible with exercise training however, as some literature in adults suggests, but further studies are required to determine this.

Excessive pregnancy weight gain raises the risk of having a fat baby

Tue, 07 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Women who gain too much weight during pregnancy tend to have newborns with a high amount of body fat, regardless of the mother's weight before pregnancy, a new study finds. The results will be presented Tuesday at The Endocrine Society's 93rd Annual Meeting in Boston.

High fat at birth is a possible risk factor for childhood obesity, said the study's principal investigator, Jami Josefson, MD, a pediatric endocrinologist at Chicago's Children's Memorial Hospital and assistant professor at Northwestern University Feinberg School of Medicine.

Previous studies have shown that children of mothers who gain too much weight during pregnancy are more likely to be overweight for their age, Josefson said. However, not all these studies accounted for the mother's diabetes status during pregnancy, which is a known risk factor for offspring obesity.

The new study evaluated only pregnant women without gestational diabetes, therefore ruling out the chance that this disorder could account for their findings.

Josefson and her colleagues wanted to learn whether pregnant women who gain more than the recommended amount of weight have fat infants. Doctors, however, do not typically measure a newborn's body fat, she said. Many past studies that measured newborn body fat used an imprecise method, such as skin fold thickness, according to the authors' abstract.

This study used a new infant body composition system (Pea Pod) that employs an air-displacement technique, which Josefson said accurately and safely measures newborn body fat. This technique requires the infant to simply lie in a machine for two minutes, she said. Newborns in the study underwent measurements of length, weight and fat within 48 hours of birth.

Of the 56 mothers the researchers studied, 31 women were within guidelines for pregnancy weight gain, and 25 exceeded the guidelines. The Institute of Medicine recommends that women at a healthy weight before pregnancy gain 25 to 35 pounds while expecting a single baby; overweight women, 15 to 25 pounds; and obese women, 11 to 20 pounds.

Study subjects who were obese before pregnancy were more likely than healthy-weight women to exceed the weight-gain guidelines (70 percent versus 31 percent, respectively), the authors reported. Yet regardless of pre-pregnancy weight, women who put on more than the recommended weight gave birth to significantly fatter babies. Their newborns had 490 grams, or 17.5 ounces, of body fat, whereas newborns of women who stayed within the guidelines had 390 grams (13.9 ounces) of fat. This higher obesity risk existed even when birth weight was normal.

Excessive weight gain during pregnancy, regardless of pre-pregnancy weight, is an important risk factor for newborn obesity, Josefson said. More research is needed to determine if high amounts of fat at birth are associated with high amounts of fat in childhood.

Low vitamin D levels are related to decreased response to osteoporosis medicine

Mon, 06 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Women with low bone density are seven times more likely to benefit from a bisphosphonate drug when their vitamin D blood levels are above recent recommendations from the Institute of Medicine (IOM) as adequate for bone health. These new study results will be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

Maintaining adequate vitamin D levels above those recently recommended by the IOM is important for optimizing a standard therapy for osteoporosis: bisphosphonates, said coauthor Richard Bockman, MD, PhD, chief of the endocrine service at Hospital for Special Surgery and professor of medicine at Weill Cornell Medical College, both in New York City.

Last November the Institute of Medicine (IOM) issued its recommendations on vitamin D intake, reporting that most adults up to age 70 need no more than 600 International Units, or IU, a day to maintain bone health. According to the IOM, this intake, along with adequate calcium, is enough to achieve the minimum adequate vitamin D blood level, measured as serum 25-hydroxyvitamin D, which is 20 nanograms per milliliter (ng/mL).

However, in Bockman's study of 160 postmenopausal women with osteoporosis, an average 25-hydroxyvitamin D level of 20 to 30 ng/mL was associated with a high likelihood of not responding to at least 18 months of bisphosphonate treatment. Patients took alendronate, risedronate, ibandronate or zolendronate. The rate of women who were nonresponders at this serum vitamin D level was 77.8 percent, compared with 42.3 percent when serum vitamin D was in the range of 30 to 40 ng/mL. Only 24.6 percent were nonresponders for a level above 40 ng/mL, the authors reported.

Patients with a hydroxyvitamin D level of 33 ng/mL and above had a sevenfold greater likelihood of having a favorable response to bisphosphonate therapy than below that level, they found.

This value of at least 33 ng/mL is higher than the level considered as adequate by the Institute of Medicine report for the general population and most likely requires a vitamin D intake higher than 600 IU for this therapeutic outcome, Bockman said. In the future, I think we're going to see vitamin D recommendations based on specific conditions.

The researchers categorized patients as nonresponders if they had a new fracture while receiving a bisphosphonate or if their low bone density worsened by more than 3 percent as shown on dual-energy x-ray absorptiometry (DEXA) bone density scans obtained 18 to 60 months apart. Also counted as a nonresponder was any woman with a persistently low DEXA T-score worse than -3 (3 standard deviations below normal).

A typical nonresponse rate to bisphosphonate treatment, according to Bockman, is about 30 percent in an osteoporosis specialty clinic, such as the one from which participants in this study were recruited. Doctors do not generally measure a patient's serum vitamin D level before beginning bisphosphonate treatment, he said.

Desserts with a low glycemic index may benefit weight-loss efforts for obese children

Mon, 06 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Overweight girls lose more weight and can better stay on a healthy diet if they eat sugar-free, low-fat desserts several times weekly, as opposed to any dessert once a week, a new study finds. The results will be reported Monday at The Endocrine Society's 93rd Annual Meeting in Boston.

Dieters commonly splurge on dessert once a week, usually choosing fattening items, said lead investigator Antonia Dastamani, MD, PhD, a pediatrician and research fellow at Athens University School of Medicine in Athens, Greece. However, we found a positive effect of more frequent consumption of desserts that have a low glycemic index and low glycemic load.

Carbohydrates have a low glycemic index (GI) if they raise glucose, or blood sugar, levels more slowly than other carbohydrates do. The glycemic load (GL), which depends on serving size, is the food's total effect on blood sugar.

Studies suggest that low GI/GL diets have a positive effect on weight control and improving insulin resistance, Dastamani said.

Obesity can cause insulin resistance, in which the body does not properly use the hormone insulin. This results in high blood sugar levels and sets the stage for development of diabetes.

Dastamani and her colleagues tested the effects of incorporating into a balanced diet certain low-calorie, low-GI/GL desserts containing sugar substitutes such as sucralose. The products are made by the Giotis Company, a food production company in Athens, which donated the desserts and helped fund the study.

The investigators studied the effects of two diets in 29 girls, ages 10 to 14 years, who had a body mass index (BMI) in the 85th percentile or above, considered overweight or obese. A group of 15 girls ate a diet consisting of 45 percent carbohydrates, 35 percent fats and 20 percent proteins, including the low-GI/GL desserts four times a week. The other group of 14 girls followed the same diet except, instead of the low-GI/GL desserts, they ate desserts of their choice once a week.

After three months on the diet, both groups improved their BMI (body composition). Compared with the second group, however, the group that ate the low-GI/GL desserts lost significantly more weight and had better average BMI and systolic blood pressure (the first number in a blood pressure reading), the authors reported.

Girls who ate the low-GI/GL desserts also had significantly improved levels of the appetite-suppressing hormone leptin, the researchers found. They also had better improvements in biochemical markers of insulin resistance (fasting insulin levels in the blood and the homeostatic model assessment, or HOMA, index).

Childhood obesity is pandemic, and dietary changes among overweight and obese children must be a priority, Dastamani said. Desserts with a low glycemic index and glycemic load, when eaten in moderation, are valuable tools in the treatment of pediatric obesity.

Intravenous nutrition in critically ill patients should be delayed, study finds

Mon, 06 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Patients in the intensive care unit who do not tolerate adequate nutrition from tube feeding should wait a week before receiving intravenous (IV) feeding because, compared with early IV feeding, it enhances recovery from critical illness. Results of a new multicenter study from Belgium will be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

These findings have enormous impact for improving quality and reducing the cost of medical care for critically ill patients, said the study's principal investigator, Greet Van den Berghe, MD, PhD, a professor at the Catholic University of Leuven.

Results of this large randomized, controlled clinical trial contradict European clinical guidelines on IV nutritional support in ICU patients, and lend support to American and Canadian recommendations. Van den Berghe said, The standard of care in Europe should change.

At issue is the optimal timing to initiate parenteral nutrition (PN), also called IV feeding, in critically ill patients who are not getting enough calories through the gut by enteral nutrition, or tube feeding. To avoid ICU patients becoming weak from nutritional deficit, European experts recommend that they begin PN within two days of admission to the ICU, Van den Berghe explained. However, PN is linked to an increased frequency and severity of hyperglycemia, or high blood sugar. Experts in the U.S. and Canada advise withholding PN during the first week in the ICU if patients were not malnourished before admission.

Until now there has been no good scientific evidence to support either of the widely implemented nutritional strategies in intensive care, she said.

This study, called the EPaNIC trial for Early Parenteral Nutrition to supplement insufficient enteral nutrition in Intensive Care patients, compared the timing of PN initiation in adults at seven ICUs in Belgium who were at risk of malnutrition. Of the 4,640 participants, 2,312 patients were randomly assigned to receive early PN (within 48 hours of admission), and 2,328 received late PN (no earlier than day 8 in the ICU). Both groups received early enteral nutrition support and insulin to target normal blood sugar levels.

The researchers found that late PN was superior to early PN, with time in the ICU a median of one day shorter. Withholding IV nutrition for one week in the ICU, even in patients who could not be fed at all via the normal enteral route, surprisingly accelerated alive discharge from the ICU and from the hospital, without threatening their ability to function, Van den Berghe said.

Late PN also lowered the frequency of complications compared with early PN, including reducing severe infections (22.8 versus 26.2 percent, respectively), the authors reported. Also, late PN shortened the time on a ventilator and on dialysis, thus allowing faster recovery from organ failure, and it prevented liver function abnormalities, Van den Berghe said.

The investigator-initiated study received funding from the Fund for Scientific Research in Flanders, Belgium, the Catholic University of Leuven (GOA), and the Methusalem program from the Flemish government in Belgium. A nonrestricted grant to the Catholic University of Leuven came from Baxter Healthcare in France.

Cut down on 'carbs' to reduce body fat, study authors say

Sun, 05 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A modest reduction in consumption of carbohydrate foods may promote loss of deep belly fat, even with little or no change in weight, a new study finds. Presentation of the study results will be Sunday at The Endocrine Society's 93rd Annual Meeting in Boston.

When paired with weight loss, consumption of a moderately reduced carbohydrate diet can help achieve a reduction of total body fat, according to principal author Barbara Gower, PhD, a professor of nutrition sciences at the University of Alabama at Birmingham.

These changes could help reduce the risk of developing Type 2 diabetes, stroke and coronary artery disease, Gower said, noting that excess visceral, or intra-abdominal, fat raises the risk of these diseases.

Gower and her colleagues conducted the study, with funding from the National Institutes of Health, in 69 overweight but healthy men and women. Subjects received food for two consecutive eight-week periods: first a weight maintenance intervention, and then a weight loss intervention, which cut the number of calories that each person ate by 1,000 each day.

Subjects received either a standard lower-fat diet or a diet with a modest reduction in carbohydrates, or carbs, but slightly higher in fat than the standard diet. The moderately carb-restricted diet contained foods that had a relatively low glycemic index, a measure of the extent to which the food raises blood glucose levels. This diet consisted of 43 percent calories from carbohydrates and 39 percent calories from fat, whereas the standard diet contained 55 percent of calories from carbohydrates and 27 percent from fat. Protein made up the other 18 percent of each diet.

At the beginning and end of each study phase, the researchers measured the subjects' fat deep inside the abdomen and their total body fat using computed tomography (CT) and dual-energy x-ray absorptiometry (DXA) scans.

After the weight maintenance phase, subjects who consumed the moderately carb-restricted diet had 11 percent less deep abdominal fat than those who ate the standard diet. However, when the researchers analyzed results by race, they found it was exclusive to whites. Whites have more deep abdominal fat than Blacks even when matched for body weight or percent body fat, and may benefit from loss of this metabolically harmful depot, Gower said.

During the weight loss phase, subjects on both diets lost weight. However, the moderately carb-restricted diet promoted a 4 percent greater loss of total body fat, Gower said. For individuals willing to go on a weight-loss diet, a modest reduction in carbohydrate-containing foods may help them preferentially lose fat, rather than lean tissue, she said. The moderately reduced carbohydrate diet allows a variety of foods to meet personal preferences.

Hormone test predicts ovarian function after chemotherapy for breast cancer

Sun, 05 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A test that shows how many eggs a woman has in her ovaries may help young women with breast cancer know what their reproductive function will be after chemotherapy, a new study finds. The results will be presented Sunday at The Endocrine Society's 93rd Annual Meeting in Boston.

Called the anti-Mullerian hormone (AMH) test, this blood test measures levels of an ovarian hormone that reflects the size of the ovarian reserve, or remaining egg supply. Currently, doctors use it to quantify a woman's ovarian reserve before in vitro fertilization treatments. Now researchers from Scotland have found that measurement of AMH indicates how likely it will be for a woman to still have eggs in her ovaries after chemotherapy, which can often damage a woman's eggs and cause infertility.

Future reproductive function is a concern for many young women with cancer, said lead investigator Richard Anderson, MD, PhD, professor of clinical reproductive science at the University of Edinburgh. This test will be of benefit to women with newly diagnosed cancer to help decide whether they need to take steps to preserve their fertility.

In the U.S. alone, breast cancer is diagnosed in more than 25,000 women younger than 45 each year, according to the American Cancer Society.

For this study, Anderson and his colleagues recruited 50 premenopausal women, ages 29 to 51, who had just received a diagnosis of early breast cancer. All women had normal menstrual cycles and were asked to keep a daily record of their menstrual cycle, as an index of ovarian activity, during the two years of the study. Before the women started chemotherapy, they gave blood samples for AMH testing. They again had AMH tests one and two years after starting treatment.

Before chemotherapy the median AMH level was 0.4 nanograms per milliliter (ng/mL). After cancer treatment the AMH level fell rapidly, becoming undetectable (below 0.16 ng/mL) in 68 percent of the women after one cycle of chemotherapy, the authors reported. By one-year follow-up, 11 women withdrew from the study, mostly because of cancer recurrence, Anderson said. Menstrual records were available for 39 women at one year and for 29 women at two years.

A low AMH measurement before treatment correlated well with amenorrhea, or absence of menstruation, after treatment. Women whose AMH before treatment was low (below 0.4 ng/mL) were 16 times likelier to have stopped menstruating after chemotherapy than women with a high pretreatment AMH value, Anderson said. The odds of losing ovarian function remained higher even after statistical analysis controlled for increasing age, which tends to lower AMH levels. Women whose AMH before chemotherapy exceeded 0.92 ng/mL were reportedly almost five times more likely to continue menstruating after treatment.

Our data suggest that the AMH test, taken before cancer treatment, can help individualize a woman's infertility risk after chemotherapy for breast cancer, Anderson said.

He added that results of this study, which was funded by the U.K. Medical Research Council, are likely to apply to other types of cancer as well.

Calorie-burning brown fat is a potential obesity treatment, researchers say

Sun, 05 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A new study suggests that many adults have large amounts of brown fat, the good fat that burns calories to keep us warm, and that it may be possible to make even more of this tissue.

The study's lead author, Aaron Cypess, MD, PhD, will present the results Sunday at The Endocrine Society's 93rd Annual Meeting in Boston.

We are now even more optimistic that brown fat could be used for treating obesity and diabetes, said Cypess, an assistant professor at Harvard Medical School and the Joslin Diabetes Center in Boston.

Cypess heads the research team that two years ago published a study showing that brown fat is present in adults, not just in infants and small mammals, as scientists had thought. Although most adult fat is calorie-storing white fat, most adults have some brown fat in an area extending from the front of the neck to the chest, he reported at The Endocrine Society's meeting in 2009.

Now they have learned that brown fat cells lie in deeper fat, not superficial fat, and that the number of regions of brown fat varies by person, Cypess reported. They discovered this by measuring the expression of a protein found exclusively in brown fat, called uncoupling protein-1. However, even in those regions where many brown fat cells are present, they are mixed with white fat cells.

It's a marbling at the cellular level, Cypess said. We wondered: Wouldn't it be nice if you could grow more brown fat? The answer is yes.

In their new study, the researchers succeeded in growing mature human brown fat cells from preadipocytes, or pre-fat cells, that they obtained from a fresh sample of brown fat taken from the neck of a patient having routine surgery. The process took about two weeks in a laboratory dish but likely occurs more quickly in the body, Cypess said.

Some of these preadipocytes may have the choice to become either white or brown fat, he said.

In another experiment, Cypess and his colleagues measured how many calories brown fat burns. To do so, they measured the fat cells' oxygen consumption rate in both cultures and surgical tissue samples from volunteers.

We demonstrated that brown fat burns up a substantial number of calories, Cypess said. We have an organ in our body whose job it is to generate heat and burn calories.

Although Cypess said stimulating the growth of additional brown fat may be a promising treatment of obesity, it cannot replace traditional approaches such as diet and exercise. He said, As powerful as brown fat could be at burning calories, we can easily out-eat the benefit.

Stem cell treatment may become option to treat nonhealing bone fractures

Sun, 05 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Stem cell therapy enriched with a bone-regenerating hormone, insulin-like growth factor-I (IGF-I), can help mend broken bones in fractures that are not healing normally, a new animal study finds. The Endocrine Society's 93rd Annual Meeting will host presentation of the results on Sunday in Boston.

A deficiency of fracture healing is a common problem affecting an estimated 600,000 people annually in North America, according to the principal investigator, Anna Spagnoli, MD, associate professor of pediatrics and biomedical engineering at the University of North Carolina at Chapel Hill.

This problem is even more serious, Spagnoli said, in children with osteogenesis imperfecta, or brittle bone disease, and in elderly adults with osteoporosis, because their fragile bones can easily and repeatedly break, and bone graft surgical treatment is often not successful or feasible

Fractures that do not heal within the normal timeframe are called non-union fractures. Using an animal model of a non-union fracture, a knockout mouse that lacks the ability to heal broken bones, Spagnoli and her colleagues studied the effects of transplanting adult stem cells enriched with IGF-I. They took mesenchymal stem cells (adult stem cells from the bone marrow) of mice and engineered the cells to express IGF-1. Then they transplanted the treated cells into knockout mice with a fracture of the tibia, the long bone of the leg.

Using computed tomography (CT) scanning, the researchers showed that the treated mice had better fracture healing than did control mice either left untreated or treated only with stem cells. They found that the stem cells enriched with IGF-I became bone cells and helped the cells in the broken bones to repair the fracture, speeding the healing. Compared with controls left to heal on their own, treated mice had more bone bridging the fracture gap, and that new bone was three to four times stronger, according to Spagnoli.

More excitingly, we found that stem cells empowered with IGF-I restored the formation of new bone in a mouse lacking the ability to repair broken bones. This is the first evidence that stem cell therapy can address a deficiency of fracture repair, she said.

This success in an animal model of fracture non-union, Spagnoli said, is a crucial step toward developing a stem cell-based treatment for patients with fracture non-unions.

We envision a clinical use of combined mesenchymal stem cells and IGF-1 similar to the approach employed in bone marrow transplant, in which stem cell therapy is combined with growth factors to restore blood cells, she said. I think this treatment will be feasible to start testing in patients in a few years.

IGF-I is approved for treatment of children with a deficiency of this hormone, causing growth failure.

Athletic girls more likely to have impaired bone structure if menstrual cycle stops

Sun, 05 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Young female athletes who have stopped menstruating have a weakening in the quality of their bone structure that may predispose them to breaking a bone, despite getting plenty of weight-bearing exercise, a new study finds. The results will be presented Sunday at The Endocrine Society's 93rd Annual Meeting in Boston.

Given the high number of young women and girls involved in athletic activities and the fact that up to 24% of young female athletes may lose their periods, this finding represents a significant public health concern, said Madhusmita Misra, MD, the study's principal investigator.

Misra, a pediatric endocrinologist at Massachusetts General Hospital in Boston, said amenorrhea, or absence of menstruation, can result from intense physical activity, either alone or combined with inadequate intake of calories. In a previous study, Misra found that athletes who lose their periods have low bone density, a risk factor for fracture and premature osteoporosis. Because abnormal bone structure (microarchitecture) is a known independent risk factor for fractures among older women, she assessed it in the current study.

Misra and her colleagues studied 34 endurance athletes, ages 15 to 21, all of whom were involved in running or other weight-bearing activities. Sixteen athletes had no periods, and 18 had normal menstruation. The investigators studied the athletes' bone density and bone microarchitecture, and compared these measures with those from 16 nonathletic controls. To assess bone structure, they used a form of CT scanning called high-resolution peripheral quantitative computed tomography.

They found that nonmenstruating athletes have a bone structure that is abnormal compared with menstruating athletes and nonathletes. Differences were seen in cortical bone (the outer rim of compact bone) and in trabecular (spongy) bone at both sites studied: the tibia, or shinbone, and even a non-weight-bearing site, one of the long forearm bones near the wrist. Athletes who still got their menstrual periods did not have impaired bone structure, the researchers reported.

Our results are of particular concern to teenagers and young women, who are at a time in their lives when they should be actively accumulating bone and optimizing peak bone mass, she said.

Peak bone mass, the amount of bone present at the end of skeletal maturity, is usually achieved by the mid-20s and is an important factor in determining future bone health.

The study, which was funded by the National Institute of Child Health Development, also found that later age at starting menstruation was associated with a greater chance of bone structure impairments.

Bone microarchitecture may provide information regarding bone health independent of bone mineral density, Misra said. Your bone density score may not reveal the full risk of poor bone strength.

Targeted cancer therapy kills prostate tumor cells

Sun, 05 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A new targeted therapy for prostate cancer halts tumor growth in animals with advanced prostate cancer that is resistant to hormone therapy, a new study finds. The results will be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

This targeted therapy may provide a treatment breakthrough that will extend the lives of men with advanced, hormone-refractory prostate cancer, said lead investigator Shuk-mei Ho, PhD, chairwoman of the Department of Environmental Health at the University of Cincinnati.

Men with prostate cancer that has recurred or has spread outside the prostate routinely receive androgen deprivation therapy, which blocks the action of the male hormones. This castration occurs through surgical removal of both testes or more often with medications. Although effective, this hormone-blocking treatment eventually stops working in some patients, Ho said.

These patients are left with very few treatment options and usually succumb quickly to the disease, she said.

Ho's team previously found they can inhibit the growth of prostate cancer cell lines in culture by targeting and activating a protein called G protein-coupled receptor 30 (GPR30) using the experimental drug G-1, a GPR30 agonist, or stimulator.

In their new study, funded by the Veterans Affairs and the National Institutes of Health, Ho and her co-workers tested G-1 in an animal model of castration-resistant prostate cancer. They implanted human prostate cancer cells beneath the skin of male mice. The established tumor regressed upon castration and after the cancer relapsed, they injected the mice with a low dose of G-1. They also gave G-1 to noncastrated, or intact, male mice that had prostate tumors. In these intact mice that still had male hormones, G-1 did not stop growth of the prostate tumors or cause substantial death of tumor cells (necrosis), they found.

Surprisingly, G-1 was highly effective in halting the growth of the tumors that re-emerged after castration, Ho said.

The castration-resistant tumors showed a 65 percent necrosis. These mice had increased expression of GPR30 after castration, which Ho believes sensitized prostate tumors to the cell growth-inhibiting effects of G-1.

These results mean G-1 won't work without androgen deprivation therapy, she said.

Therefore, Ho reported, the window of time when this targeted therapy might be effective for treating hormone-resistant prostate cancer is after androgen deprivation therapy. She said she believes G-1 can make androgen blockade more effective. G-1 caused no harm to the prostate or other vital organs in mice, she added.

Although GPR30 may have a role in cell growth in female tissues, Ho said it appears to have the opposite effect in men with hormone-resistant prostate cancer. The beauty of this GPR30 is that it does not have any estrogen, and so it will not cause any side effects of estrogen, she said.

Anorexic girls have increased bone density after physiological estrogen treatment

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Estrogen therapy improves low bone density due to anorexia nervosa in teenage girls with the disease when given as a patch or as a low oral dose that is physiological (close to the form or amount of estrogen the body makes naturally). These results of a new study are being presented Monday at The Endocrine Society's 93rd Annual Meeting in Boston.

A large proportion of adolescents with this eating disorder have low bone density and therefore are at an increased risk of fractures, said Madhusmita Misra, MD, the study's lead author and an associate professor of pediatrics at Harvard Medical School and Massachusetts General Hospital in Boston. An important cause of this low bone density is low levels of estrogen, a hormone in the body that prevents bone loss.

Previous studies have shown that giving oral estrogen combined with progesterone as birth control pills is not effective in increasing bone density in girls with anorexia nervosa, Misra said. However, the impact of giving estrogen in a more natural, or physiological, form has not been previously studied in girls with anorexia nervosa.

This National Institutes of Health-funded study explored, over an 18-month period, the effect of physiological estrogen replacement on bone accrual rates in 110 female patients with anorexia nervosa. These patients and 40 healthy-weight girls as controls were between ages 12 to 18 years, a common time for anorexia nervosa to start and also an important time for building optimal bone mass, Misra said.

Girls with anorexia nervosa were randomly assigned to receive either a placebo (an inactive substance) or one of two types of estrogen based on their bone maturity. The researchers estimated bone maturity (whether growth plates had closed) based on wrist and hand X-rays. Those girls with mature bone received either placebo or a full adult dose of estrogen (100 micrograms of estradiol) given via a skin patch. This transdermal form is a natural form of estrogen, Misra said. Girls receiving estrogen also received cyclic progesterone pills to reduce the risk of endometrial cancer.

Girls with anorexia nervosa whose bones were immature received incremental low doses of oral estrogen, ranging from 3.75 to 11.25 micrograms of estradiol. These low, natural levels mimic estrogen levels seen in early puberty and avoid accelerating fusion of the growth plates, which would otherwise limit height potential, Misra said. Healthy-weight controls received no treatment other than calcium and vitamin D supplements, which all subjects received.

Using dual-energy X-ray absorptiometry (DEXA) bone density scans, the researchers assessed bone mineral density at the lumbar spine (lower back), hip and whole body. Physiological estrogen administration caused a significant increase in bone density at the spine and hip, compared with placebo, as found on DEXA Z-scores, the authors reported. However, Misra said that estrogen did not result in a complete catch-up to normal bone density measures. Girls with anorexia nervosa still had lower bone density than healthy-weight controls did.

In addition to weight gain, physiological estrogen could be a potential therapeutic option for optimizing bone mass in girls with anorexia nervosa, Misra said. The decision to treat would depend on the individual patient and her fracture risks.

Fetal programming of disease risk to next generation depends on parental gender

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Overexposure to stress hormones in the womb can program the potential for adverse health effects in those children and the next generation, but effects vary depending on whether the mother or father transmits them, a new animal study suggests. The results will be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

This research sheds light on how babies who are exposed in the womb to excessive levels of stress hormones, known as glucocorticoids, can pass on the health effects to their own children, and how the effects vary between mothers and fathers, said the study's principal investigator, Amanda Drake, MD, PhD, a senior clinical fellow at the University of Edinburgh in Scotland.

Glucocorticoid levels may become raised during pregnancy if, for example, the mother experiences stress or illness or receives glucocorticoid drugs for treatment of illness or premature labor. Excess glucocorticoid exposure of the fetus can reduce birth weight and raise blood pressure later in life in animals and humans, and babies born with low birth weight are at increased risk of diabetes and heart disease in adulthood, Drake said.

This has led to the concept of fetal programming, suggesting that the environment experienced in the womb can affect development, resulting in an increased risk of later disease. This increased disease risk can be passed to the next generation, Drake said.

Using a rodent model of early life programming, Drake and colleagues studied the effects of glucocorticoid overexposure, with the drug dexamethasone, during the last week of gestation. They studied the effects on the directly exposed offspring and on their offspring. Their prior research showed that the low birth weight induced by prenatal exposure to dexamethasone transmits to a second generation through both male and female rats, according to Drake.

This new research showed that although birth weight is reduced in the offspring of male or female rats that were exposed to dexamethasone during fetal development, this effect was more pronounced in the offspring of male rats exposed to excess glucocorticoids during development in the womb.

Additionally, although birth weight was reduced in the second generation of rats, the genes that were affected differed from those seen in their parents, Drake said. In the first generation, glucocorticoid overexposure in the womb affected genes in the liver of the fetus and in the placenta. This increased the likelihood of the baby rats having a low birth weight and increased their risk of developing diabetes and heart disease in later life, she said.

However, the genes affected in the second generation depended on whether the mother or the father had been exposed to glucocorticoids while developing in the womb, the authors reported. These affected genes that could produce adverse health effects included genes important in growth and the transport of nutrients across the placenta.

Regarding the study, which was funded by the U.K. Medical Research Council, Drake said, It could help inform future research to find interventions that could prevent diseases such as diabetes and high blood pressure, Drake said.

Hormone deprivation therapy for prostate cancer may raise diabetes risk

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Men with prostate cancer are at higher risk of developing diabetes or diabetes risk factors if they receive androgen deprivation therapy (ADT) to block the production or action of male hormones that can fuel the growth of this cancer. The results of this new study on the second-most common cancer in men are being presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

These patients may benefit from counseling, screening and closer monitoring for the development of these complications, said the study's lead author, Maria Luisa Cecilia Rivera-Arkoncel, MD, a fellow at the Philippine General Hospital in Manila.

This study adds to the scientific evidence that ADT may increase the chance of diabetes. Sometimes called medical or surgical castration, ADT is a common treatment when prostate cancer has spread outside the prostate. It can be permanent by surgically removing both testicles (bilateral orchiectomy), or, more often, temporary by using medications, such as gonadotropin-releasing hormone (GnRH) agonists, to prevent the testes from making testosterone.

In their study, Rivera-Arkoncel and her colleagues compared 38 men with prostate cancer who received ADT and 36 men with less advanced prostate cancer who did not receive hormonal therapy. Men in the ADT group either underwent bilateral orchiectomy at least six months earlier or received six or more months of treatment with injections of GnRH agonists. Both groups received treatment at the Philippine General Hospital from 2004 to 2010. Although the average age of the two groups was not the same at the beginning of the study, the groups were similar in terms of other diabetes risk factors, Rivera-Arkoncel said.

Based on a review of medical records, the researchers identified patients with Type 2 diabetes or the metabolic syndrome. This syndrome is a cluster of metabolic risk factors that increase the chance of developing diabetes, heart disease and stroke. The criteria used for diagnosis include a large waistline plus two of the following: low HDL (good) cholesterol, high triglycerides (fats in the blood), high blood pressure and high blood sugar.

Men in the ADT group had a twofold increased probability of having diabetes after ADT, compared with the non-ADT group, Rivera-Arkoncel reported. According to the data, the prevalence of diabetes was 42 percent in the ADT group and 19 percent in the other group. In addition, the group receiving ADT had a higher prevalence of the metabolic syndrome than the non-ADT group did: 37 percent versus 28 percent, respectively.

An increased risk of diabetes with ADT has not previously been demonstrated in the Filipino population, which already has a high prevalence of diabetes, she said.

She cautioned, however, that their cross sectional analytical study suggests, but cannot prove, that ADT is the cause of the increased prevalence of diabetes in men who received this hormonal therapy.

Fat burning increases in men with oral form of bronchodilator drug, formoterol

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Formoterol, a medication used to treat asthma and other lung diseases, improves fat burning and protein metabolism in men, a new study finds. The results will be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

Research in animals has shown that formoterol can stimulate the growth of muscle and the burning of fat. This is the first study demonstrating the beneficial metabolic effects of formoterol in humans, said the study's lead author Paul Lee, MD, PhD, a research fellow at the Garvan Institute of Medical Research in Sydney.

The discovery is important, Lee said, because it suggests that formoterol may be used in the future to prevent obesity and muscle loss in humans.

With funding from the National Health Medical Research Council Australia, Lee and colleagues studied the drug in eight healthy men over one week. All men had a healthy weight and received a low daily dose of formoterol in a pill, Lee said. To find the optimal dose, the authors studied three doses in four of the men: 80, 160 or 320 micrograms per day. He said they found that the 160-microgram dose had metabolic benefits without raising heart rate.

All eight men underwent metabolic testing before and after treatment with 160 micrograms daily of formoterol. One week of formoterol treatment increased metabolism in the men by more than 10 percent, according to an estimate of the resting energy expenditure (the calories needed at rest during 24 hours). The rate of fat oxidation, or burning, rose by almost 25 percent, indicating there may be a loss of fat in the long term, Lee reported.

Additionally, the researchers determined the rate of protein burning before and after treatment.

Protein is the building block for muscle in the body, Lee explained. Burning less protein means preservation of muscle and may increase muscle mass in the long term.

After formoterol treatment the protein burning rate fell close to 15 percent, he said. They used the leucine turnover technique, which tracks the synthesis and breakdown of the amino acid leucine. According to Lee, it is the most accurate method of estimating protein metabolism in humans.

Lee said none of the volunteers reported any major side effects from the 160-microgram dose. Tachycardia, or fast heart rate, is a known side effect of older medications in the same drug class as formoterol, especially at high doses. Low dose formoterol, similar to the one used in this clinical study, resulted in no substantial adverse cardiac effects in animal studies, he said.

Our results call for further research to investigate whether formoterol improves body composition, physical health and function, Lee said.

Topiramate may have benefit as a weight-loss drug

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The drug topiramate can help people lose weight as long as they can tolerate the side effects, according to authors of a new study that reviewed the medical literature. Brazilian researchers will present the results Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

Among more than 3,300 overweight or obese patients, those who took topiramate for at least four months lost 11.8 pounds more on average than individuals who took dummy pills, or placebo, found the meta-analysis, a systematic and quantitative review of published studies.

Topiramate is not an approved drug for the treatment of obesity. Data from individual clinical trials might not be sufficient to support physicians' decision to prescribe it for this use, and robust evidence of its safety is lacking, said lead investigator Caroline Kramer, MD, PhD. She is an endocrinologist at Clinic Hospital of Porto Alegre in Brazil.

Currently topiramate is approved as an anti-convulsant for treatment of seizure disorders and for prevention in adults of migraine headaches.

The investigators pooled the research results of 10 randomized, controlled clinical trials (considered the gold standard in scientific research) that evaluated the benefits and adverse effects of topiramate prescribed for weight loss. They analyzed data about the effectiveness of topiramate on weight loss in 3,320 patients and data on adverse effects in 6,620 patients, she said.

According to the analysis, the duration and dosage of treatment affected the weight-loss benefits. Weight loss was higher when the drug was prescribed at doses of 96 to 200 milligrams per day for more than 28 weeks compared with less than 28 weeks, the authors reported. Compared with study subjects who took the placebo, topiramate-treated patients were seven times likelier to lose more than 10 percent of their body weight.

However, the authors found that patients were nearly two times more likely to stop topiramate treatment because of side effects than were those receiving placebo. The most common side effects, according to Kramer, included a burning sensation (paresthesia), typically around the mouth; impaired taste; and psychomotor disturbances, including slower thinking and reduced physical movements. Difficulty concentrating and memory impairment also were increased.

Topiramate has a substantial effect on weight loss, at least comparable to the weight loss that other anti-obesity drugs induce, Kramer said. We have so few pharmacological options for the treatment of obesity that I believe topiramate can be a useful tool together with diet and exercise.

She said it is important, however, for patients to understand the drug's known possible side effects and to be aware that it may have uncommon side effects that researchers have not yet observed.

The National Institutes of Health caution that people should use prescription weight-loss medications only if they are at increased risk of health problems because of their excess weight.

Gene therapy reverses type 1 diabetes in mice

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) An experimental cure for Type 1 diabetes has a nearly 80 percent success rate in curing diabetic mice. The results, to be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston, offer possible hope of curing a disease that affects 3 million Americans.

With just one injection of this gene therapy, the mice remain diabetes-free long term and have a return of normal insulin levels in the body, said Vijay Yechoor, MD, the principal investigator and an assistant professor at Baylor College of Medicine in Houston.

Yechoor and his co-workers used their new gene therapy in a nonobese mouse model of Type 1 diabetes. The therapy attempts to counter the two defects that cause this autoimmune form of diabetes: autoimmune attack and destruction of the insulin-producing beta cells by T cells. First, the researchers genetically engineer the formation of new beta cells in the liver using neurogenin3. This gene defines the development of pancreatic islets, which are clusters of beta cells and other cells. Along with neurogenin3, they give an islet growth factor gene called betacellulin to stimulate growth of these new islets.

The second part of the therapy aims to prevent the mouse's immune system from killing the newly formed islets and beta cells. Previously the research team combined neurogenin3 with the gene for interleukin-10, which regulates the immune system. However, with that gene, they achieved only a 50 percent cure rate in diabetic mice, Yechoor said.

In the new study, the investigators added a gene called CD274 or PD-L1 (programmed cell death 1 ligand-1). It inhibits activity of the T cells only around the new islets in the liver and not in the rest of the body, he explained.

We want the gene to inactivate T cells only when they come to the new islet cells. Otherwise, the whole body would become immunocompromised, Yechoor said.

This treatment reversed diabetes in 17 of 22 mice, or 78 percent. Diabetic mice that otherwise live only six to eight weeks were growing normally and were free of diabetes as long as 18 weeks after injection of the gene therapy, Yechoor said.

This treatment approach, he said, has the potential to be a curative therapy for Type 1 diabetes.

The other mice reportedly responded to the gene therapy initially but then became diabetic again. There are two possibilities, according to Yechoor, why the therapy did not achieve a 100 percent cure rate.

T cells are the predominant part of islet destruction, but other pathways, including beta cells could also contribute, meaning we would need to target those pathways as well, Yechoor said. Or maybe the efficiency of this new protective gene is not sufficient, and we need to give a larger dose.

BUSM names Deborah Frank, M.D., inaugural professors in child health and well-being

Wed, 01 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Boston University School of Medicine (BUSM) announces the establishment of an endowed Professorship in Child Health and Well-Being in the department of Pediatrics. This anonymously donated endowment reinforces the importance of supporting clinical practice focusing on public policies related to ending hunger and hardship in young children.

The inaugural incumbent of this professorship is Deborah A. Frank, MD. Frank serves as BUSM professor of Pediatrics; director, Grow Clinic for Children at Boston Medical Center (BMC); and founder and principal investigator of Children's HealthWatch, a network of pediatric and public health researchers working to improve child health. A highly respected national authority, she has testified before both the United States and Massachusetts legislatures on the growing national problem of hunger and its effects on children. Frank also leads research funded by the National Institute on Drug Abuse on the effects of intrauterine exposure to cocaine and other substances on children's long term development. She advocates at hearings and in the media against criminalizing addicted mothers or stigmatizing their children.

Frank has served on numerous committees and advisory boards including the Mayor's Hunger Commission, the Massachusetts Child Hunger Initiative and the Physicians Task Force on Childhood Hunger in Massachusetts. She has received awards in recognition for her work including the 2004 Standing Ovation Award, Massachusetts Human Services Coalition; 2007 Woman of Valor Award, Jewish Funds for Justice; 2008 Woman of Justice Award, Boston Lawyer's Weekly, and more recently in 2010 Dr. Frank received the Massachusetts Health Council Outstanding Leadership Award and the Physician Advocacy Merit Award from the Institute on Medicine as a Profession at Columbia University. Frank is the author of more than 50 papers and articles.

An endowed professorship is one of the most significant means by which BUSM can honor its highly esteemed teachers and researchers. They are important to the mission of BUSM because they offer our school the opportunity to attract highly distinguished faculty, said BUSM Dean Karen H. Antman, MD. Dr. Frank's long-standing commitment to caring for and training others to care for children and to understanding and preventing child hunger makes her a deserving candidate to be the first to hold this professorship. By selecting Dr. Frank for this important honor we show continued commitment to serving the most basic needs of the youngest and most vulnerable members of our society.

A summa cum laude graduate of Radcliffe College and Harvard Medical School, Frank did her residency at Children's Orthopedic Hospital in Seattle and completed a fellowship in Child Development with T. Berry Brazelton at Children's Hospital in Boston. She joined BUSM as a clinical assistant professor of Pediatrics in 1981 when she also established the Failure to Thrive Program at Boston City Hospital, now known as the Grow Clinic for Children at Boston Medical Center (BMC). Frank was named BUSM professor of Pediatrics in 2001.

BD nano pen needle - World's smallest insulin injection needle launched

Wed, 25 May 2011 16:47:19 PST

( from http://www.rxpgnews.com ) The world's smallest pen needle insulin injection for diabetics promising relief from pain was launched here Wednesday, said a statement from its manufacturer Becton, Dickinson and Company -.

'The BD nano pen needle is proven to be as effective as the longer needles in patients of all body types and proven to offer a less painful injection experience for people with diabetes who inject insulin. This is the world's first four mm long pen needle,' said Diwakar Mittal, business manager, BD Medical-Diabetes Care, India.

The needle is four mm in length and of 32 gauge thickness making it the shortest and the thinnest in the market.

Currently, insulin injection needles are available in variable sizes of which the five mm long needles are the most common among diabetics.

'We are confident that this tiny needle can have a big impact by easing diabetes patients' transition and ongoing adherence to injectable drug therapy regimens,' Mittal added.

'The pen needle provides equivalent glucose control as compared to longer insulin pen needles. It effectively delivers an insulin dose to the layer of fat below the skin which is the recommended site for insulin injections,' the statement said.

CHOP partners with Vascular Magnetics, Inc. to pursue commercial potential of blood vessel research

Mon, 09 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Building on its extensive laboratory research using magnetically guided nanoparticles to deliver drugs to diseased blood vessels, The Children's Hospital of Philadelphia has just spun off its first startup company, Vascular Magnetics, Inc. (VMI).

By licensing its technology to VMI, a new company formed to develop the lab findings into a commercially viable therapy, the Hospital aims to create a novel, greatly needed treatment for peripheral artery disease (PAD). Characterized by blocked arteries, primarily in the legs, PAD affects more than 27 million older adults in North America and Europe, with diabetes patients and smokers at particularly high risk. Current treatments for PAD, including drug-eluting stents, are ineffective, with re-blockage of the arteries occurring at a high rate.

In addition to being the Hospital's first startup company, the program targets patients outside the Hospital's usual pediatric age group. While our first target group is adult patients, the technique represents a new platform technology, potentially adaptable to delivering a variety of therapies to children as well as adults, says the technology's inventor, Robert J. Levy, M.D., the William J. Rashkind Endowed Chair in Pediatric Cardiology at The Children's Hospital of Philadelphia.

Levy co-founded VMI with Richard S. Woodward, Ph.D., the company's Chief Executive Officer. The two first joined forces through the QED Proof-of-Concept Program sponsored by the University City Science Center in West Philadelphia. The goal of the QED Program, the nation's first multi-institutional proof-of-concept program for life sciences technologies, is to accelerate research from academic laboratories into the marketplace. A unique feature of this program is that academic scientists such as Levy are partnered with experienced business advisors such as Woodward, who has a background that includes developing nanoparticles and polymeric coatings.

The Science Center is proud to have played a role in the launch of Vascular Magnetics, said Stephen S. Tang, Ph.D., MBA, president and CEO of the University City Science Center. VMI's launch is helping to prove our concept that the early addition of business advice is a key element of the tech transfer puzzle.

In a series of animal studies over the past decade, Levy and his team at Children's Hospital have investigated his new approach to stent-based therapy. They have developed nanoparticles, extremely tiny spheres made of a biodegradable polymer impregnated with iron oxide. Under a low-power, uniform magnetic field, much lower than that produced by existing MRI machines, magnetic forces drive the nanoparticles into metal stents and the surrounding artery. The nanoparticles carry a therapeutic payload of the drug paclitaxel, which is released into the surrounding blood vessel tissue in order to slow arterial re-blockage. In 2008, Forbes magazine named Levy's work a promising disruptive technology, one that might eventually supplant conventional technology, in this case, drug-eluting stents.

As they advance the technique to human trials, Levy and Woodward envision a future therapy called Vascular Magnetic InterventionTM which would serve as an adjunct to artery stenting. A physician would open and stent the blocked artery and then insert a catheter tipped with an expandable magnetic targeting device. The targeting device would be expanded against the walls of the artery.

A magnetic field is then applied to the leg, and paclitaxel-containing magnetic nanoparticles would be administered through the catheter. The targeting device develops strong magnetic gradients that force the nanoparticles into the wall of the artery. After treatment and removal of the catheter, the wall of the artery is uniformly coated with the nanoparticles, which slowly biodegrade and release the drug. The uniform coating provides a higher dose of drug than is achievable with a drug-eluting stent. In addition, the technique could be used to re-treat arteries where the stents have become re-blocked.

The technology, said Levy, is highly adaptable. Instead of paclitaxel, it could deliver other therapeutic compounds, DNA for site-specific gene therapy, therapeutic cells, or other treatments. In addition to treating PAD, the technique might carry paclitaxel to narrowed coronary arteries, chemotherapy drugs to a tumor, or other medications to a bile duct or a urinary tract. Eventually, said Levy, the technology could be applied to types of pediatric heart disease, such as primary pulmonary hypertension or heart defects.

As its lab research continues, Vascular Magnetics is moving ahead to attract venture capital. Our plan is to prove the efficacy of this therapy in humans by late 2015, said Woodward. The revenue projections for the company suggest sales of over a billion dollars per year within about four years after commercial launch.

Bariatric surgery highly cost-effective treatment for type 2 diabetes in the obese

Tue, 29 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (March 29, 2011) -- Bariatric surgery is an especially cost-effective therapy for managing Type 2 diabetes in moderately and severely obese patients. These findings and others were presented today at the 2nd World Congress on Interventional Therapies for Type 2 Diabetes, hosted by NewYork-Presbyterian Hospital and Weill Cornell Medical College.

Cost effectiveness is central to the larger issue of access to surgical treatment of diabetes, says Dr. Francesco Rubino, director of the Congress and director of gastrointestinal metabolic surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

Today, an estimated 285 million people around the globe suffer from Type 2 diabetes, and the number is expected to double by 2030, notes Dr. Rubino, who also serves as associate professor of surgery at Weill Cornell Medical College. The need for effective, potentially curative therapies is urgent.

According to an analysis presented today at the Congress by an Australian researcher, bariatric surgery to treat Type 2 diabetes has been demonstrated to be very cost effective in the countries in which this research has been done -- the United States, United Kingdom, Australia, and in some European settings.

The review also found that several studies have determined that bariatric surgery was not only cost effective, but cost saving, says Catherine Keating, a senior research fellow from the Health Economics Unit at Deakin University in Melbourne, who made the presentation. For obese patients diagnosed with Type 2 diabetes during the two years prior to bariatric surgery, one study found that the upfront costs of surgery would be fully recouped through the prevention of future health care costs to treat Type 2 diabetes. This study was undertaken alongside a clinical trial that found that remission of Type 2 diabetes was five times greater in surgically treated patients, relative to those receiving conventional therapies, she says.

For this patient group bariatric surgery generates both cost savings and health benefits, Ms. Keating says. This provides the strongest rationale yet for implementation of this treatment on economic grounds.

Treatment studies have shown that bariatric surgery, initially developed for the treatment of morbid obesity, can improve or normalize blood sugar levels, reduce or even eliminate the need for medication, and lower the risk of diabetes-related death.

A number of new cost-effectiveness studies have been discussed at the meeting, says Dr. David Reed Flum, who co-chairs the Congress's policy track. As health care costs soar, the obligation of all those involved in this issue is to understand the way resources are currently being applied to the treatment and prevention of diabetes and to explore what the future impact on health care resources might be if surgery becomes a meaningful part of the public health response to the diabetes epidemic, says Dr. Flum, professor of surgery and health services at the University of Washington School of Medicine.

Health ministers, economists, payers and politicians have a critical role in determining the future of this issue, and we expected a robust dialog during this track of the Congress he says.

The studies looked at whether the costs of the surgery -- estimated at between $15,000 and $24,000 in the United States -- are justified by its effectiveness and its potential to save future health care treatment for obesity-related diseases such as Type 2 diabetes.

The effectiveness credentials for bariatric surgery are now very strong. It has been proven to reduce disease, extend life expectancy and improve quality of life, says Ms. Keating. However, in the context of limited health care budgets, authorities around the world state that health care funding should be informed by an assessment of both treatment costs and effectiveness.

To perform her analysis, Ms. Keating examined 16 published studies that looked at the cost-effectiveness of bariatric surgery, including gastric bypass and gastric banding. Ten of those studies examined the procedures in severely obese patients (those whose body mass index, or BMI, is greater than 35) who did not have Type 2 diabetes, and six looked at patients with Type 2 diabetes whose BMI was 30 to 40 (moderately to severely obese).

Each country establishes its own measure of cost effectiveness. In the United States, the threshold for benefit is $50,000 per quality-adjusted life year (QALY), which is defined as a year of human life with some adjustments for disease or disability.

Ms. Keating's review found that bariatric surgery was very cost effective in both populations she studied (patients without diabetes and a BMI over 35, and patients with diabetes and a BMI 30 to 40), but that it was twice as cost effective in the latter category -- the patients with Type 2 diabetes.

This is likely because patients with diabetes have greater ill heath and therefore more benefits can be achieved through surgery in terms of quality of life, life expectancy and prevention of future health care costs, she says. Without treatment, patients with Type 2 diabetes would endure lifelong disease and escalating health care costs.

Among the costs associated with medical management of Type 2 diabetes are treatment for complications that affect the eyes, heart, kidneys and extremities. Long-term costs include outpatient care, prescription medications and diabetes-related hospitalizations and surgeries, including amputations.

The analysis further demonstrated that using surgery to treat patients with newly diagnosed Type 2 diabetes (diagnosed less than five years before surgery) is more cost effective than using the surgery with patients whose diabetes has been established for longer than five years. For example, a 2009 U.S. study found that bypass surgery had cost-effectiveness ratios of $7,000/QALY and $12,000/QALY for severely obese patients with newly diagnosed and established diabetes, respectively.

Targeting recently diagnosed diabetes is likely to be more cost effective because diabetes remission rates achieved are higher in this group than in those with established Type 2 diabetes, Ms. Keating says. Some of the studies I analyzed, particularly those targeting therapy for patients with recently diagnosed Type 2 diabetes, have found that the costs of surgery may be fully recouped through prevention of future health care costs. This excellent result is fairly rare.

Johns Hopkins scientists link DNA 'end-caps' length to diabetes risk

Thu, 24 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) New evidence has emerged from studies in mice that short telomeres or caps at the ends of chromosomes may predispose people to age-related diabetes, according to Johns Hopkins scientists.

Telomeres are repetitive sequences of DNA that protect the ends of chromosomes, and they normally shorten with age, much like the caps that protect the end of shoelaces. As telomeres shorten, cells lose the ability to divide normally and eventually die. Telomere shortening has been linked to cancer, lung disease, and other age-related illnesses. Diabetes, also a disease of aging, affects as many as one in four adults over the age of 60.

The Johns Hopkins research, described in the March 10 issue of PLoS One, arose from scientist Mary Armanios' observation that diabetes seems to occur more often in patients with dyskeratosis congenita, a rare, inherited disease caused by short telomeres. Patients with dyskeratosis congenita often have premature hair graying and are prone to develop early organ failure.

Dyskeratosis congenita is a disease that essentially makes people age prematurely. We knew that the incidence of diabetes increases with age, so we thought there may be a link between telomeres and diabetes, says Armanios, assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center.

Armanios studied mice with short telomeres and their insulin-producing beta cells. Human diabetics lack sufficient insulin production and have cells resistant to its efficient use, causing disruption to the regulation of sugar levels in the blood.

Armanios found that despite the presence of plentiful, healthy-looking beta cells in the mice, they had higher blood sugar levels and secreted half as much insulin as the controls. This mimics early stages of diabetes in humans where cells have trouble secreting insulin in response to sugar stimulus, says Armanios.

Many of the steps of insulin secretion in these mice, from mitochondrial energy production to calcium signaling, functioned at half their normal levels, says Armanios.

In beta cells from mice with short telomeres, they found disregulation of p16, a gene linked to aging and diabetes. No such mistakes were found in the controls.

In addition, many of the gene pathways essential for insulin secretion in beta cells, including pathways that control calcium signaling, were altered in beta cells from mice with short telomeres.

Armanios says that some studies have suggested that diabetic patients may have short telomeres, but it was not clear whether this contributes to diabetes risk or is a consequence of the disease.

Age is the most important risk factor for diabetes, and we also know that family heredity plays a very important role. Telomere length is an inherited factor and may make people more prone to develop diabetes, says Armanios.

Based on this work, Armanios says that telomere length could serve as a biomarker for development of diabetes. Armanios and her colleagues are planning to conduct research to examine whether telomere length can predict the risk of diabetes prospectively.

New gene sites affecting nonalcoholic fatty liver disease discovered

Thu, 10 Mar 2011 05:00:00 PST

( from http://www.rxpgnews.com ) NAFLD is a condition where fat accumulates in the liver (steatosis) and can lead to liver inflammation (nonalcoholic steatohepatitis or NASH) and permanent liver damage (fibrosis/cirrhosis). NAFLD affects anywhere from 11% to 45% of some populations and is associated with obesity, hypertension, and problems regulating serum lipids or glucose.

These findings will help us to better diagnose, manage, and treat NAFLD in the future and help explain why some but not all people with obesity develop particular complications of obesity; some carry genetic variants that predispose them to some but not other metabolic diseases. says lead author Elizabeth K. Speliotes, M.D., Ph.D., M.P.H., an Assistant Professor of Gastroenterology, Internal Medicine, and Computational Medicine and Bioinformatics at the University of Michigan.

Investigators from The Old Order Amish, Age Gene-Environment Susceptibility - Reykjavik Study , Family Heart Study, and Framingham Heart Study, collectively called the GOLD (Genetics of Obesity-related Liver Disease) Consortium meta-analyzed genome wide association data for liver steatosis from 7,126 individuals and then followed up top associating variants in cases of NASH/fibrosis from the NASH-Clinical Research Network that were genetically matched to controls from the MIGen study to find the five variants that reproducibly associate with NAFLD. All the genetic variants found increased fat deposition in the liver. However, only some affected development of inflammation/permanent damage of the liver or development of serum lipid/glucose abnormalities.

Ingrid Borecki, Ph.D., M.S., Associate Professor of Biostatistics and Genetics, co-director of the Division of Statistical Genomics at Washington University School of Medicine in Saint Louis, and senior author on the paper says We found that approximately one quarter of the variation in NAFLD is influenced by genetic factors, and the loci we identified in the study account for about 20 percent of that genetic component. Thus the effects of these variants on NAFLD are substantial and possibly could be incorporated into clinical algorithms in the future to better classify people into risk categories. This work comes at a time when the number of people affected by these liver abnormalities is increasing, along with the prevalence of obesity in our population. Thus it is a growing problem.

Interestingly, the pattern of effects on multiple metabolic traits at two associated loci were identical and the genes closest to the best association signal at these loci are predicted to play a role in subsequent steps in triglyceride breakdown. Triglycerides are the major form of fat stored in the liver in NAFLD. This suggests that defects in triglyceride breakdown may contribute to development of NAFLD.

Through the approaches we undertook in this study we show that we can classify genes into groups, implicating new pathways, not just genes, that affect this disease. This approach can be used to identify pathways that affect other traits as well Speliotes says.

Speliotes notes that identifying variants and ultimately genes that affect NAFLD opens up new avenues for developing novel therapeutics for this condition. Currently, only weight loss and possibly increased physical activity can decrease hepatic steatosis. Getting people to lose weight and increase their physical activity however is a challenge worldwide, which is why obesity has become a global epidemic. This study provides possible new drug targets for therapeutic intervention of NAFLD. Further, our comprehensive examination of the effects of these genetic variants on multiple traits can help guide development of therapeutics against the gene targets of these variants so that we can chose targets that have specific effects on a desired disease while minimizing unwanted side effects.

Trial will test whether surgery is the best option for type 2 diabetes

Thu, 10 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Feb. 10, 2011) -- A new clinical trial at NewYork-Presbyterian Hospital/Weill Cornell Medical Center is among the first to test surgery specifically for Type 2 diabetes. The aim of the study is to understand whether surgery can control diabetes, as well or even better than the best medical treatment available today. This is the first study of its kind open to patients who are overweight or mildly obese.

Under current guidelines, bariatric surgery is only indicated for the treatment of severe or morbid obesity, defined as having a body mass index (BMI) of 35 or greater. By contrast, the new study is open to patients with a BMI as low as 26. Normal-weight individuals have BMI ranging between 19 and 25 and overweight individuals have BMI between 26 and 29, whereas a BMI above 30 defines obesity. Patients with a BMI below 26 and above 35 will not be considered for enrollment in the trial.

Previous research has shown that in severely obese patients (BMI greater than 35) gastric bypass surgery is a safe and effective way to treat Type 2 diabetes. It has been shown to improve or normalize blood glucose levels, reduce or even eliminate the need for medication, and lower the risk for diabetes-related death.

There is preliminary evidence suggesting that that these results are attainable even in overweight or mildly-obese patients, says Dr. Francesco Rubino, chief of the gastrointestinal metabolic surgery program at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and associate professor of surgery at Weill Cornell Medical College.

In support of this belief, recommendations from the American Diabetes Association's January 2009 issue of Standards of Care: Diabetes Care, and from the Diabetes Surgery Summit Consensus Conference, published in the March 2010 issue Annals of Surgery, suggest that randomized clinical trials for the study of surgery in patients with BMI below 35 are priority for diabetes research.

Having a potentially effective surgical option against diabetes does not mean that surgery is the best choice for every diabetic patient, Dr. Rubino adds. We need rigorous, comparative clinical trials, like this one, in order to better understand when to prioritize surgery and when to recommend traditional medical treatment.

The new study is enrolling 50 patients with Type 2 diabetes who will be randomized to receive surgery -- specifically, Roux-en-Y Gastric Bypass -- or traditional medical therapy and intensive lifestyle modification. All patients will be counseled in lifestyle modification techniques like diet and exercise.

Dr. Rubino expects that there will be medical advantages for patients in both arms of the trial since those assigned to the medical arm will receive the most rigorous medical diabetes therapy available. A multidisciplinary team of diabetes and nutrition experts will take care of patients using the most current, approved drugs for diabetes as well as an intensive approach to lifestyle changes. Patients in the medical arm will also be offered the chance to switch study arms and have surgery free of charge after the study is complete, or earlier should their diabetes remain poorly controlled after medical and lifestyle therapy.

Genes of the immune system are associated with increased risk of mental illness

Mon, 07 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Genes linked to the immune system can affect healthy people's personality traits as well as the risk of developing mental illness and suicidal behaviour, reveals a thesis from the University of Gothenburg, Sweden.

Inflammation is part of the immune system and is responsible for defending humans against infection as well as fascilitating the healing of injuries, and is therefore vital for our survival. Research has demonstrated that inflammatory processes also have other roles to play as inflammatory substances produced by the body influence mechanisms in the brain involving learning and memory.

Inflammatory substances produced in moderate quantities in the brain can be beneficial during the formation of new brain cells, for example. However, an increase in the levels of these substances as is the case during illness, can result in damage to the brain.

Previous studies have shown that individuals suffering from various mental illnesses have an increased peripheral inflammation, but the reason behind this increase is not known, says Petra Suchankova Karlsson, who wrote the thesis. It has been suggested that the stress that goes with mental illness activates the body's immune system, but it is also possible that inflammation in the body affects the brain, which in turn results in mental illness.

Previous studies have focused on how environmental and psychological factors affect the immune system's impact on the brain. Suchankova's thesis presents, for the first time, results that suggest that several different genes linked to the immune system are associated with healthy people's personality traits. It also demonstrates that some of these genes are associated with an increased risk of developing schizophrenia or suicidal behaviour.

One of the things we studied was a gene variant that increases impulsiveness in people who carry it, says Suchankova. We already knew that the risk of attempting suicide is higher in impulsive people and therefore analysed this gene variant in a group of patients who had attempted to take their life. We found that these patients more often carried the particular gene variant when compared to the general population which meant that this variant was not only associated with increased impulsiveness in healthy individuals but also with increased risk of suicidal behaviour.

The change in the levels of inflammatory substances in the blood of patients suffering from a mental illness as previously noted may have been caused by inflammation-related genes affecting the risk of mental illness, rather than the illness itself leading to a change in levels, as is traditionally believed.

It could well be that some variants of the genes play a role in the development of mental illness by controlling how the brain is formed, perhaps during the embryonic stage, or by affecting the transfer of signal substances, says Suchankova.

The results of this thesis support the proposed role of the immune system in mental illness, and could be used as a basis for further studies that, it is hoped, will lead to the development of new treatment methods.

The thesis has been successfully defended.

Interaction between fatty acid synthase and nitric oxide synthase key to vascular complications in diabetes mellitus

Sat, 29 Jan 2011 21:46:47 PST

( from http://www.rxpgnews.com ) A key mechanism that appears to contribute to blood vessel damage in people with diabetes has been identified by researchers at Washington University School of Medicine in St. Louis.

Microvascular and macrovascular complications are common in Diabetes mellitus. Many of the nearly 26 million Americans with the disease face the prospect of amputations, heart attack, stroke and vision loss because of damaged vessels.

Reporting in the Journal of Biological Chemistry, the Washington University researchers say studies in mice show that the damage appears to involve two enzymes, fatty acid synthase (FAS) and nitric oxide synthase (NOS), that interact in the cells that line blood vessel walls.

“We already knew that in diabetes there’s a defect in the endothelial cells that line the blood vessels,” says first author Xiaochao Wei, PhD. “People with diabetes also have depressed levels of fatty acid synthase. But this is the first time we’ve been able to link those observations together.”

Wei is a postdoctoral research scholar in the lab of Clay F. Semenkovich, MD, the Herbert S. Gasser Professor of Medicine, professor of cell biology and physiology and chief of the Division of Endocrinology, Metabolism and Lipid Research.

Wei studied mice that had been genetically engineered to make FAS in all of their tissues except the endothelial cells that line blood vessels. These so-called FASTie mice experienced problems in the vessels that were similar to those seen in animals with diabetes.

“It turns out that there are strong parallels between the complete absence of FAS and the deficiencies in FAS induced by lack of insulin and by insulin resistance,” Semenkovich says.

Comparing FASTie mice to normal animals, as well as to mice with diabetes, Wei and Semenkovich determined that mice without FAS, and with low levels of FAS, could not make the substance that anchors nitric oxide synthase to the endothelial cells in blood vessels.

“We’ve known for many years that to have an effect, NOS has to be anchored to the wall of the vessel,” Semenkovich says. “Xiaochao discovered that fatty acid synthase preferentially makes a lipid that attaches to NOS, allowing it to hook to the cell membrane and to produce normal, healthy blood vessels.”

In the FASTie mice, blood vessels were leaky, and in cases when the vessel was injured, the mice were unable to generate new blood vessel growth.

The actual mechanism involved in binding NOS to the endothelial cells is called palmitoylation. Without FAS, the genetically engineered mice lose NOS palmitoylation and are unable to modify NOS so that it will interact with the endothelial cell membrane. That results in blood vessel problems.

Semenkovich
“In animals that don’t have fatty acid synthase and normal nitric oxide synthase in endothelial cells, we saw a lot of leaky blood vessels,” Semenkovich explains. “The mice also were more susceptible to the consequences of infection, and they couldn’t repair damage that occurred — problems that also tend to be common in people with diabetes.”

In one set of experiments, the researchers interrupted blood flow in the leg of a normal mouse and in a FASTie mouse.

“The control animals regained blood vessel formation promptly,” Semenkovich says, “but that did not happen in the animals that were modified to be missing fatty acid synthase.”

It’s a long way, however, from a mouse to a person, so the researchers next looked at human endothelial cells, and they found that a similar mechanism was at work.

“Our findings strongly suggest that if we can use a drug or another enzyme to promote fatty acid synthase activity, specifically in blood vessels, it might be helpful to patients with diabetes,” Wei says. “We also have been able to demonstrate that palmitoylation of nitric oxide synthase is impaired in diabetes, and if we can find a way to promote the palmitoylation of NOS, even independent of fatty acid synthase, it may be possible to treat some of the vascular complications of diabetes.”

And it shouldn’t matter whether a person has type 1 diabetes and can’t manufacture insulin or the more common type 2 diabetes, in which a person becomes resistant to insulin.

“That’s one of the key findings,” Semenkovich says. “It won’t matter whether it’s an absence of insulin or resistance to insulin: both are associated with defects in FAS.”

UCSF study identifies chemicals in pregnant women

Fri, 14 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) The bodies of virtually all U.S. pregnant women carry multiple chemicals, including some banned since the 1970s and others used in common products such as non-stick cookware, processed foods and personal care products, according to a new study from UCSF. The study marks the first time that the number of chemicals to which pregnant women are exposed has been counted.

Analyzing data for 163 chemicals, researchers detected polychlorinated biphenyls (PCBs), organochlorine pesticides, perfluorinated compounds (PFCs), phenols, polybrominated diphenyl ethers (PBDEs), phthalates, polycyclic aromatic hydrocarbons (PAHs) and perchlorate in 99 to 100 percent of pregnant women. Among the chemicals found in the study group were PBDEs, compounds used as flame retardants now banned in many states including California, and dichlorodiphenyltrichloroethane ( DDT), an organochlorine pesticide banned in the United States in 1972.

Bisphenol A (BPA), which makes plastic hard and clear, and is found in epoxy resins that are used to line the inside of metal food and beverage cans, was identified in 96 percent of the women surveyed. Prenatal exposure to BPA has been linked to adverse health outcomes, affecting brain development and increasing susceptibility to cancer later in life, according to the researchers.

Findings will be published in Environmental Health Perspectives on Jan. 14, and now are available on an embargoed basis.

The study was not designed to identify direct connections to adverse health outcomes.

It was surprising and concerning to find so many chemicals in pregnant women without fully knowing the implications for pregnancy, said lead author Tracey Woodruff, PhD, MPH, director of the UCSF Program on Reproductive Health and the Environment.

Several of these chemicals in pregnant women were at the same concentrations that have been associated with negative effects in children from other studies. In addition, exposure to multiple chemicals that can increase the risk of the same adverse health outcome can have a greater impact than exposure to just one chemical, said Woodruff, an associate professor in the UCSF Department of Obstetrics and Gynecology and Reproductive Sciences.

Exposure to chemicals during fetal development has been shown to increase the risk of adverse health consequences, including preterm birth and birth defects, childhood morbidity, and adult disease and mortality according to the research team. In addition, chemicals can cross the placenta and enter the fetus, and in other studies, a number of chemicals measured in maternal urine and serum have been found in amniotic fluid, cord blood and meconium, they state.

The researchers analyzed data for 268 pregnant women from the National Health and Nutritional Examination Survey (NHANES) 2003-2004, a nationally representative sample of the U.S. population.

Our findings indicate several courses of action. First, additional research is needed to identify dominant sources of exposure to chemicals and how they influence our health, especially in reproduction, said Woodruff. Second, while individuals can take actions in their everyday lives to protect themselves from toxins, significant, long-lasting change only will result from a systemic approach that includes proactive government policies.

Silencing the TLR4 gene to stop the cardiovascular disease in diabetic patients

Fri, 10 Dec 2010 08:11:49 PST

( from http://www.rxpgnews.com ) Silencing the TLR4 gene can stop the process which may lead to cardiovascular disease in diabetic patients. Researchers writing in BioMed Central's open access Journal of Translational Medicine carried out a series of in vitro tests which demonstrated that TLR4 plays a critical role in hyperglycaemic cardiac apoptosis, and that silencing the gene using specific small interfering RNA (siRNA) can prevent it.

Wei-Ping Min, from the University of Western Ontario, Canada, worked with a team of researchers to perform the tests in cells taken from diabetic mice. He said, "We found that TLR4 was up-regulated in the myocardia of diabetic mice. Treatment with TLR4 siRNA attenuated the apoptosis seen in these cells, thus highlighting the potential clinical use of siRNA-based therapy".

Min and his colleagues induced hyperglycemia in adult mice by injecting them with streptozotocin, a toxin that poisons insulin-producing beta cells. They found that after 7 days of hyperglycemia, the level of TLR4 mRNA in myocardial tissue was significantly elevated, and signs of apoptosis were evident. Silencing TLR4 resulted in suppression of apoptotic cascades. According to Min, "This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene".

Patients receiving dialysis are at a heightened risk for sudden cardiac death

Sun, 14 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Approximately 500,000 Americans require dialysis to treat kidney disease; of that population nearly half of the deaths that occur are caused by cardiovascular disease. Dialysis patients are at elevated risk for sudden cardiac death, but physicians are unclear why these deaths occur because little research has been done to examine how to best manage heart disease in this high-risk population.

Northwestern Medicine cardiologist Rod Passman, MD, medical director for the Center for Atrial Fibrillation at the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital will present a paper at the American Heart Association's Scientific Sessions being held November 13 through 17 in Chicago about sudden cardiac death in dialysis patients. Passman is working to increase understanding within the medical community about this heightened mortality risk and how to prevent sudden cardiac death among this rapidly growing patient population.

Dialysis patients have extraordinarily high mortality rates with cardiac disease accounting for 43 percent of deaths in this population; data indicates that approximately 27 percent of the mortalities are due to sudden cardiac death, said Passman, who is also an associate professor of cardiology at Northwestern University's Feinberg School of Medicine. Patients on dialysis are excluded from clinical trials examining sudden cardiac death because of their kidney disease. The lack of research complicates clinicians' ability to understand the connection between renal disease and cardiovascular disease. The medical community needs to stop neglecting this community of patients because it is a rapidly growing group.

Sudden cardiac death is unexpected natural death from a cardiac cause within a short time period, generally less than an hour from the onset of symptoms in a person without prior condition that would appear fatal. In most cases, sudden cardiac death occurs because of ventricular arrhythmias (abnormal heart rhythms), including ventricular tachycardia (VT) or ventricular fibrillation (VF).

Risk of cardiac arrest in dialysis patients is related to age and dialysis duration, said Passman. A study by the United States Renal Disease Data System (USRDS) indicates longer dialysis duration is associated with higher mortality. This data also leads us to believe that end-stage renal disease is a primary promoter of cardiac disease and increased risk for sudden cardiac death.

By analyzing USRDS data, Passman and other researchers are beginning to better understand how cardiovascular disease affects renal patients and developing plans for preventing sudden cardiac death. The more understanding we gain in regards to why these patients are dying from sudden cardiac death, the better chance we have to save them, Passman explained. The best methods for prevention are medicinal options, including beta-adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin type II receptor blockers (ARB), or both external and implantable defibrillators.

Data also indicates a connection between potassium levels in a patient's dialysate prescription and sudden cardiac death. Patients who suffered a cardiac arrest during dialysis were twice as likely to be on low-potassium dialysate versus higher levels of potassium, which were associated with the best survival rates. According to Passman, clinicians should evaluate and modify dialysate prescription on an ongoing basis in an effort to minimize risk of sudden cardiac death.

By highlighting the issue of sudden cardiac death in dialysis patients, Passman hopes that he and other physicians will be able to better understand this unique patient population. There is very little research related to prevention of sudden cardiac death in dialysis patient; this group remains a mystery in terms of medical research, even though their numbers are growing, said Passman. The lack of research and study of cardiovascular disease in kidney patients is a problem that must be addressed. By understanding why dialysis patients are at such great risk for sudden cardiac death, we can begin to develop better standards for prevention.

JDRF clinical panel recommends next steps for artificial pancreas clinical testing

Wed, 10 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Diabetes experts at a meeting convened by the U.S. Food and Drug Administration (FDA) and the National Institutes of Health (NIH) took the next step in advancing efforts toward the development of an artificial pancreas: putting forth clinical recommendations to ensure the safe and effective testing of artificial pancreas technology in real-life situations. We are pleased at today's meeting there was a strong consensus among leading clinicians, researchers and industry leaders regarding the path toward outpatient studies for both low-glucose suspend and artificial pancreas systems.

Even with treatments available today, tight blood sugar control remains a challenge and daily struggle for those living with type 1 diabetes. In fact, the majority of people living with the disease are not achieving recommended target levels. An artificial pancreas, essentially a device that would both measure blood sugar and dispense appropriate amounts of insulin to keep levels in optimal range, would take much of the guesswork out of daily management of the disease, said Dr. Aaron Kowalski, Assistant Vice President of Treatment Therapies at JDRF. In the long-run, controlled blood sugar levels will help to lessen or avert the devastating complications from type 1 diabetes.

To date, artificial pancreas devices have been successfully tested in controlled inpatient or hospital settings, demonstrating the potential for this technology to improve blood sugar control. Now it must be tested safely in real-world conditions. And clear and reasonable regulatory guidelines must be established to ensure that the upcoming studies advance the technology to reach patients as soon as possible.

We believe a safe and effective first generation artificial pancreas system is possible with today's technology, even as we continue to encourage development of improved devices. Experts at today's FDA workshop outlined a clear path forward to safely speed the development and delivery of artificial pancreas systems to patients, said Jeffrey Brewer, President and CEO of JDRF.

To help advance these efforts, JDRF formed a Clinical Panel of internationally renowned leaders in the diabetes field to make recommendations to FDA on key clinical steps and issues critical to the advancement of studies of these systems outside of the hospital. Panel members speaking at today's workshop included David Nathan, Director, Clinical Research Center and Diabetes Center at Massachusetts General Hospital and Professor of Medicine, Harvard Medical School; and William Tamborlane, Professor and Chief of Pediatric Endocrinology and Diabetes, Yale University School of Medicine.

The panel developed a series of clinical recommendations that were shared at today's meeting. They were based on key areas addressed by the FDA, NIH, JDRF, clinicians and industry. First, the recommendations addressed questions on how should studies on artificial pancreas systems move safely from inpatient (hospital) settings to outpatient (real-world) testing. Second, the panel identified which subset of patients should be considered when testing artificial pancreas systems. The third area focused on how to ensure the safety of patients participating in the studies and eventually for everyday use. Lastly, the panel identified what outcomes should be measured in studies to demonstrate the safety and effectiveness of the device.

A summary of the panel's recommendations is available here. A full report by the panel will be forthcoming.

According to panel chair Robert Sherwin, M.D., Yale University, The panel believes, with certain safeguards, artificial pancreas systems can be safely tested in real world settings.

The incidence of type 1 diabetes is on the rise. Today's tools to manage the disease are insufficient. We have the technology at our disposal to make an artificial pancreas work. Now it's time to move forward quickly to define the regulatory pathway so final studies can be completed and better technologies can be made available to adults and children struggling with this difficult disease, added Mr. Brewer.

Exposure of humans to cosmetic UV filters is widespread

Tue, 02 Nov 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Amsterdam, 2 November, 2010 - An investigation conducted in the context of the Swiss National Research Programme (NRP50), Endocrine Disrupters: Relevance to Humans, Animals and Ecosystems, demonstrates for the first time that internal exposure of humans to cosmetic UV filters is widespread.

In the course of the Summer and Fall 2004, 2005 and 2006 (3 cohorts), human milk was sampled by mothers who had given birth at the University Women's Hospital in Basel. The participants filled out a detailed questionnaire with general questions and, as special feature, in depth questions on use of different types of cosmetic products.

Chemicals out of a large range of products including modern chemicals and classical persistent organic pollutants (POPs) were analyzed in the same human milk sample by analytical laboratories in Freiburg, Erlangen and Baden. The list comprised cosmetic UV filters, synthetic musk fragrances, pesticides, phthalates, parabens, flame retardants (polybrominated diphenylethers), and polychlorinated biphenyls (PCBs); in total 89 analyses per milk sample. The chemical analytical data of milk samples of individual mothers were then compared with the information obtained through the questionnaire.

The investigation revealed that one and the same human milk sample contained a large range of chemical contaminants, most of which are known to interact with endocrine systems. Individual exposure patterns differed between different types of chemicals. The study demonstrates for the first time that internal exposure of humans to cosmetic UV filters is widespread. Cosmetic UV filters were present in 85% of human milk samples, at concentrations comparable to PCBs. Synthetic musk fragrances were also present in the milk samples. The presence of UV filters in human milk was significantly correlated with the use of cosmetic products containing these UV filters. As a result, exposure patterns differed between individuals.

It seems plausible that exposure to other cosmetic constituents such as synthetic fragrances is also linked to the use of the corresponding products. However, this could not be investigated because musk fragrances are not declared. In contrast, classical contaminants such as PCBs, DDT and metabolites of DDT as well as some other persistent organochlor pesticides represented a rather uniform background exposure. Their levels were in part correlated with each other and also with fat-rich nutrition.

A total daily intake of each individual chemical was calculated for each individual infant from their individual levels in human milk. Calculation included fat content of individual milk samples, total daily milk intake per infant and body weight of the infant. Some infants exhibited values of daily intake of PCBs and several organochlor pesticides that were above US EPA reference dose values.

Margret Schlumpf and Walter Lichtensteiger, who lead the research said, Research on the effects of endocrine disrupters (chemicals interfering with hormone actions) has shown that it is of utmost importance to obtain information on simultaneous exposure of humans to different types of chemicals because endocrine active chemicals can act in concert. Information on exposure is particularly important for the developing organism at its most sensitive early life stages. Human milk was chosen because it provides direct information on exposure of the suckling infant and indirect information on exposure of the mother during pregnancy.

An important question during the research was: To what extent lifestyle can influence the presence of chemicals in breast milk? This question was the foundation for the preparation of the questionnaire. The questions were focused particularly on the use of cosmetic products; information on the relationship between the exposure of human populations to constituents of cosmetics and the presence of these constituents in the human body was limited and, in the case of UV filters, absent.

Gert-Jan Geraeds, Executive Publisher of

Gastric bypass alters sweet taste function

Tue, 02 Nov 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Gastric bypass surgery decreases the preference for sweet-tasting substances in obese rats, a study finding that could help in developing safer treatments for the morbidly obese, according to Penn State College of Medicine researchers.

Roux-en-Y gastric bypass surgery is the most common effective treatment for morbid obesity, said Andras Hajnal, M.D., Ph.D., associate professor, Department of Neural and Behavioral Science and Surgery. Many patients report altered taste preferences after having the procedure.

This surgery involves the creation of a small gastric pouch and bypassing a portion of the upper small intestine. Unlike other weight-reduction methods, it produces substantial and durable weight loss and significant improvements in obesity-related medical conditions including diabetes.

Study results in obese rats suggest that post-surgery changes in the gastrointestinal anatomy affect change in the brain that relate to taste.

Obese rats given gastric bypass surgery showed a reduced preference for high concentration sucrose water when compared to obese rats that did not have surgery. Researchers observed a similar decrease in preference with other sweet-tasting substances, but not for salty, sour or bitter substances. Researchers observed no change in preference in lean rats that had gastric bypass surgery.

The obese rats used do not have the ability to produce the receptor for feeling satiated shortly after a meal because they lack the gut hormone CCK-1. As a result, these rats consumed larger meals and, over time, became obese and developed type-2 diabetes. Interestingly, previous studies lead by the Penn State investigators found an increased sweet preference in these rats, which is also often seen in people struggling with weight management.

It appears that an uncontrolled appetite may get further boost from altered taste functions during development of obesity and diabetes, Hajnal said. How much of this vicious circle is due to changes in the neurons inside the brain, which receive taste sensations from the tongue and report to the higher order motivational brain centers, we don't know.

The researchers recorded the activity of 170 taste-responsive neurons in the brain. These showed a shift in the neurons' firing activity similar to the behavioral response, which was measured in lick rates of the rats within a ten-second time period. Neurons in the obese rats' brain responded more vigorously to higher-concentration sucrose water placed on the tongue when compared to lean rats. These effects were reversed by gastric bypass surgery and matched the response of lean rats -- a preference for lower concentration sucrose.

The rats that had gastric bypass surgery lost weight comparable to humans who received the surgery -- 26 to 30 percent of their weight -- and maintained the loss for a long period of time after surgery. Following surgery, the obese rats also showed a higher tolerance for glucose, indicating improvement in diabetes.

This supports the applicability of this rat model of Roux-en-Y gastric bypass to humans and also suggests that the observed taste changes following the surgery were not related to 'human factors' such as awareness and compliance to dietary and behavioral interventions, Hajnal said.

The researchers published their findings in the October issue of the

Liver hormone is a cause of insulin resistance

Tue, 02 Nov 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have identified a hormone produced and secreted by the liver as a previously unknown cause of insulin resistance. The findings, in the November issue of Cell Metabolism, a Cell Press publication, suggest a new target for the treatment of insulin resistance and type 2 diabetes, the researchers say.

The current study sheds light on a previously underexplored function of the liver; the liver participates in the pathogenesis of insulin resistance through hormone secretion, said Hirofumi Misu of Kanazawa University Graduate School of Medical Science in Japan.

The researchers had discovered earlier that genes encoding secretory proteins are abundantly expressed in the livers of people with type 2 diabetes. On the basis of those findings, Misu and colleagues began to suspect that, similar to the role of fat tissue, the liver might contribute to the development of type 2 diabetes and insulin resistance via secretory proteins they call hepatokines.

Now, the researchers report the results of comprehensive gene expression analyses, revealing that the liver expresses higher levels of the gene encoding selenoprotein P (SeP) in people with type 2 diabetes who are more insulin resistant. Blood levels of SeP are also increased in people with diabetes compared to healthy people.

Further studies in mice added support to the notion that the connection between SeP and insulin resistance is causal. When the researchers gave normal mice SeP, they became insulin resistant and their blood sugar levels rose. A treatment that blocked the activity of SeP in the livers of diabetic and obese mice improved their sensitivity to insulin and lowered blood sugar levels.

Misu said that SeP was known previously as a protein produced mainly in the liver, where it transports the essential trace element selenium from the liver to other parts of the body. But the protein's clinical significance and, more specifically, its role in glucose homeostasis weren't known.

In the development of insulin resistance, the researchers don't think SeP acts on its own. It is well known, they explain, that fat tissue is a main contributor to the development of insulin resistance by producing fat-derived hormones called adipokines. But they say they have preliminary evidence for a connection between SeP and adipokine production, which will be the subject of further investigation.

The new findings suggest that there may be other hormones derived from the liver with important and varied roles in the body, Misu and his colleague Toshinari Takamura add. Our study raises the possibility that the liver functions as an endocrine organ by producing a variety of hepatokines and that the dysregulation or impairment of hepatokine production might contribute to the development of various diseases.

Can Wii help control gestational diabetes?

Wed, 13 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) TORONTO, Ont., Oct. 13, 2010--Many women have trouble finding time to exercise in their busy lifestyles. That's especially true for pregnant women who live in northern climates such as Canada, where the weather can limit outdoor activity during winter months every year.

But exercise is critical to managing gestational diabetes, a growing problem that occurs in 2 to 9 per cent of pregnancies.

Researchers at St. Michael's Hospital have proposed a novel solution. They want to offer women recently diagnosed with gestational diabetes a Nintendo Wii gaming console, a Wii Fit activity platform and two activity-promoting games, Wii Sport and Wii Fit Plus. The goal is to see whether the women get more exercise and thereby lower their blood glucose levels and decrease the need for insulin.

We all know how hard it is to maintain a proper exercise regimen in the best of times. It is obviously much harder while pregnant. We thought that by combining a fun, home-based activity with a clinical goal we will be able to achieve an important health benefit for our patients with gestational diabetes, said Dr. Howard Berger, head of the high-risk pregnancy unit at St. Michael's.

Women usually have a blood test for gestational diabetes when they are 24 to 28 weeks pregnant. The treatment is diet and exercise, such as 20-30 minutes of walking a day. If that doesn't control their blood glucose levels, they have to take insulin, which happens in 15 to 66 per cent of women with gestational diabetes.

Women with gestational diabetes are at increased risk of developing diabetes and obesity later in life. They are also at increased risk of developing complications during pregnancy and delivery, including heavier babies, pre-eclampsia, premature births, higher rates of Cesareans and post-partum hemorrhage. Newborns of a diabetic mother may also suffer from metabolic complications including hypoglycemia (low blood glucose) and hyperinsulinemia, a condition also known as pre-diabetes.

Study participants will be patients at the hospital's diabetes in pregnancy clinic, part of the Women's Health Centre, which today moves back to 61 Queen St. E. following a $6.3 million renovation of their fourth- and fifth-floor offices and exam room and the building lobby.

Our new ambulatory center for women strives to treat women as a whole, offering the most appropriate care for their individual situation and incorporating the most recent advances in health care practice and technology, said Dr. Guylaine Lefebvre, chief of obstetrics and gynecology.

The renovations include bigger examining rooms, where the patient will remain while various health care professionals come to her, and bigger ultrasound rooms, with space for partners and relatives to be present. The architect for the project was from Diamond + Schmitt Architects, who also designed the hospital's new Li Ka Shing Knowledge Institute.

New discovery may help to identify the healthiest embryos in IVF treatment

Mon, 11 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Australian scientists have developed a potentially groundbreaking new measure of the health of an embryo and the likelihood of a successful pregnancy in IVF treatment.

The research could lead to significantly improved birth rates in IVF to help the one in six Australian couples experiencing infertility to achieve their dream of parenthood.

It also has the potential to predict the gender of an embryo prior to implantation.

The research by the University of Melbourne and Repromed was presented this week at the Fertility Society of Australia annual scientific meeting at the Adelaide Convention Centre.

Professor David Gardner, Head of the Department of Zoology at the University of Melbourne, said the study related specifically to the glucose intake of embryos from the solution in which they grow in the laboratory.

IVF units use this solution, or media as it is known, to provide a bed of nutrients for embryos fertilised in the laboratory from the eggs and sperm of couples who cannot naturally conceive. The glucose in embryo solution closely matches that which occurs naturally in the uterus.

Professor Gardner said fertility specialists knew the precise amount of glucose in the solution before inserting an embryo.

By measuring the level of glucose on day four or five after fertilisation, we can determine how much has been consumed by a growing embryo, he explained. There is clear cut evidence that the greater the glucose intake the healthier the embryo.

On average, IVF units generate between eight and ten embryos per cycle, of which about half will progress through cell division to what is known as the blastocyst stage after four to five days.

By measuring the glucose consumption of an embryo, we can better determine which is the healthiest embryo for transfer back to the patient.

The research involved 50 patients undergoing IVF. Thirty-two of the women had a positive pregnancy test after embryo transfer and 28 babies were born.

The 28 babies resulted from the embryos which had the highest glucose uptake, Professor Gardner said.

Previous studies with animals have shown that the healthiest blastocysts are those with the greatest glucose consumption indicating the likelihood of a successful pregnancy.

It is exciting to find that this process appears to be the same in people knowing that the glucose in embryo culture media is a major energy source for cell division and is required for biosynthesis to enable cell replication.

Professor Gardner said another potentially exciting aspect of the research was that female embryos appeared to take up more glucose than male embryos.

This is a very early observation, but it may have the potential to help identify gender at early embryo stage, he said.

Heart, kidney, diabetes and cancer MEP groups league against chronic disease to seek European commitment

Tue, 05 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) In an unprecedented effort to bring prevention of chronic diseases to the top of the EU agenda, the MEP Heart Group , the MEP Group for Kidney Health , the EU Diabetes Working Group and MEPs Against Cancer organise a joint meeting today in the European Parliament, together with representatives of health professionals and health activists at European level.

If we don't address these chronic diseases urgently, they threaten the Europe 2020 strategy, especially the goal to have 75% of the working population employed and productive says Linda McAvan, MEP and co-chair of the MEP Heart Group. Most of these chronic diseases are treatable but not curable, which explains why they generate an enormous financial burden due to treatment and care costs and loss of economic productivity.

Chronic diseases are largely preventable and in this respect the European Parliament has a major role to play says Frieda Brepoels, chair of the MEP Group for Kidney Health.

In a joint statement issued at the end of the meeting, MEPs call upon the competent authorities in the member states to urgently develop and improve policies aiming at tackling chronic diseases. A higher investment in prevention is needed, continues Frieda Brepoels, in particular by raising awareness about common risk factors and promoting healthy lifestyles.

Four major health determinants - tobacco, poor diet, alcohol and lack of physical activity - account for most chronic illness and death in Europe. Addressing chronic diseases will allow Europeans to live longer and healthier lives, stay longer in the workforce and contribute to reversing the alarming negative labour force growth which is predicted for 2020.

High tobacco and alcohol taxes, smoke free environment, good nutrition labelling which helps consumers make healthy choices and measures to prioritise the needs of pedestrians and cyclists over those of motorists in urban areas are but some of the few measures that politicians should put in place.

Alojz Peterle, Member of the European Parliament and President of MEPs Against Cancer (MAC), one of the co-organisers of the event said: 'We urge MEPs, the European Commission, the Council of Ministers and national governments to work together to tackle the problem of chronic diseases. It is only by working in partnership that we will be able to put in place effective Europe-wide policies aimed at preventing these conditions that cause so much suffering and death each year. Prevention is undoubtedly cheaper than disease management and treatment and, therefore, it makes economic sense to pursue these policies now at a time when many national governments are having to curb their expenditure.'

High death and disability rates due to fractures in Russia, Central Asia and Eastern Europe

Mon, 27 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Preliminary findings from an upcoming new report by the International Osteoporosis Foundation (IOF) show alarming projections and reveal the poor state of post-fracture care in the Russian Federation and many other countries in the region. The findings were announced today at a press conference in St. Petersburg at the IOF Summit of Eastern European and Central Asian Osteoporosis Patient Societies.

Osteoporosis, a disease of the bone which leaves people at increased risk of fracture, is most common in the older population. Population projections for most countries in the region predict that by 2050 there will be a decrease of the total population, but a significant increase (up to 56%) in the percentage of people aged 50 and over. As a result, in the Russia Federation alone the number of people with osteoporosis is expected to increase by a third by 2050.

Despite the major public health burden of osteoporosis-related fractures, the disease suffers from severe under recognition - mainly due to the lack of solid epidemiological and economic data which would help convince health authorities of the urgency of osteoporosis prevention. There are no formal hip or fragility fracture registries in most countries within the region and data on vertebral fractures, the most common osteoporotic fracture, are completely lacking. IOF President John Kanis stated, It is clear from the key findings that governments need to support wide scale epidemiological studies to collect data on the incidence of osteoporotic fractures.

DXA technology, diagnostic equipment which provides the most accurate method of diagnosis, is usually only accessible in main cities - yet in about one-third of the countries, more than 40% of the population lives in a rural area. In most countries, drug treatment for those at high risk of fracture is not, or is only partially, reimbursed - effectively making treatment unaffordable for the majority of citizens.

Low levels of calcium and vitamin D intake impact negatively on bone health. The average daily calcium intake in nearly all countries outlined in the report falls far below the FAO/WHO recommendations. In addition the majority of populations in the region suffer from severe vitamin D insufficiency. This not only affects fracture rates, but also causes rickets. In recent years the incidence of rickets (pediatric vitamin D deficiency) among Russian infants has ranged from 54% to 66% in some regions.

Although older people who sustain a hip fracture are at increased risk of death and suffer long term disability throughout the world, the report indicates that this problem is far more severe in the Russia Federation and in many other countries of the region. Professor Olga Lesnyak, Vice-President of the Russian Association on Osteoporosis and author of the report, called for action, There is an urgent need for health care providers to improve post hip fracture surgical care, she said. While in Western Europe most hip fracture patients receive operative treatment (the optimal standard of care), in the Russian Federation there is an extremely low rate of surgical treatment. Consequently there is high mortality rate after a hip fracture, reaching up to 45-52% during the first year after fracture in some Russian cities. Of the surviving hip fracture patients, 33% remain bed-ridden and 42% are capable of only very limited activities. Only 9% are able to return to the same level of daily activity as they had before their fracture.

IOF Chief Operating Officer Judy Stenmark stated, Wider and more equitable access to diagnostic tests and appropriate medication are required to stem the growing tide of fractures in the region.

Aerobic exercise relieves insomnia

Wed, 15 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO --- The millions of middle-aged and older adults who suffer from insomnia have a new drug-free prescription for a more restful night's sleep. Regular aerobic exercise improves the quality of sleep, mood and vitality, according to a small but significant new study from Northwestern Medicine.

The study is the first to examine the effect of aerobic exercise on middle-aged and older adults with a diagnosis of insomnia. About 50 percent of people in these age groups complain of chronic insomnia symptoms.

The aerobic exercise trial resulted in the most dramatic improvement in patients' reported quality of sleep, including sleep duration, compared to any other non-pharmacological intervention.

This is relevant to a huge portion of the population, said Phyllis Zee, M.D., director of the Sleep Disorders Center at Northwestern Medicine and senior author of a paper to be published in the October issue of Sleep Medicine. The lead author is Kathryn Reid, research assistant professor at Feinberg.

Insomnia increases with age, Zee said. Around middle age, sleep begins to change dramatically. It is essential that we identify behavioral ways to improve sleep. Now we have promising results showing aerobic exercise is a simple strategy to help people sleep better and feel more vigorous.

The drug-free strategy also is desirable, because it eliminates the potential of a sleeping medication interacting with other drugs a person may be taking, Reid said.

Sleep is an essential part of a healthy lifestyle, like nutrition and exercise, noted Zee, a professor of neurology, neurobiology, and physiology at Northwestern University Feinberg School of Medicine and a physician at Northwestern Memorial Hospital.

By improving a person's sleep, you can improve their physical and mental health, Zee said. Sleep is a barometer of health, like someone's temperature. It should be the fifth vital sign. If a person says he or she isn't sleeping well, we know they are more likely to be in poor health with problems managing their hypertension or diabetes.

The study included 23 sedentary adults, primarily women, 55 and older who had difficulty falling sleep and/or staying asleep and impaired daytime functioning. Women have the highest prevalence of insomnia. After a conditioning period, the aerobic physical activity group exercised for two 20-minute sessions four times per week or one 30-to-40-minute session four times per week, both for 16 weeks. Participants worked at 75 percent of their maximum heart rate on at least two activities including walking or using a stationary bicycle or treadmill.

Participants in the non-physical activity group participated in recreational or educational activities, such as a cooking class or a museum lecture, which met for about 45 minutes three to five times per week for 16 weeks.

Both groups received education about good sleep hygiene, which includes sleeping in a cool, dark and quiet room, going to bed the same time every night and not staying in bed too long, if you can't fall asleep.

Exercise improved the participants' self-reported sleep quality, elevating them from a diagnosis of poor sleeper to good sleeper. They also reported fewer depressive symptoms, more vitality and less daytime sleepiness.

Better sleep gave them pep, that magical ingredient that makes you want to get up and get out into the world to do things, Reid said.

The participants' scores on the Pittsburgh Sleep Quality Index dropped an average of 4.8 points. (A higher score indicates worse sleep.) In a prior study using t'ai chi as a sleep intervention, for example, participants' average scores dropped 1.8 points.

Exercise is good for metabolism, weight management and cardiovascular health and now it's good for sleep, Zee said.

Congressman to speak at meeting on diabetes and obesity

Tue, 14 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) U.S. Rep. Danny Davis (D-Chicago) will give opening remarks when the Institute of Medicine of the National Academies convenes a regional meeting Sept. 21 at the University of Illinois at Chicago to discuss the rapidly rising rates of diabetes and obesity in the U.S.

Obesity and diabetes are grave public health issues for our communities, particularly in underserved populations, Davis said. A recent report found that Illinois was one of eight states with childhood obesity rates greater than 20 percent. With 26.6 percent of our adults obese, Illinois ranked 26 among the nation's heaviest states. Addressing these issues through research, clinical care and community outreach is a top priority for academic institutions such as UIC and other area universities.

The UIC Midwest Conference on Diabetes and Obesity will bring together leading scientists, physicians and community health experts. Causes, treatment, preventive measures and policy issues will be discussed by participants from academia, industry and government. The conference, hosted by the IOM, UIC and the UIC College of Medicine, will be at the UIC Forum, 725. W. Roosevelt Road.

UIC is proud to co-sponsor this important meeting on a critical health concern, says UIC Chancellor Paula Allen-Meares, who is an elected member of the IOM and chairs a section of its membership committee. Diabetes has long been a research focus at UIC, where the Chicago Diabetes Project coordinates the research of collaborators on three continents to develop a cell-based therapy to achieve a functional cure. We look forward to the day when this scourge, along with its companion, obesity, is brought under control.

Diabetes is reaching epidemic proportions and may soon become the world's leading cause of death. According to the Chicago Diabetes Project, in 1985 there were 30 million diabetics; today the number has skyrocketed to more than 197 million. By 2025, diabetes is likely to affect more than 300 million people worldwide. The condition leads to serious medical complications including amputations, blindness, kidney failure, heart attacks and stroke. According to the Centers for Disease Control and Prevention, more than 80 percent of people with Type 2 diabetes, the most common form of the disease, are obese or overweight. The two conditions are so strongly associated that decades ago scientists began using the term diabesity.

The conference's morning session will focus on biomedical advances and prevention of risk. Following a lunch talk about the Chicago Diabetes Project, the afternoon session will address health policy and interventions. The keynote address, by Dr. Jerrold M. Olefsky of the University of California, San Diego, is on genetic and basic studies of the metabolic syndrome in animal models.

UC Davis receives $1 million NIH grant to improve health in No. Calif. Native American communities

Mon, 09 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) (SACRAMENTO, Calif.) -- UC Davis School of Medicine researchers will train Native American communities in Northern California to develop and implement culturally appropriate interventions to improve their health by decreasing obesity and type-2 diabetes, through a $1 million research grant from the National Institute of Diabetes and Kidney Diseases of the National Institutes of Health.

The communities include the Round Valley Indian Tribes of Covelo, Calif., Mendocino County, and communities served by Northern Valley Indian Health, Inc., which include Glenn County and portions of Butte, Tehama and Colusa counties.

This will be a unique situation in which university health researchers will collaborate with community members to teach them how to perform research on their own communities, to ensure that the research is culturally appropriate, acceptable and helpful, said Dennis Styne, study principal investigator and the Yocha Dehe Endowed Chair in Pediatric Endocrinology.

Community members will collect data about their community's health habits to, for example, learn what kinds of healthy foods and exercise resources are most helpful, and select and design the most effective interventions, Styne said.

Over one-third of all American Indian adults nationwide are obese, compared with about 22 percent of non-Hispanic whites. Among the Native American communities participating in the study, nearly 68 percent of adults are obese and 24 percent of children between 2 and 5 years old have body mass indexes in the 95th percentile for their ages.

Obesity is associated with type-2 diabetes, which can result in heart and kidney disease, nerve damage and blindness and lead to premature death. The condition has been described as a disease of disparity, disproportionately affecting low-income and ethnic minority populations. American Indians are 2.6 times as likely to be diagnosed with diabetes as non-Hispanic whites. Nationwide, the number of Native Americans diagnosed with diabetes doubled between 1991 and 2001. In the Round Valley and Northern Valley Native American communities, 11 percent are affected by type-2 diabetes.

The Native American community is disproportionately affected by diabetes and heart disease, hypertension, lipid problems and other diseases of disparity, Styne said. They are aware of the importance of the conditions and are committed to working to turn the tide.

Styne said that the two-year research initiative will train community members as research associates in the use of community-based and community-governed participatory research techniques, to ensure engagement in improving their health. The UC Davis researchers will work collaboratively with two established community-health centers that serve the Native American communities, the Round Valley Indian Health Center and Northern Valley Indian Health, Inc., with the full support of their boards of directors.

Partners at Round Valley will include Edward Whipple, outreach prevention coordinator at Round Valley Unified School District, fitness and health instructor at Mendocino Community College and an enrolled member of the Round Valley tribe; and Diann Simmons, a consultant with the Round Valley Sustainability Program. At Northern Valley Indian Health, UC Davis will partner with Vicki Shively, a nurse and member of the Choctaw Nation who has served for seven years as the center's community health director.

The study's co-investigators will be: Valarie Blue Bird Jernigan, training director of community-based participatory research for the project and a member of the Choctow Nation who is a senior research fellow at the University of Washington and a visiting assistant researcher at UC Davis; Diana Cassady, associate professor of public health sciences, who will collaborate on evaluation of the FitKid and FitTeen programs in Round Valley schools; and Karen Jetter, assistant research economist at the Agricultural Issues Center at UC Davis, who will direct training in socioeconomic survey methods.

Science leaders urge diabetes patients to talk with doctor before making changes to medication use

Thu, 15 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The Endocrine Society, American Diabetes Association and American Association of Clinical Endocrinologists issue joint statement in response to an FDA panel's recommendation to keep rosiglitazone (Avandia) on the market

The U.S. Food and Drug Administration's (FDA) Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee has completed their evaluation of the scientific research available on the safety of rosiglitazone. The deliberations of the panel reflected the complexity of the issues, with several members voting to add additional warnings or to withdraw the drug from the U.S. market. Ultimately, the final recommendation was to allow Avandia to remain on the market. Now that the expert panel has concluded its meeting, the FDA will review their recommendations and make the final decision on whether the drug remains available to patients.

Even with the panel's recommendation, the amount of scrutiny the drug has received may lead some diabetes patients who currently take rosiglitazone to want to stop taking the drug. The Endocrine Society, American Diabetes Association and the American Association of Clinical Endocrinologists urge patients to not make any changes to their medication use without discussing their treatment with their physician.

Patients should continue taking all currently prescribed medications unless instructed otherwise by their health care provider, said Dr. Robert A. Vigersky, immediate Past President of The Endocrine Society. Stopping diabetes medications can cause significant harm and result in higher levels of blood glucose that may cause severe short term health problems and could increase the risk of diabetes-related complications in the long term.

The worst outcome would be to not treat diabetes properly, thereby risking its complications, said Dr. Daniel Einhorn, President of the American Association of Clinical Endocrinologists. This unintended consequence has happened with past inquiries into diabetes medications, and we very much want to avoid it happening again.

Reports regarding the cardiovascular safety of rosiglitazone have not been definitive. While some analyses have suggested an increased cardiovascular risk with use of the diabetes drug others have not shown substantial evidence of such an association.

Patients should be aware that regardless of the opinion and decisions on rosiglitazone, there are numerous drugs available to maintain glucose control in people with type 2 diabetes. Patients should discuss these options with their health care providers, said Dr. Richard Bergenstal, President, Medicine and Science, American Diabetes Association.

Following any decision from the FDA, The Endocrine Society, The American Diabetes Association and the American Association of Clinical Endocrinologists will provide detailed information interpreting FDA action for both health care professionals and patients with diabetes.

USC wins $56.8M NIH award for clinical and translational research

Thu, 15 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The University of Southern California (USC) has received a prestigious $56.8 million Clinical and Translational Science Award from the National Institutes of Health (NIH) to support and promote scientific discoveries and their application in real-life settings to health and health care. The CTSA will have an important focus on health issues of people living in densely populated urban environments.

The award, which will be distributed over the next five years, was given to the USC-based Los Angeles Basin Clinical and Translational Science Institute (CTSI). CTSI was established in 2006 to connect basic scientists to clinical and community researchers and practitioners with a goal of accelerating the translation of laboratory discoveries into practice. Principal investigator is Thomas A. Buchanan, M.D., director of the Los Angeles Basin CTSI, and associate dean for clinical research at the Keck School of Medicine of USC.

We congratulate principal investigator Dr. Tom Buchanan and the highly interdisciplinary USC team for winning this award, said Carmen A. Puliafito, M.D., M.B.A., dean of the Keck School of Medicine. An extraordinarily strong grant application resulted in USC receiving the first Clinical and Translational Science Award in Los Angeles. The application received a score of 12 on a scale of 10 to 90 (10 is a perfect score).

Faculty from eight USC schools and Childrens Hospital Los Angeles will partner with Kaiser Permanente Southern California, the Los Angeles County departments of Health Services and Mental Health, the Community Clinic Association of Los Angeles County, and more than 30 community health organizations in greater Los Angeles to address the specific needs of the urban and diverse patient populations found in USC's backyard of downtown Los Angeles.

We positioned our CTSI as not only an institute focused on health research, but also as a partnership among some of the largest providers of health care in Los Angeles. We are working collaboratively with others on campus and off campus, using L.A. as a real world laboratory to address issues that are important to the community here, Buchanan said.

With this award, USC joins a consortium of 55 health research centers in 28 states and the District of Columbia that are developing new ways to advance medical research in many disease areas and conditions, including cancer, mental illness, neurological disorders, cardiovascular disease, diabetes and obesity.

The selected research institutions work together as a national consortium to improve the way biomedical research is conducted across the country. The consortium, funded through the Clinical and Translational Science Awards (CTSA), shares a common vision to reduce the time it takes for laboratory discoveries to become treatments for patients, and to engage communities in clinical research efforts. It also is fulfilling the critical need to train a new generation of clinical researchers. The CTSA program is led by the National Center for Research Resources, part of National Institutes of Health.

USC competed for the award against 38 other institutions, including three major academic institutions in Southern California. Nine institutions received grant awards this year, and the NIH has stated that it plans to implement a maximum of 60 Clinical and Translational Science Awards overall.

While USC's Los Angeles Basin CTSI has already been successful at launching community research and interdisciplinary projects on a small scale, large-scale funding from the new NIH award will open the doors to development of a premier clinical and translational institute with the potential for a very large impact on health research and health care.

The Los Angeles Basin CTSI has four main goals for the CTSA. The first is to create an integrated academic environment that promotes and supports clinical and translational research. The second is to develop new interdisciplinary teams and projects to address top research priorities and health issues of people living in urban environments. The third is to train a new generation of investigators for clinical and translational science. The fourth goal is to share research findings locally, through the CTSI partnership, and nationally, through the consortium of institutions with CTSAs, to foster better health.

The CTSI has secured participation of eight schools at USC, including Medicine, Cinematic Arts, Dentistry, Education, Engineering, Law, Pharmacy and Social Work.

Some interdisciplinary projects are currently under way. For example, leveraging talent from health sciences, engineering, cinema and informatics, faculty members recently developed an interactive computer game that helps autistic children better interact on an emotional level, one of the deficits of those with the disorder.

Higher testosterone may raise risk of heart disease in elderly men

Thu, 01 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A large U.S. multicenter study shows that older men with higher testosterone levels are more likely to have a heart attack or other cardiovascular disease in the future. The results were presented at The Endocrine Society's 92nd Annual Meeting in San Diego.

The study finding contradicts smaller studies that have shown that testosterone levels are not associated with higher rates of cardiovascular disease, said presenting author Kristen Sueoka, MD, a resident physician at the University of California, San Francisco.

Many in the general public are using testosterone supplements for various medical problems, including low sex drive and mood disorders, which are not life-threatening. These men may unknowingly be placing themselves at higher risk for cardiovascular disease, she said.

Study participants were age 65 or older and included 697 community-dwelling men who were participating in the National Institutes of Health-funded study, Osteoporotic Fractures in Men (MrOS). None of these men were receiving testosterone therapy, according to the study abstract.

All subjects had blood tests to determine their testosterone levels. The investigators then divided the men into quartiles, or four groups, of testosterone range to observe trends in rates of coronary heart disease events. This type of heart disease results from plaque-clogged or narrowed coronary arteries, also called atherosclerosis. A coronary heart disease event included a heart attack; unstable angina, which is chest pain usually due to atherosclerosis and which doctors consider a prelude to a heart attack; or an angioplasty or bypass surgery to clear blocked arteries.

During an average follow-up of nearly 4 years, 100 men, or about 14 percent, had a coronary disease event, in particular, heart attacks, Sueoka said. After the researchers adjusted for other potential contributing risk factors for heart disease, such as elevated cholesterol, they found that higher total testosterone level relates to an increased risk of coronary disease. Men whose total testosterone was in the highest quartile (greater than or equal to 495 nanograms per deciliter, or ng/dL) had more than twofold the risk of coronary disease compared with men in the lowest quartile (below 308 ng/dL).

Other important measures of testosterone in the body and of a protein that tightly binds with testosterone (sex hormone-binding globulin) also showed a close relationship between testosterone and coronary heart disease, Sueoka said.

The investigators did not divide the men by normal or abnormal testosterone levels because the definition of abnormal levels depends on many factors, including increasing age. In fact, says Sueoka, Men with the highest testosterone could potentially be at risk for heart disease regardless of the definition of normal levels.

One day testosterone measurements may be used to help predict which men are more likely to develop cardiovascular disease, she said. But we need more studies to confirm that high testosterone is a risk factor for heart disease.

Study finds why some women are sub-fertile with a poor response to ovarian stimulating hormones

Tue, 29 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Rome, Italy: Researchers have discovered that some women carry a genetic variation that makes them sub-fertile and less likely to respond to ovarian stimulating hormones during fertility treatment. The discovery opens the way to identifying these women and devising personalised fertility treatments that could bypass the problem caused by the genetic abnormality.

Dr Maria Lalioti told the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome today (Tuesday) that she and her colleagues from the Yale University Medical School, New Haven (USA), had found that some women had an abnormal hormone receptor on cells surrounding oocytes (eggs). This abnormal receptor impaired the function of normal receptors that were also present and resulted in the affected women responding less well to Follicle Stimulating Hormone (FSH), which is given to women during fertility treatment to stimulate the production of more than one oocyte.

Dr Lalioti, as assistant professor in the Department of Obstetrics Gynecology and Reproductive Sciences at Yale, said: When a woman undergoes in vitro fertilisation, she receives medication called Follicle Stimulating Hormone to produce more than one oocyte, which is the normal production each month. Cells called granulosa cells, which surround the oocyte, receive the FSH; these cells excrete other factors that 'feed' the oocyte. The granulosa cells have proteins present on their surface called FSH receptors (or FSHR) and it is these proteins that stick to the FSH and then carry signals into the cell's interior. When we looked at a portion of these granulosa cells in the laboratory we saw that in some women, who produced very few oocytes, there were some receptors that lacked a piece of the protein, although there were still other, normal FSHR in the women's cells.

The abnormal FSHR contained a deleted sequence of protein called exon 2 that is an important part of the protein that binds the FSH; FSHR with the exon 2 deletion was only detected in women younger than 35 who had a poor response to FSH and yielded less than four oocytes in a follicle stimulating cycle.

We produced the normal and abnormal protein in the lab in a different type of cell called HEK293 (Human Embryonic Kidney) which is a common cell type used in the labs to examine properties of proteins. We saw that when the abnormal receptor was present, the normal one could no longer work as well as it does when it is the only protein present, explained Dr Lalioti. The receptor is normally present on the cell surface in order to meet and bind FSH, and it needs to go through a number of cellular checkpoints inside the cell that assure the quality of the protein presented on the surface. We saw that the abnormal receptor remains longer in one of these checkpoint compartments, indicating that the cell has detected a problem and is trying to correct it. In this way the abnormal FSHR can contribute to an abnormally low response to stimulation in certain women undergoing IVF.

Dr Lalioti's discovery of the mechanism behind why some young women have a poor response to FSH has important implications for future research and treatment of these women. The importance of this finding is that it creates a link between genetic variation and sub-fertility. These women have a normal menstrual cycle and they may present to the fertility centre as patients with unexplained infertility, before their first IVF cycle that would reveal an ovarian stimulation defect, she said.

Our finding explains why these women have a lower response to FSH. Currently, FSH is the only medication used to stimulate ovarian response, but once other medications are available that can bypass the receptor for FSH, they can be tested on these women. Also, at present we cannot predict if the women would profit from having higher doses of medication, and, in fact, some preliminary data from other groups show the opposite: that lower FSH may be more beneficial.

Future research will examine the FSHR signalling mechanisms within the cell and investigate how newly developed drugs might bypass the problems created by the genetic abnormality. In the future, this could lead to personalised treatments for a sub-group of patients, said Dr Lalioti.

It is not known how many women have this particular genetic variation. Dr Lalioti found it in two out of five women that she tested. These patients are hard to recruit because most patients with a low response to FSH do not complete the IVF cycle for financial reasons, she said. We need to recruit more patients to discover how common it is. She and her colleagues will need a year to recruit and test more women, to set up collaborations with more fertility centres and to start to test new drugs that could promote oocyte production more effectively in these women.

Study finds no link between diabetes drug rosiglitazone and increased rate of heart attack

Tue, 29 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The diabetes drug rosiglitazone has been under intense scrutiny since a 2007 study in the New England Journal of Medicine looked at more than 40 clinical trials and linked the drug's use with increased risk of heart attack and death from heart disease.

Now, in a post-trial analysis of results from an international clinical trial of 2,368 diabetes patients with cardiovascular disease, researchers at Washington University School of Medicine in St. Louis and several major centers across the country report no increased rate of heart attack or death in patients taking rosiglitazone. In fact, this analysis found a lower combined rate of death, heart attack and stroke associated with patients taking rosiglitazone compared with those who were not taking a thiazolidinedione drug (rosiglitazone or pioglitazone).

Richard G. Bach, MD, a Washington University researcher and medical director of the Cardiac Intensive Care Unit at Barnes-Jewish Hospital, presented this research June 29 in a late-breaking clinical studies session at the American Diabetes Association's Scientific Sessions in Orlando, Fla.

These new results are relevant in the debate over rosiglitazone's cardiovascular safety, according to Bach. In an advisory panel scheduled to meet next month, the U.S. Food and Drug Administration (FDA) will reassess the safety of rosiglitazone and determine whether it should remain on the market.

As a result of the questions raised by the meta-analysis in the New England Journal and certain other studies, some have cautioned that rosiglitazone should not be used in patients with coronary heart disease and diabetes, says Bach, also associate professor of medicine in the Cardiovascular Division at the School of Medicine. Our data carefully examine use of rosiglitazone in a large cohort of patients with established coronary artery disease and suggest that treatment with rosiglitazone was not associated with an increased risk of ischemic cardiovascular events, like heart attack and stroke, and in a number of analyses it was associated with a lower rate of those events, he says.

Rosiglitazone, made by GlaxoSmithKline under the brand name Avandia, is an insulin-sensitizing drug. In type 2 diabetes, the pancreas continues to make insulin, but the body's tissues can't use it well. Rosiglitazone and other thiazolidinediones (TZDs) do not provide more insulin but reduce insulin-resistance, helping the body regulate blood sugar with the insulin it already makes.

Rosiglitazone was one of several drugs used to control blood sugar in the BARI 2D clinical trial (Bypass Angioplasty Revascularization Investigation 2 Diabetes). Between 2001-08, BARI 2D was a multi-center trial directed by the University of Pittsburgh that investigated treatment strategies for patients with both type 2 diabetes and cardiovascular disease. The trial was designed to determine the best strategies for treating patients with both conditions.

To address their cardiovascular disease, patients in BARI 2D were randomly assigned to receive either intensive medical therapy plus revascularization treatment (such as angioplasty or bypass surgery) or intensive medical therapy alone (with the possibility of revascularization treatment later if their symptoms did not improve).

To address their diabetes, the same patients were randomly assigned to receive either insulin-providing drugs (such as insulin itself) or insulin-sensitizing drugs (such as rosiglitazone or another drug, metformin). As a result, a large number of patients were treated with rosiglitazone during approximately five years of follow up in the trial. This aspect of BARI 2D provided a way to investigate rosiglitazone's cardiovascular safety after it came under scrutiny in 2007. In addition, Bach notes the importance of this new analysis because it looks at a population of patients already at high risk of cardiovascular events like heart attack and stroke.

Compared with patients not receiving a TZD, those who did take rosiglitazone showed a 28 percent lower combined rate of death, heart attack and stroke. In addition, the rate of stroke on its own was 64 percent lower in patients receiving rosiglitazone. Both of these differences were statistically significant. Rates of heart attack and death on their own showed no significant difference between those who took rosiglitazone and those who did not. In line with other studies, rosiglitazone was associated with increased risk of bone fracture, especially in women.

While these results support rosiglitazone's safety in patients with existing heart disease, Bach points out a weakness in the new analysis. Because BARI 2D was designed to assess treatment strategies, not the safety of rosiglitazone, the drug was not randomly assigned. It was the treating physician who decided whether to prescribe rosiglitazone to a particular patient, in line with the study protocol.

Agent Orange exposure linked to Graves' disease in Vietnam veterans, UB study finds

Mon, 28 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- Vietnam War-era veterans exposed to Agent Orange appear to have significantly more Graves' disease, a thyroid disorder, than veterans with no exposure, a new study by endocrinologists at the University at Buffalo has shown.

Ajay Varanasi, MD, an endocrinology fellow in the UB Department of Medicine and first author on the study, garnered first prize in the oral presentation category for this research at the American Association of Clinical Endocrinologists annual meeting held in Boston in April.

Our findings show that Vietnam veterans who came in contact with Agent Orange are more likely to develop Graves' disease than those who avoided exposure, says Varanasi.

The autoimmune disorder was three times more prevalent among veterans who encountered the dioxin-containing chemical. We also looked at other thyroid diagnoses, but we didn't find any significant differences in thyroid cancer or nodules.

Agent Orange is a defoliant that was used in Vietnam to destroy crops and reduce jungle foliage that could shelter enemy combatants. The herbicide contains dioxin, which has chemical properties similar to the thyroid hormones.

Graves' disease is an autoimmune disease associated with overactivity of the thyroid gland. This gland releases the hormones thyroxine (T4) and triiodothyronine (T3), which control body metabolism and are critical for regulating mood, weight, and mental and physical energy levels.

Varanasi and colleagues assessed the prevalence of major thyroid diagnoses in the Veterans Administration electronic medical record database for upstate New York veterans born between 1925 and 1953, the age group that would have been eligible for military service during the Vietnam era. They conducted the research at the Buffalo VA Medical Center.

They compared the frequency of diagnoses of thyroid cancer, nodules, hypothyroidism and Graves' disease in veterans who identified themselves as being exposed to Agent Orange (23,939) or not exposed to Agent Orange (200,109).

Analyzing data on thyroid conditions, we found no difference in the prevalence of thyroid nodules or cancers between the exposed and non-exposed groups, says Varanasi. Graves' disease, however, was three times more prevalent in the exposed group.

Interestingly, hypothyroidism [lower than normal thyroid] was less common in the exposed group.

Varanasi says that in view of the known effects of dioxin on the immune system, further research should be conducted on the increased prevalence of Graves' disease in Vietnam veterans. His research group is planning to continue this investigation either in vitro or in animal models.

Lifestyle intervention reduces preschoolers' body fat, improves fitness

Tue, 22 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Migrant children are at increased risk of obesity, but a new study shows that a program teaching multiple lifestyle changes to predominantly migrant preschoolers and their parents helps the children reduce body fat and improve fitness. The results will be presented Monday at The Endocrine Society's 92nd Annual Meeting in San Diego.

Such interventions may be needed to help curb the global obesity epidemic, the study's lead author Jardena Puder, MD, said. A senior resident at the University of Lausanne, Lausanne, Switzerland, Puder said, Even young children have high rates of obesity today.

In the United States, about 14 percent of children ages 2 to 5 years are obese, statistics show.

The public health program in this study attempted to reduce the risk of obesity among preschool children from areas of Switzerland with high migrant populations. Specifically, it encouraged the children to increase their physical activity, improve nutrition, get more sleep and reduce audiovisual media use, especially TV watching. Excessive media use can contribute to lack of physical activity, and insufficient sleep in early life may play a role in childhood obesity, according to the authors.

Puder and her colleagues included children, their parents and their preschool teachers in the program, which took place during the 2008-2009 school year. They randomly selected 40 preschool classes in migrant-populated areas and then randomly assigned 20 of the classes to participate in the program and 20 classes to not participate and thus serve as controls. Of the 655 children enrolled in the study, 73 percent had at least one migrant parent.

The program included information materials for teachers and parents as well as two informational and discussion evenings for parents. Children received structured lessons from the regular teachers about physical activity, nutrition, media use and sleep.

In addition, the school environment was adapted, such as by adding a climbing wall. This gave unstructured movement an automatic place within school, Puder said.

Before and after completion of the program, the researchers evaluated numerous measures, including overall fitness on an obstacle course and aerobic fitness. For the latter, children performed the 20-meter shuttle run test, in which they repeatedly ran at increasing speeds between two lines spaced 20 meters (just over 22 yards) apart.

Compared with the control group, the group of children who participated in the program had significantly improved overall and aerobic fitness, according to the abstract. Additionally, the intervention group had greater reductions in total and percent of body fat, waist size and media use. They also improved more than controls in some aspects of nutritional behavior, Puder said.

Besides Health Promotion Switzerland, the Swiss National Science Foundation helped fund this study, called Ballabeina. This word means seesaw in Rhaeto-Romanic, a Latin language spoken in parts of Switzerland. Puder said, The name stands for a life in motion but also in balance.

Early-life exposure to BPA may affect testis function in adulthood

Mon, 21 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Exposure to environmental levels of the industrial chemical bisphenol A, or BPA, in the womb and early life may cause long-lasting harm to testicular function, according to a new study conducted in animals. The results are being presented Monday at The Endocrine Society's 92nd Annual Meeting in San Diego.

We are seeing changes in the testis function of rats after exposure to BPA levels that are lower than what the Food and Drug Administration and Environmental Protection Agency consider safe exposure levels for humans, said Benson Akingbemi, PhD, the study's lead author and an associate professor at Auburn (Ala.) University. This is concerning because large segments of the population, including pregnant and nursing mothers, are exposed to this chemical.

Many hard plastic bottles and canned food liners contain BPA, as do some dental sealants. BPA acts in a similar manner as the female sex hormone estrogen and has been linked to female infertility. This chemical is present in placenta and is able to pass from a mother into her breast milk. In their study of the male, Akingbemi and colleagues saw harmful effects of BPA at the cellular level, specifically in Leydig cells. These cells in the testis secrete testosterone, the main sex hormone that supports male fertility. After birth, Leydig cells gradually acquire the capacity for testosterone secretion, Akingbemi explained.

The process of testosterone secretion was decreased in male offspring of female rats that received BPA during pregnancy and while nursing. The mothers were fed BPA in olive oil at a dose of either 2.5 or 25 micrograms of BPA per kilogram of body weight. Akingbemi said this is below the daily upper limit of safe exposure for humans, which federal guidelines currently put at 50 micrograms per kilogram of body weight. A control group of pregnant rats received olive oil without BPA. Male offspring, after weaning at 21 days of age, received no further exposure to BPA.

Using a combination of analytical methods, the investigators studied the development of Leydig cells in male offspring. The capacity for testosterone secretion was assessed at 21, 35 and 90 days of age. The amount of testosterone secreted per Leydig cell was found to be much lower in male offspring after early-life exposure to BPA than in offspring from control unexposed animals.

Although BPA exposure stopped at 21 days of age, BPA's effects on Leydig cells, which were seen immediately at the end of exposure and at 35 days, remained apparent until 90 days of age, when the rats reached adulthood, Akingbemi said. Therefore, the early life period is a sensitive window of exposure to BPA and exposure at this time may affect testis function into adulthood.

Demonstrated in vivo the transfer of maternal thyroid hormones to the fetus

Mon, 12 Apr 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Until now there were only indirect evidence of the transfer of thyroid hormones from mother to fetus through the placenta during pregnancy. That event is very important because the maternal thyroid hormones appear to play a key role in the development of the nervous system and other organs of the fetus; so it's true that in case of maternal thyroid disease, such hypothyroidism, have a direct bearing on the unborn child with reduction, also significant, to its Q.I.. That passage of maternal thyroid hormones to the fetus was clarified through a study, based on a transgenic mouse model, designed and built by a team of Italian researchers led by Prof. Alfredo Pontecorvi, Endocrinologist at Catholic University in Rome.

Thyroid hormones play a role in the development of the nervous system. The lack of these hormones at birth, if not promptly diagnosed and treated, causes severe and irreversible brain damage, producing irreversible mental deficit known as cretinism. In fact, it does not develop adequately the dense network of interconnections between nerve cells (neurons) and single nerve fibers are not properly covered with insulating myelin sheath covering, which is similar to the rubber sheath that insulates electrical wires, that allows fast transfer of nerve impulses from one neuron to another. It is as if an electrical system had not activated all the necessary contacts and electrical wires were exposed, resulting in a serious malfunction of the entire plant.

Thyroid hormones appear to be important even during the embryo-fetal period, in the first trimester of pregnancy, when fetal thyroid function has not yet activated - explains Pontecorvi -. It is at this time, in fact, that neurons, forming the heritage breed brain of each of us (about 100 billion neurons), migrate in their homes outright and differentiate to form different centers and brain structures. From this time the nerve cells not will reproduce more while, from 20 years onward, will be lost by each of us at a rate of about 100.000 per day. It is therefore fundamental that the right amount of maternal thyroid hormones is assured during the embryo-fetal development of our neuronal kit.

During the first trimester of pregnancy it is estimated that are maternal thyroid hormones to ensure the fetal thyroid hormone needs, thereby affecting the neuronal development.

It is known that children of mother with hypothyroidism during pregnancy show a significantly lower QI than the children of mothers with a normal thyroid function - continues Pontecorvi. A similar reduction in QI has been observed in the case of pregnant mothers with a low level of thyroxine, although not exactly hypothyroid, a condition that tends to occur particularly in situation of iodine deficiency. But all these are only indirect evidences in favor of the passage through the placenta of maternal thyroid hormones to the fetus.

What so far was only assumed or inferred has been demonstrated by a recent study, all designed and manufactured in Italy, published in the prestigious

Rapid-acting insulin in inhaled form

Tue, 23 Mar 2010 10:40:52 PST

( from http://www.rxpgnews.com ) Scientists today described a new ultra-rapid acting mealtime insulin (AFREZZA™) that is orally inhaled for absorption via the lung. Because the insulin is absorbed so rapidly, AFREZZA's profile closely mimics the normal early insulin response seen in healthy individuals. AFREZZA is awaiting approval by the U. S. Food and Drug Administration (FDA). This presentation took place at the 239th American Chemical Society National Meeting, being held here this week.

Andrea Leone-Bay, Ph.D. and colleagues at MannKind Corporation said that the new insulin product, uses the Technosphere® technology, a delivery technology that is applicable to a wide variety of other drugs that are currently injected. Like insulin, these medications are proteins that would be digested and destroyed in the stomach if taken by mouth.

One such product, MKC-180, is a Technosphere® formulation of a natural hormone that controls appetite and is under investigation as a therapy for obesity using pulmonary delivery. "In nonclinical studies remarkable reductions in food intake have been observed," Leone-Bay said. MannKind is also evaluating Technosphere® technology with drugs that treat pain and osteoporosis.

"Our proprietary Technosphere® Technology platform is based on particles formed by the self-assembly of a small molecule," Leone-Bay explained. "Drugs can be loaded onto these particles, which are then dried to form a dry powder. Using a thumb-sized device, patients inhale a small amount of the powder, roughly equivalent to a pinch of salt. This powder dissolves immediately after inhalation and the drug is absorbed into the patient's bloodstream. Most importantly, the drug is absorbed ultra-rapidly so it becomes effective much more quickly than an injection of the same drug. For some drugs, ultra-rapid systemic delivery provides distinct clinical advantages over injection, including profiles that match the body's natural responses in processes like hormone secretion."

AFREZZA™ (insulin human rDNA origin) Inhalation Powder is an ultra-rapid acting insulin intended for use at mealtime to control the rapid rise in blood sugar levels that occurs in people with diabetes immediately after a meal. At other times, people with diabetes would take injections of other kinds of insulin.

Leone-Bay said AFREZZA™ controls glucose as well as current state-of-the-art treatments, poses a lower risk of hypoglycemia than that typically associated with mealtime insulin therapy, and leads to less weight gain compared to other insulin treatments," according to Leone-Bay. "Additionally, and importantly, AFREZZA™ provides the unique benefit of a small, discreet, and easier-to-use inhalation device."

Frequent napping associated with an increased prevalence of type 2 diabetes

Mon, 01 Mar 2010 13:24:48 PST

( from http://www.rxpgnews.com ) A study in the March 1 issue of the journal Sleep shows that frequent napping is associated with an elevated prevalence of type 2 diabetes and impaired fasting glucose in an older Chinese population.

Results show that the prevalence of type 2 diabetes was 36 percent higher (adjusted odds ratio = 1.36) in participants who reported napping four to six times a week and 28 percent higher (OR = 1.28) in those who napped daily. Similar associations were found between napping and impaired fasting glucose. The observed associations were unaltered in statistical analyses that removed participants with potential ill health and daytime sleepiness, suggesting it is less likely that diabetes leads to daytime sleepiness and raising the possibility that napping may increase the risk of diabetes.

According to the authors, napping in China is a social norm, which is practiced by all ages primarily as a habit started in childhood. In Western countries, napping is less common and is often unplanned and prompted by sleepiness likely caused by aging, deteriorating health status or nighttime complaints.

Lead author Neil Thomas, PhD, reader in epidemiology at the University of Birmingham, U.K., said that additional research is needed to determine if napping itself plays a causative role in the development of type 2 diabetes, or if other factors are involved.

"In many non-Mediterranean, Western countries a large proportion of those that nap are generally older or have other conditions that cause tiredness and create an urge to nap," said Thomas. "The napping can therefore be a marker of disease."

This cross-sectional study analyzed baseline data from the Guangzhou Biobank Cohort Study, a collaboration between the Guangzhou Number 12 People's Hospital and the Universities of Birmingham and Hong Kong. The community-based study took place in Guangzhou, China, where 19,567 participants between the ages of 50 and 93 years were recruited from 2003 to 2004 and 2005 to 2006. The sample comprised 13,972 women with a mean age of 61.4 years and 5,595 men with an average age of 64.2 years.

Participants underwent a half-day assessment, which included a structured interview on lifestyle and medical history, and a physical examination. Self-reported frequency of napping was obtained by questionnaire, and type 2 diabetes was assessed by a fasting blood glucose sample and/or self-reports of physician diagnosis or treatment. Participants were asked to describe their napping habits and daytime sleepiness.

Type 2 diabetes was identified in 13.5 percent of the sample and was more prevalent in people who reported napping daily (15.1 percent) and in those who napped four to six times per week (14.7 percent). Logistic regression models were constructed to assess the relationship between napping and diabetes and impaired fasting glucose, adjusting for demographics, lifestyle, sleep habits, health status, body fat and metabolic markers.

At least one nap per week was reported by 67.2 percent of participants, more commonly in males (76.4 percent) than in females (63.6 percent). About 59.4 percent of these people reported napping daily. Total sleep duration was longer and daytime sleepiness was reported less often in more frequent nappers than in people who never napped.

In a sub-sample of 3,822 participants who were re-contacted for additional information about sleep habits, there was a statistically significant trend of increasing risk of diabetes with longer nap duration. Compared with people who never took naps, the risk of diabetes was 41 percent higher (OR = 1.41) for people who took naps that lasted longer than 30 minutes and 35 percent higher (OR = 1.35) for people whose naps lasted 30 minutes or less.

The authors noted that the association between napping and diabetes was observed despite the fact that nappers had higher levels of physical activity, which has been shown to reduce the risk of diabetes. This suggests that the relationship between napping and diabetes might have been stronger had it not been offset by the protective effects of physical activity. The authors added that there will be profound public health implications in China if the relationship between napping and increased risk of type 2 diabetes is confirmed in longitudinal studies, as the nation is currently affected by an emerging diabetes epidemic.

Changes during menopause increases risk of heart disease and stroke

Tue, 23 Feb 2010 05:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO- When women hear the word menopause, they often think about hot flashes, hormone shifts and mood swings. But what about heart disease? Studies show a woman's risk of heart disease intensifies drastically around the time of natural menopause, which for most women is around the age of 50. This news may come as a surprise, but experts explain that understanding risk factors is an important first step, and reassure women that there are ways to lower your risk.

Many women younger than 50 have not yet gone through menopause and still have high levels of the female hormone estrogen in their blood, which is thought to help protect the heart. After menopause, however, the levels of estrogen in a woman's body drop significantly and can contribute to the higher risks of cardiovascular disease, explains Vera Rigolin,MD, associate director of the Center for Women's Cardiovascular Health in the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital.

Weight gain is also a factor that may play a role in postmenopausal risk of heart disease. Maintaining a healthy weight often becomes difficult after your body experiences a change in hormone levels. Extra mass can take a toll on the body causing physical inactivity, high blood pressure, diabetes, and high cholesterol, all risk factors that can lead to heart attack and stroke.

Detecting heart disease in women can be difficult. Many women are unaware that symptoms of the disease may differ from those of men. Although women often experience chest discomfort when presenting with a heart attack, they commonly have other, more subtle symptoms, including fatigue, nausea, shortness of breath, jaw pain and general discomfort in the chest and abdominal area.

In some women, plaque can build in the smallest blood vessels called the microvascular circulation. These blockages do not show up in an angiogram, says Rigolin. In these cases, we often use Magnetic Resonance Imaging (MRI) with medication to visualize blood flow within the small blood vessels when other standard tests do not provide us answers.

Women, especially those who are menopausal can reduce the risk of heart disease by adopting a healthy lifestyle.

If you are a smoker, quit immediately and avoid second hand smoke. Eat a diet rich in fruits and vegetables and exercise at least three times per week to maintain a healthy body weight, says Rigolin.

Rigolin also recommends visiting your health care provider at least once per year to have your blood pressure, blood sugar and cholesterol levels checked.

Stress hormone, depression trigger obesity in girls

Tue, 23 Feb 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Depression raises stress hormone levels in adolescent boys and girls but may lead to obesity only in girls, according to researchers. Early treatment of depression could help reduce stress and control obesity -- a major health issue.

This is the first time cortisol reactivity has been identified as a mediator between depressed mood and obesity in girls, said Elizabeth J. Susman, the Jean Phillips Shibley professor of biobehavioral health at Penn State. We really haven't seen this connection in kids before, but it tells us that there are biological risk factors that are similar for obesity and depression.

Cortisol, a hormone, regulates various metabolic functions in the body and is released as a reaction to stress. Researchers have long known that depression and cortisol are related to obesity, but they had not figured out the exact biological mechanism.

Although it is not clear why high cortisol reactions translate into obesity only for girls, scientists believe it may be due to physiological and behavioral differences -- estrogen release and stress eating in girls -- in the way the two genders cope with anxiety.

The implications are to start treating depression early because we know that depression, cortisol and obesity are related in adults, said Susman.

If depression were to be treated earlier, she noted, it could help reduce the level of cortisol, and thereby help reduce obesity.

We know stress is a critical factor in many mental and physical health problems, said Susman. We are putting together the biology of stress, emotions and a clinical disorder to better understand a major public health problem.

Susman and her colleagues Lorah D. Dorn, professor of pediatrics, Cincinnati Children's Hospital Medical Center, and Samantha Dockray, postdoctoral fellow, University College London, used a child behavior checklist to assess 111 boys and girls ages 8 to 13 for symptoms of depression. Next they measured the children's obesity and the level of cortisol in their saliva before and after various stress tests.

We had the children tell a story, make up a story, and do a mental arithmetic test, said Susman. The children were also told that judges would evaluate the test results with those of other children.

Statistical analyses of the data suggest that depression is associated with spikes in cortisol levels for boys and girls after the stress tests, but higher cortisol reactions to stress are associated with obesity only in girls. The team reported its findings in a recent issue of the

First-generation artificial pancreas system used overnight can improve diabetes control

Sat, 06 Feb 2010 12:48:53 PST

( from http://www.rxpgnews.com ) In a landmark study in children and teenagers with type 1 diabetes, JDRF-funded researchers at the University of Cambridge showed that using a first-generation artificial pancreas system overnight can lower the risk of low blood sugar emergencies while sleeping, and at the same time improve diabetes control.

Results from the studies are published in the February 5, 2010 issue of The Lancet, available online at www.thelancet.com.

The trials tested the safety and effectiveness of a first-generation artificial pancreas system used overnight in a hospital setting with participants between 5 and 18 years of age with type 1 diabetes. The system combined commercially available blood glucose sensors and insulin pumps, controlled by a sophisticated computer program that determined insulin dosage based on blood glucose levels while the participants slept.

Maintaining recommended blood sugar levels overnight is a major issue for people with type 1 diabetes - and particularly for the families of children with diabetes - because of the possibility of blood glucose dropping dangerously low during sleep and going unnoticed, which can lead to seizures, coma, and in some cases be fatal.

Notably, the Cambridge study showed that the children and teenagers spent twice as much time during the night within targeted blood glucose levels when their diabetes was regulated with the artificial pancreas system than when they followed conventional "manual" therapy. And low blood sugars were minimized.

"These studies show that automated systems not only can help people manage diabetes by maintaining good control, they will also improve quality of life for the people with type 1 diabetes and their families by lowering the risk for hypoglycemia," said Roman Hovorka, Ph.D., from the Institute of Metabolic Science at the University of Cambridge, the principal investigator of the study and lead author of the paper. "These results suggest that closed-loop devices may be able to significantly lower the patient's risk of developing complications later in life by reducing or even overcoming the burden of hypoglycemia."

"Without a doubt, the biggest worry for parents of kids with type 1 diabetes is that their child will have a low blood sugar emergency during the night, when they're hard to identify," said Aaron Kowalski, Ph.D., Assistant Vice President of Metabolic Control at JDRF and Director of the JDRF Artificial Pancreas Project. "This study is proof of principle that diabetes in kids can be safely managed overnight with an artificial pancreas. We need to redouble our efforts to move the artificial pancreas from a concept in the clinic to a reality in the home of kids and adults with type 1."

The first phase of the Cambridge study compared the effectiveness of a simple artificial pancreas system used overnight with standard blood testing and insulin delivery using a pump. It showed that the time participants spent in target blood glucose levels (between 70 mg/dL and 140 mg/dL) improved from 39% to 52%. The second phase of the study evaluated the effects of a using the same artificial pancreas system overnight with the additional variable of the participants eating a particularly large meal, which can impact overnight blood glucose levels. The results were comparable to the first phase of the research. The third phase of the study evaluated the effects of moderately intense exercise, which can also impact blood sugar levels. Using the automated system in this setting showed the greatest improvement in blood sugar control, with the amount of time spent in the target range increasing from 48% to 78%.

"The pooled data from the closed loop studies showed that blood glucose levels were 61% in target, and even increased to 75% in target after midnight when closed-loop became fully effective," said Dr. Hovorka. "Based on these results, this study is a significant step towards an artificial pancreas."

The Cambridge studies were randomized, controlled trials involving 17 children and adolescents conducted at the Wellcome Trust Clinical Research Facility at Addenbrooke's Hospital in Cambridge, United Kingdom over the course of 54 nights. Twelve subjects were used for the first study; 6 subjects were used for the second, and 9 for the third. Some 33 nights were on a closed-loop artificial pancreas system, while 21 nights were controlled (on standard therapy). During the closed-loop studies, continuous glucose measurements were fed into a computer program every 15 minutes, which calculated the insulin infusion rate; the insulin pump was adjusted manually by a research nurse. During control nights, the subject's standard insulin pump settings were applied.

Type 1 diabetes is an autoimmune disease in which the immune system attacks and kills off the cells in the pancreas that produce insulin, a hormone that enables people to convert food into energy. It affects 3 million American children, adolescents, and adults.

To manage their disease, people with type 1 diabetes need to measure their blood sugar multiple times throughout the day (typically by pricking a finger for a drop of blood), and pump insulin or inject themselves multiple times daily to keep blood sugar levels within a healthy range. That daily routine continues for life, because insulin administration does not cure diabetes.

Research has shown that good blood sugar control is a key factor in reducing the risk of the devastating long-term complications of the disease, such as blindness and kidney disease - but that the fear of low blood sugar emergencies often prevents many people from achieving tight control, and remains a constant concern for those who manage their diabetes well. The landmark Diabetes Control and Complications Trial (DCCT) showed that with intensive insulin therapy, excellent blood glucose control was obtained, but at the expense of a considerable increase in hypoglycemia.

About JDRF's Artificial Pancreas Project
This study is the latest development within JDRF's Artificial Pancreas Project, and stems from the progress made since 2006 in the JDRF-funded Artificial Pancreas Consortium, a group of university-based mathematicians, engineers, and diabetes experts that has developed the computer programs needed for an artificial pancreas, and established their scientific feasibility. These academic studies within the Artificial Pancreas Project are an excellent complement, and essential to JDRF's work with industry participants to develop first -generation systems.

JDRF announced the first major non-exclusive industry initiatives of the Artificial Pancreas Project last month, when it entered into a non-exclusive partnership with Animas, a Johnson & Johnson company, to develop a first-generation artificial pancreas system. JDRF also announced a non-exclusive partnership with BD (Becton, Dickinson and Company) aimed at developing novel insulin delivery products - a key component of developing safe and effective artificial pancreas systems.

The eventual, ultimate goal of the JDRF Artificial Pancreas Project is speeding the development of automated diabetes management systems. The goal of an artificial pancreas has also been embraced by the U.S. Food and Drug Administration, which along with JDRF and National Institutes of Health, brought together scientists, regulators, industry, and patients for scientific workshops n the subject in 2005 and 2008; the FDA has designated an artificial pancreas as one of its "critical path" initiatives.

An artificial pancreas would measure blood sugar through a continuous glucose monitor (CGM), which continuously reads the glucose levels through a hair-thin tube inserted just below the skin, typically on the stomach. The CGM would beam those readings to an insulin pump. In an advanced system, the pump would house a sophisticated computer program that would automatically calculate the necessary amount of insulin, based on the CGM's glucose readings, and deliver the right amount of insulin.

The development of an artificial pancreas system is an essential step towards an ultimate cure for type 1 diabetes - a "bridge to a cure."

Study confirms that calcium and vitamin D together help prevent fractures

Fri, 15 Jan 2010 09:22:51 PST

( from http://www.rxpgnews.com ) Taking both calcium and vitamin D supplements on a daily basis reduces the risk of bone fractures, regardless of whether a person is young or old, male or female, or has had fractures in the past, a large study of nearly 70,000 patients from throughout the United States and Europe has found.

The study included data published in 2006 from clinical trials conducted at UC Davis in Sacramento as part of the Women’s Health Initiative (WHI). It appears online in this week’s edition of the British Medical Journal.

“What is important about this very large study is that goes a long way toward resolving conflicting evidence about the role of vitamin D, either alone or in combination with calcium, in reducing fractures,” said John Robbins, professor of internal medicine at UC Davis and a co-author of the journal article. “Our WHI research in Sacramento included more than 1,000 healthy, postmenopausal women and concluded that taking calcium and vitamin D together helped them preserve bone health and prevent fractures. This latest analysis, because it incorporates so many more people, really confirms our earlier conclusions.”

Led by researchers at Copenhagen University in Denmark, Robbins and an international team of colleagues analyzed the results of seven large clinical trials from around the world to assess the effectiveness of vitamin D alone or with calcium in reducing fractures among people averaging 70 years or older. The researchers could not identify any significant effects for people who only take vitamin D supplements.

Among the clinical trial results analyzed was Robbins’ WHI research, which was part of a 15-year, national program to address the most common causes of death, disability and poor quality of life in postmenopausal women such as cardiovascular disease, cancer and osteoporosis. Those trials were primarily designed to study the effect of calcium and vitamin D supplementation in preventing hip fractures, with a secondary objective of testing the supplements on spine and other types of fractures, as well as on colorectal cancer. The results were published in the Feb. 16, 2006 edition of the New England Journal of Medicine.

Fractures are a major cause of disability, loss of independence and death for older people. The injuries are often the result of osteoporosis, or porous bone, a disease characterized by low bone mass and bone fragility. The National Osteoporosis Foundation estimates that about 10 million Americans have osteoporosis; 80 percent of them are women. Four of 10 women over age 50 will experience a fracture of the hip, spine or wrist in their lifetime, and osteoporosis-related fractures were responsible for an estimated $19 billion in health-related costs in 2005.

“This study supports a growing consensus that combined calcium and vitamin D is more effective than vitamin D alone in reducing a variety of fractures,” said Robbins. “Interestingly, this combination of supplements benefits both women and men of all ages, which is not something we fully expected to find. We now need to investigate the best dosage, duration and optimal way for people to take it.”

UCSF diabetes, brain tumor stem cell grants to drive development of therapies

Thu, 29 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Two teams of UCSF scientists have received grants from the California Institute for Regenerative Medicine to advance their stem cell based strategies for treating diabetes and brain tumors. The intent of the grants is for teams to file new drug applications to the U.S. Food and Drug Administration within four years, driving potential therapies toward clinical trials.

The two grants, awarded to collaborative scientific teams, total $39.2 million.

The diabetes grant is co-led by investigator Jeffrey Bluestone, PhD, director of the UCSF Diabetes Center, in collaboration with Novocell, Inc. Other UCSF members of the team are Michael German, MD, PhD; Matthias Hebrok, PhD; and Qizhi Tang, PhD.

The brain tumor grant is led by Mitchel Berger, MD, chair of the UCSF Department of Neurosurgery, in collaboration with Ludwig Institute for Cancer Research and Burnham Institute for Medical Research. Other UCSF members of the team are C. David James, PhD; Tomoko Ozawa, MD, PhD; Russell Pieper, PhD; Mei-Yin Polley, PhD; Michael Prados, MD; and Elizabeth Read, MD.

The projects are among 14 disease team grants announced today (Oct. 28, 2009) by CIRM. The grants focus on conditions ranging from brain tumors and diabetes to HIV, heart damage and amyotrophic lateral sclerosis, among others. They are the first issued by CIRM with the explicit intent of driving the development of therapies for approval by FDA for testing in clinical trials.

The multidisciplinary collaborations are intended to hasten the clinical trial development process, avoiding mistakes sometimes discovered late in the game and ensuring that clinically relevant issues are considered early.

The diabetes team, lauded as a dream team by the CIRM working group reviewers, received $19,999,937 over four years. The goal is to encapsulate islet progenitor cells generated from human embryonic stem cells in a durable, retrievable device and implant them into patients. The cells, which differentiate into glucose responsive islet beta cells after transplantation in vivo, have proven to be a successful strategy in treating rodents with chemically-induced diabetes.

The critical early proof-of-concept milestones have been completed, says Bluestone. Now we need to perform the manufacturing and laboratory testing required to assure reliable production of a safe and effective product, thereby generating the data needed to seek Food and Drug Administration approval to test the therapy in humans.

This is a very exciting early pre-clinical step, but, as is always the case in science, there are likely to be unexpected hurdles as we move forward, he says.

If successful, a Phase 1 safety trial in Type 1 diabetic patients could begin in three-four years from the initiation of the project.

The brain tumor team, which received $19,162,435, was characterized by the CIRM leaders as pioneers and leaders in their respective fields. The team will refine their strategy of using adult and fetal neural stem cells, as well as mesenchymal stem cells, genetically engineered to contain a tumor-killing gene to home in on glioblastoma multiforme, the most common and aggressive form of brain tumor. The studies in rodents engineered to develop human brain tumors were successful.

The strategy is based on the team's discovery that neural stem cells naturally seek out brain tumor cells and other types of disease cells. If successful, this approach would be an important advance in treating brain tumors of all kinds, says Berger. Current approaches -- surgery, radiation, pharmacological drugs and gene therapies -- are unable to reach widely disseminated tumor cells that become dispersed within normal brain structures.

If the strategy is approved by the FDA, it would be tested first in patients with recurring glioblastoma multiforme.

NIEHS awards Recovery Act funds to address bisphenol A research gaps

Wed, 28 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) For Immediate ReleaseWednesday, October 28, 2009

Contact:Robin Mackar, NIEHS(919) 541-0073

NIEHS Awards Recovery Act Funds to Address Bisph

Researchers studying the health effects of the chemical bisphenol A (BPA) gathered in North Carolina to launch an integrated research initiative to produce data that will allow for a comprehensive assessment of its possible human health effects.

Researchers who just received funds from the American Recovery and Reinvestment Act to study BPA were brought together to meet with scientists from academia and government already working on the compound. The meeting was held Oct. 6, 2009 at the National Institute of Environmental Health Sciences (NIEHS).

The meeting is part of an effort to support human and animal research that will help determine if current exposures to BPA in the general population pose a potential health risk. NIEHS is part of the National Institutes of Health (NIH) and has the lead in supporting research to study the potential effects that chemicals, such as BPA, may have on human health. President Obama allocated $5 billion in Recovery Act funds to the NIH, with about $14 million going to NIEHS for research on BPA.

We know that many people are concerned about bisphenol A and we want to support the best science we can to provide the answers, said Linda Birnbaum, Ph.D., who serves as director of the NIEHS and the National Toxicology Program (NTP), an interagency program for the U.S. Department of Health and Human Services. Bringing the key BPA researchers together at the onset of new funding will maximize the impact of our expanded research effort.

NIEHS will invest approximately $30 million over two years on BPA-related research. This includes existing grants, the newly awarded Recovery Act grants and supplements, in-house research and NTP projects. The NTP effort is part of a larger five-year commitment to collaborate with the U.S. Food and Drug Administration's National Center for Toxicological Research to examine long-term health outcomes resulting from developmental exposures.

BPA is a chemical used primarily in the production of polycarbonate plastics and epoxy resins. People, including children, are exposed to BPA in food and beverages when it leaches from the internal epoxy resin coatings of canned foods and also from consumer products such as polycarbonate tableware, food storage containers, water bottles and baby bottles. In 2008, NTP and NIEHS concluded that there is evidence from animal studies that BPA may be causing adverse effects. But researchers are uncertain about whether the changes seen in the animal studies would result in human health problems. For this reason, NIEHS identified BPA as a priority area.

The innovative two-year grants provided through the Recovery Act will support human and animal studies that address many of the research gaps identified by expert scientific panels, and provide a better understanding of how this chemical may impact human health.

We want the new grantees to be able to hit the ground running, said Jerry Heindel, health scientist administrator at the NIEHS who oversees much of the institute's portfolio on BPA. Having the key players talking to one another as they begin new research efforts will stimulate collaboration, create opportunities to share resources, and encourage researchers to develop reliable and reproducible methods that will allow for a comprehensive assessment of the human health effects of BPA.

In animal studies, there is some evidence linking BPA exposure with infertility, weight gain, behavioral changes, early onset puberty, prostate and mammary gland cancer and diabetes. For the newly funded research, two-year animal and human studies will focus on either developmental exposure or adult chronic exposures to low doses of BPA. Researchers will be looking at a number of health effects including behavior, obesity, diabetes, reproductive disorders, development of prostate, breast and uterine cancer, asthma, cardiovascular diseases and transgenerational or epigenetic effects. The 10 Recovery Act NIH Grand Opportunities grants focusing on BPA research have been awarded to:

Obesity expert named Life Scientist of the Year

Wed, 28 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) A Monash University physiologist, whose research into weight management, obesity and diabetes has led to significant medical breakthroughs and drug design, has been awarded one of the nation's top research honours.

Michael Cowley received the prestigious Commonwealth Science Minister's Prize for Life Scientist of the Year.

Professor Cowley was last night presented with the award by the Minister for Innovation, Industry, Science and Industry Senator Kim Carr at Parliament House in Canberra.

The prize is granted to an internationally-renowned scientist who has completed their PhD within the last 10 years, and whose research has the potential to advance human welfare or society. He received $50,000, a silver medallion and a lapel pin.

I am tremendously grateful to receive this award, Professor Cowley said.

It's wonderful to know that my team and I are being recognised for the therapies we are developing for obesity.

Professor Cowley from the Department of Physiology has shown that neural circuits in the brain sense blood glucose and fat levels in the body. However a broken internal regulator can impair appetite regulation and lead to obesity, increasing the risk of Type 2 diabetes.

Professor Cowley has gone on to develop a combination anti-obesity drug called Contrave that can reactivate the fat sensor in obese patients and help them lose weight. In a large clinical trial in the US, participants who took Contrave lost between five and 10 per cent of their body weight in one year, with minimal to moderate side effects. Contrave combines new formulations of two existing drugs: Bupropion, an antidepressant; and Naltrexone, an addiction medication.

If the Food and Drug Administration approves the drug for prescription use in the US, Contrave could, subject to regulatory approval, be licensed in Australia.

Senior Deputy Vice-Chancellor and Deputy Vice-Chancellor (Research) Professor Edwina Cornish, who nominated Professor Cowley for the prize, said she was delighted with his success.

Michael's discoveries have the potential to radically change how we treat metabolic disease, and help Australia deal with a recognised crisis in Indigenous and non-Indigenous health, Professor Cornish said.

Professor Cowley's award caps off a successful year. He has received a Pfizer Australia Senior Research fellowship, Austin Doyle Lectureship, and Victorian Endowment for Science, Knowledge and Innovation Fellowship. Professor Cowley is also the inventor of 85 patents; co-founder and former Chief Scientific Officer of US-based biotechnology company, Orexigen Therapeutics; and has published 40 papers in peer-reviewed journals. His research has been profiled in the national and international media.

UGA geneticist receives $2 million federal stimulus grant for research on the thymus

Thu, 17 Sep 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The National Institutes of Health have awarded, as part of the American Reinvestment and Recovery Act, a two-year, $2 million grant to a University of Georgia genetics researcher and her colleagues for studies on the thymus, the organ in humans that produces disease-fighting T-cells.

Nancy Manley, a professor of genetics and chair of UGA's Interdepartmental Biology Group, is the principal investigator on the grant, which will support studies on molecular mechanisms regulating thymic epithelial cells during aging. The new grant supports a collaborative program between UGA, the University of Texas M. D. Anderson Cancer Research Center in Science Park, Tex., and the Center for Stem Cell Research at the University of Edinburgh in Scotland.

Other principal investigators are Ellen Richie, professor of carcinogenesis (Texas) and Clare Blackburn, group leader (Edinburgh).

This research is an excellent example of how the stimulus money is providing jobs in science and, at the same time, helping unravel new findings that could be important for human health, said Manley.

The grant will allow Manley to hire two research scientists, a laboratory technician and a full-time administrator.

While research on the thymus may seem arcane, it is, in fact, the subject of intense interest and extends and expands work in which Manley has been involved for some years now.

Last year, Manley's lab, using the mouse as a biological model, provided the first evidence that a key gene may be crucial to maintaining the production of the thymus and its disease-fighting T-cells after an animal's birth.

The discovery could help scientists find out how to turn the thymus back on so it could produce T-cells long after it normally shuts down most of its function, which, for humans, occurs by early adulthood. If the finding leads to further ways to manipulate the gene, the result could be a new avenue for the body to fight disease more effectively as it ages.

Such things as infectious diseases, inflammation and heart problems are all related to immune response, Manley said last year. You don't have to think far to see how understanding the effect of this gene could affect the quality of life for older people and others as well.

The newly funded research will try to discover the actual mechanisms by which the thymus shuts down and how these changes affect immune system function during aging. If and when that mechanism is found, scientists may find a way to turn the organ's function back on permanently or at specific times in the life of a human or an animal to fight disease or aging. An ultimate payoff might be longer and healthier lives for people.

The thymus is an organ located in the upper part of the human chest cavity, behind the sternum. This organ is the location where important systemic infection fighters called T-cells develop. Over the past two decades, T-cell counts have become part of everyday dialogue due to their importance in monitoring HIV/AIDS and other disorders.

The thymus slowly begins to shut down early in life and becomes largely inactive by early adulthood. Still, that's fine for most people, since an entire lifetime supply of T-cells is produced in that time. But, for some people, the loss of irreplaceable T-cells through disease can lead to chronic illnesses and a shortened life.

Until recently, scientists had thought that the thymus after birth was unable to regenerate T-cells because no known regulatory mechanism existed that might allow doctors to turn back on the thymus if a person's T-cells were compromised. There are now, however, some treatments currently in trials that can transiently rejuvenate the thymus and increase thymic output in humans.

The problem has been, though, that the mechanisms by which all this works are poorly understood, and all current treatments have systemic effects that can cause unacceptable side effects in all but the most seriously ill, who are more willing to tolerate them in exchange for possible benefit.

So far, the possibility of this working looks very good, said Manley.

While the mouse model doesn't precisely mimic human response, it is close enough so that biologists and geneticists can often draw conclusions from mouse trials on how humans will respond.

Though the ability of science to manipulate this gene and potentially the production of T-cells isn't going to happen next week, it may not be that far down the road, either. Under best circumstances, the researchers should know within five to 10 years whether the therapeutic ability to turn back on the production of T-cells is possible.

ERC Starting Grant for the researcher of kidney diseases

Fri, 11 Sep 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The European Research Council (ERC) expects to fund some 240 top researchers in its second prestigious ERC Starting Grant competition. This new wave of grantees follows the 299 researchers who received grants in the first Starting Grant competition in 2007.

In total, 2503 proposals were submitted to the second Starting Grant call.

Sanna Lehtonen's research group is studying the kidney glomerular ultrafiltration in both health and under pathological conditions, concentrating especially on studying the development of albuminuria that is an indicator of kidney disease. Specifically, we are interested in the pathophysiological mechanisms leading to the development of diabetic nephropathy, a serious complication of diabetes, Lehtonen says.

Up to one third of diabetic patients develop nephropathy. Microalbuminuria is the earliest sign of the complication, which may ultimately develop into end-stage renal disease requiring dialysis or a kidney transplant. Insulin resistance has been associated with an increased risk for diabetic nephropathy. Interestingly, glomerular epithelial cells or podocytes have recently been found to be insulin responsive and to increase their glucose uptake upon insulin stimulation. It has also been shown that intact filamentous actin cytoskeleton is required for the insulin response. Our studies concentrate on analyzing the role of insulin signaling and glucose transport and the regulation of actin cytoskeleton in podocytes thereby aiming to define the mechanisms leading to perturbations in the kidney ultrafiltration function and development of albuminuria, Lehtonen tells.

The aim of Lehtonen's ERC project called DiaDrug is to clarify the mechanisms leading to the development of insulin resistance in podocytes and to study the association between insulin resistance and the development of albuminuria. The researchers will develop transgenic zebrafish and mouse models to study the role of proteins associated with insulin signaling in podocytes, both under normal and pathologic conditions.

Further, we aim to identify novel drug leads to treat insulin resistance by performing high-throughput small molecule library screens on the developed transgenic fish models. The ultimate goal is to find a treatment to combat the early stages of nephropathy in diabetic patients, Lehtonen says.

Sanna Lehtonen started her studies on kidney already during the early 1990's as a PhD student. Her thesis project was on developmental biology, and in particular, about identifying and characterizing novel genes associated with epithelial cell differentiation in the kidney. Later her studies have turned more in the direction of kidney diseases and most recently concentrated on analyzing the development of albuminuria during the development of diabetic nephropathy.

Diabetes is increasing at an alarming rate worldwide. Renal complication is the most serious of its complications and is also associated with an increased risk of cardiovascular disease. Treating diabetes consumes a large bulk of the healthcare costs in all countries, and therefore understanding the mechanisms leading to the development of the complications, especially nephropathy, identifying it at an earlier stage and finding novel drug targets and drugs to prevent the progression of the complication are currently under intensive research, Lehtonen states.

Receiving the ERC grant was really fantastic news for me. Now we can finally do some things that we were earlier able to only think and dream about, Lehtonen says.

DNA mutations linked to diabetes

Thu, 03 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Genes that regulate the energy consumption of cells have a different structure and expression in type II diabetics than they do in healthy people, according to a new study from the Swedish medical university Karolinska Institutet published in Cell Metabolism. The researchers believe that these 'epigenetic mutations' might have a key part to play in the development of the disease.

Type II diabetes is characterised by a lower sensitivity to insulin in muscles and organs, and a reduced ability to consume energy in the form of glucose. Heredity and environmental factors (e.g. exercise) are both involved in the disease pathogenesis, but scientists are still unclear as to the mechanisms behind it.

A research group at Karolinska Institutet has now shown that genes in the muscle cells of diabetics are chemically modified through what is known as DNA methylation. They found that in muscles cells taken from patients with early-onset diabetes, a gene designated as PGC-1α was modified and had reduced expression. PGC-1α controls other genes that regulate the metabolism of glucose by the cell.

The team has also demonstrated that DNA methylation occurs rapidly, when cells from healthy people are exposed to certain factors associated with diabetes, such as raised levels of free fatty acids and cytokines. DNA methylation is a form of epigenetic regulation, a process involving chemical modifications that are imposed externally on genes and that alter their activity without any change to the underlying DNA sequence.

"This type of epigenetic modification might be the link that explains how environmental factors have a long-term influence on the development of type II diabetes," says Juleen Zierath, who led the study. "It remains to be seen whether the DNA methylation of this gene can be affected by, say, dietary factors."

Fat in the liver -- not the belly -- is a better marker for disease risk

Mon, 24 Aug 2009 04:00:00 PST

( from http://www.rxpgnews.com ) New findings from nutrition researchers at Washington University School of Medicine in St. Louis suggest that it's not whether body fat is stored in the belly that affects metabolic risk factors for diabetes, high blood triglycerides and cardiovascular disease, but whether it collects in the liver.

Having too much liver fat is known as nonalcoholic fatty liver disease. The researchers report online in the journal PNAS Early Edition that when fat collects in the liver, people experience serious metabolic problems such as insulin resistance, which affects the body's ability to metabolize sugar. They also have increases in production of fat particles in the liver that are secreted into the bloodstream and increase the level of triglycerides.

For years, scientists have noted that where individuals carried body fat influences their metabolic and cardiovascular risk. Increased fat inside the belly, known as visceral fat, is associated with an increased risk of diabetes and heart disease.

Data from a large number of studies shows that visceral fat is associated with metabolic risk, which has led to the belief that visceral fat might even cause metabolic dysfunction, says senior investigator Samuel Klein, M.D. However, visceral fat tracks closely with liver fat. We have found that excess fat in the liver, not visceral fat, is a key marker of metabolic dysfunction. Visceral fat might simply be an innocent bystander that is associated with liver fat.

Klein, the Danforth Professor of Medicine and Nutritional Science, directs the Division of Geriatrics and Nutritional Science and the Center for Applied Research Studies, as well as Washington University's Center for Human Nutrition. He says most of our body fat, called subcutaneous fat, is located under our skin, but about 10 percent is present inside the belly, while much smaller amounts are found inside organs such as the liver and muscle.

This study compared obese people with elevated and normal amounts of liver fat. All subjects were matched by age, sex, body mass index, percent body fat and degree of obesity. Through careful evaluations of obese people with different amounts of visceral fat or liver fat, Klein's team determined that excess fat inside the liver identifies those individuals who are at risk for metabolic problems.

We don't know exactly why some fats, particularly triglycerides, will accumulate inside the liver and muscle in some people but not in others, says first author Elisa Fabbrini, M.D., Ph.D., assistant professor of medicine. But our data suggest that a protein called CD36, which controls the transport of fatty acids from the bloodstream into different tissues, is involved.

Fatty acids are the building blocks for making fats, known as triglycerides. Klein, Fabbrini and their colleagues found that CD36 levels were lower in fat tissue and higher in muscle tissue among people with elevated liver fat.

Fabbrini and Klein say changes in CD36 activity could be responsible for diverting circulating fatty acids away from fat tissue and into liver and muscle tissue, where they are converted to triglyceride. Increased tissue uptake of fatty acids could be responsible for metabolic dysfunction.

Klein says those who are obese but don't have high levels of fat in the liver should be encouraged to lose weight, but those with elevated liver fat are at particularly high risk for heart disease and diabetes. He says they need to be treated aggressively to help them lose weight because dropping pounds can make a big difference.

Fatty liver disease is completely reversible, he says. If you lose a small amount of weight, you can markedly reduce the fat content in your liver. In fact, even two days of calorie restriction can cause a large reduction in liver fat and improvement in liver insulin sensitivity.

Scarring key to link between obesity and diabetes

Thu, 13 Aug 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The team, in collaboration with University Hospital Aintree, the University of Warwick and researchers in Sweden, found that people classified as obese and those with pre-diabetes have raised levels of a protein called SPARC, that can cause tissue scarring. The research revealed that an increase in insulin, a hormone that controls blood sugar levels, and leptin, a hormone that regulates appetite, can trigger an increase in SPARC, which can prevent the proper storage of fat in fat tissue cells.

It is thought that leptin, in an attempt to balance energy levels in the body, could trigger SPARC to limit the storage of fat. SPARC can do this by increasing the formation of scars in fat tissue, which can prevent fat being stored safely in the body. Researchers found that this process could predispose obese patients to type 2 diabetes.

Professor John Wilding, from the University's School of Clinical Science, explains: We tested fat tissue of patients at University Hospital Aintree and found that an increase in leptin also increases SPARC levels, which reduces the safe storage of fat through the development of abnormal tissue scarring. Scarring of fat tissue is known to increase as we gain weight and we found that this is exacerbated by leptin, as well as an increase in insulin, produced by the pancreas.

Dr Katarina Kos, lead author of the research, added: Leptin is produced in fat cells to regulate appetite, but the body becomes resistant to the effects of appetite reduction in obese patients. Leptin continues to increase in response to overall fat mass and promotes scarring through increased SPARC levels. Once scarring occurs, the excess nutritional energy from fat cannot be taken up by fat cells and so remains in the blood and begins to gather around organs. As a result, fat cells of people classified as obese, may not fulfil their natural purpose to store fat.

Diabetes is caused by the cells' inability to respond to insulin, which would normally enable uptake of sugar from the blood. To compensate, the pancreas creates more insulin to clear blood sugar from the circulation. The pancreas becomes exhausted and is unable to produce sufficient insulin to keep up with the demands of the body. This results in the development of type 2 diabetes, which can cause problems such as lack of energy to the cells and, over time, damage to the eyes, kidneys and heart.

The research team, working with the Swedish fast food study group at Linkoping University, also found that weight gain, induced by more than doubling calorie intake through eating 'junk food', causes SPARC levels to increase by 33%. In a further study with the University of Gothenburg, scientists found that a reduced calorie diet can decrease SPARC levels and the stimulus for tissue scarring.

Researchers are now investigating why some people are more prone to fat tissue scarring than others and how further understanding of SPARC could contribute to future treatments for diabetes.

New powder can heal diabetic foot sores

Mon, 03 Aug 2009 16:11:56 PST

( from http://www.rxpgnews.com ) Foot complications, such as open wounds, can be difficult to treat or heal. However, a study has revealed that a new dressing powder, which acts exactly like a layer of skin, is cutting down healing time and reducing the quantum of pain ensuing from serious foot ulcers.

'This new powder comes together, in an amazing flexible film that mimics the wound's surface and helps it to retain moisture and protect the wound, but still allows the right amount of air flow needed for the wound to close,' said study co-author Tracey Vlahovic, Temple University School of Podiatric Medicine.

This wound powder is especially promising for the nearly 24 million Americans diagnosed with diabetes, where diabetic foot ulcers are the leading cause of non-traumatic, lower-limb amputations.

This powder's successful treatment of difficult foot wounds could potentially lead to a reduction in amputation rates.

In a recent American Podiatric Medical Association survey, 18 percent with diabetes reported that they had experienced a foot sore that would not heal.

This includes open sores on the feet as a result of inflammatory bowel disease, diabetes or skin cancer.

The study focused on atypical wounds with irregular shapes and causes. The wounds were treated with the powder dressing once a week for four to eight weeks.

The study ultimately showed that the powder dressing provided a painless, efficient, and protective treatment that assisted in closing the wound.

The powder also helped in preparing the wound for further interventions that are sometimes needed, including options like skin grafts.

These results were presented at the APMA's 97th Annual Scientific Meeting in Toronto July 30-Aug 2.

Lap-band weight-loss surgery can reverse metabolic syndrome in obese teens

Wed, 01 Jul 2009 04:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (June 30, 2009) -- A new study of obese adolescents has shown that laparoscopic gastric banding surgery -- the Lap-Band procedure -- not only helps them achieve significant weight loss but can also improve and even reverse metabolic syndrome, reducing their risk for cardiovascular disease and diabetes.

Metabolic syndrome is defined as a cluster of risk factors -- high blood pressure; low levels of HDL or good cholesterol; excessive abdominal fat; and elevated levels of blood sugar, C-reactive protein and triglycerides -- that increase a person's chances of developing cardiovascular disease or diabetes later in life. The single biggest risk factor is obesity, and metabolic syndrome usually improves when a person loses weight.

The study was led by Drs. Ilene Fennoy, Jeffrey Zitsman and colleagues at NewYork-Presbyterian Morgan Stanley Children's Hospital and Columbia University Medical Center and presented at the annual Endocrine Society meeting in Washington, D.C.

An estimated 17 percent of all American adolescents are obese, and increasing numbers of them also have metabolic syndrome, says Dr. Fennoy, a pediatric endocrinologist at NewYork-Presbyterian Morgan Stanley Children's Hospital, clinical professor of pediatrics at the Columbia University College of Physicians and Surgeons and co-author of the study. Until recently, there have been few treatments capable of helping these young patients lose weight, much less improving their lifelong health prospects. The Lap-Band may well be a useful intervention for tackling teen obesity -- which is why it is so important to investigate the procedure's safety and efficacy in this growing population.

In the new study, Dr. Fennoy and her colleagues followed 24 morbidly obese adolescents between the ages of 14 and 17 who underwent the Lap-Band procedure. The study participants either had a BMI of greater than 40 or greater than 35 if already suffering from diabetes or obesity-related illnesses.

Six months after surgery, they noted a significant drop in participants' BMI, waist circumference, and blood levels of C-reactive protein. These indicators continued to improve among the 12 patients being followed up at the one-year point.

Other measures of metabolic syndrome such as blood lipid and sugar levels, the authors reported, came down quickly in the first six months, with less dramatic changes seen one year after surgery.

Of all the bariatric procedures, she says, the Lap-Band is the most benign, with complication rates of less than 1 percent. The device, inserted via minimally invasive laparoscopic surgery, consists of a simple band to make the stomach smaller and a balloon that can be decompressed when necessary, she explains.

Although it is technically reversible, the procedure should be considered a long-term solution for extreme and intractable obesity.

The Lap-Band is the favored bariatric procedure in Europe, while in the U.S., gastric bypass has been the preferred approach. At present, NewYork-Presbyterian Morgan Stanley Children's Hospital/Columbia University Medical Center is one of a few medical centers offering the Lap-Band option in this country.

The Lap-Band procedure, an approved treatment for adults with extreme obesity, has not yet been thoroughly studied in adolescents. Larger, multicenter studies with longer follow-up periods will be needed, Dr. Fennoy says, to validate the findings of the current study.

Polycystic ovarian syndrome: New light on its causes and its effect on brothers

Tue, 30 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: Researchers have found evidence that chronic disease in either a mother or father can create unfavourable conditions in the womb that are associated with the development of polycystic ovarian syndrome (PCOS) in daughters. In another study, researchers found that brothers of women with PCOS and insulin resistance are themselves at greater risk of developing insulin resistance or diabetes, suggesting that factors associated with the condition can be passed down to sons as well as daughters.

The two studies were presented to the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam heard today (Tuesday).

Associate Professor Michael Davies told a news briefing: We already know from clinical studies of women with reproductive problems that foetal growth restriction is associated with the development of PCOS symptoms in daughters, and that problems during pregnancy and in the way the mother adapts to the metabolic challenge of pregnancy can indicate the future cardiovascular health of both the mother and the child. What we don't know is whether giving birth to a daughter who later develops PCOS is associated with increased, long term cardiovascular disease risk in the mother. Nor do we know whether conditions underlying chronic disease in the father increases the risk of PCOS in the daughter.

Prof Davies, co-director of the Research Centre for the Early Origins of Health and Disease at the University of Adelaide (Australia), looked at records for all female babies who were born and survived between 1973-1976 at The Queen Elizabeth Hospital in Adelaide. He and his colleagues interviewed the daughters to build up a picture of their health and any history of chronic disease in their parents. So far, 998 (63%) have responded, and Prof Davies reported preliminary data up to mid-1975 to the conference.

Sixty-two daughters (6.2% of the group) had a pre-existing diagnosis of PCOS. Mothers of these women tended to have elevated blood pressure during pregnancy. Daughters were nearly eight times as likely to have PCOS if their mothers had it, and they had a slightly higher risk if their mothers smoked during pregnancy. Mothers were 1.6 times as likely to have high blood pressure in later life if their daughters developed PCOS. If their fathers had heart disease or stroke, the daughters also had a higher risk of PCOS: double and three times the risk respectively. A history of diabetes in either parent was not significant.

Prof Davies said: These findings suggest a new pathway for the development of PCOS. We think that factors associated with the pre-existence of cardiovascular dysfunction in the mother or the father, and which operate during pregnancy, may create adverse conditions for the foetus, which alter the metabolic profile of offspring, leading to insulin resistance and reproductive consequences, such as PCOS, for daughters. A family history of diabetes is, therefore, not essential to observe an insulin resistance-related disease in offspring.

He said it was still unclear exactly how the cardiovascular risk in the father affected the daughter. We firstly need to consider the potential role of a common environment; for instance, that families with high levels of obesity (and therefore cardiovascular disease) will also tend to have heavy daughters who are thereby more likely to be affected by PCOS. However, the paternal effect that we saw was independent of the daughter's weight, maternal age, socioeconomic status, maternal smoking, and country of birth, which suggests either a direct genetic effect on the daughter, or an effect of paternal genetic factors that are expressed during pregnancy.

Dr Verena Mattle told the news briefing that her study was the first to show that brothers of women who had PCOS and insulin resistance were themselves more likely to develop insulin resistance or even diabetes or dyslipidaemia (a disruption in the levels of lipids (or fats) in the blood).

Until now, it was not clear whether the male relatives of women with PCOS were at increased risk for the metabolic disorders associated with PCOS, said Dr Mattle, who is chief resident at the University Clinic of Gynecological Endocrinology and Reproduction Medicine in Innsbruck (Austria).

Dr Mattle and her colleagues conducted oral glucose tolerance tests on 15 brothers of sisters with PCOS and insulin resistance (group 1). They also performed a serum analysis to determine lipid levels. As a control, nine brothers of sisters with PCOS but without insulin resistance were included in the study (group 2).

The researchers found that in the first group eight brothers showed an insulin resistance, one was diagnosed with diabetes and six had a normal glucose tolerance test. All nine affected brothers had a body mass index (BMI) between 19-31 kg/m2 and had elevated cholesterol and triglyceride levels. The six unaffected brothers had a BMI between 23-29, and none had high levels of cholesterol or triglycerides. In the second group, no insulin resistance was diagnosed. BMI was between 18-27 and two brothers had elevated cholesterol levels. Although there was a trend towards higher BMI in the first group, Dr Mattle said there was no statistically significant difference in BMIs between the two groups.

Dr Mattle said: These results mean that we should pay attention to the health not only of women with PCOS but also to their brothers as they seem to have an increased risk for the medical problems that make up the metabolic syndrome, such as insulin resistance, diabetes and cardiovascular disease. Our findings are also in accordance with the hypothesis that not only is PCOS is a heritable disease, but that factors associated with it, such as insulin resistance, can be passed down to the next generation of either sex.

She said that it could not be the case that the high BMI by itself could have caused the insulin resistance and diabetes in the affected brothers. There must be a correlation between PCOS and insulin resistance because we could only find brothers with insulin resistance in the group that had sisters with PCOS and insulin resistance, but we couldn't find brothers with insulin resistance in the group that had sisters with PCOS and no insulin resistance. It is known that about 50% of women with PCOS are insulin resistant and also that lean PCOS patients are insulin resistant. The BMI of insulin-resistant and non-resistant brothers were not statistically different.

Dr Mattle and her colleagues are continuing to test brothers of women with PCOS for insulin resistance and lipid levels to collect more data from a larger group. At this stage we would hesitate to say that a genetic inheritance is definitely playing a role in the increased risk of insulin resistance and other, related conditions in these brothers. We need to explore the possible effect of conditions in the womb and also the role of the environment. However, we think our data strongly support the view that brothers of women with PCOS and insulin resistance may have an increased risk of insulin resistance, diabetes and other, adverse metabolic conditions, she concluded

Snoring pregnant women at higher risk for gestational diabetes

Thu, 11 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO --- If you are pregnant and your mate complains your frequent snoring is rattling the bedroom windows, you may have bigger problems than an annoyed, sleep-deprived partner.

A new study from researchers at the Northwestern University Feinberg School of Medicine has found that women who reported frequent snoring during their pregnancy were more likely to develop gestational diabetes -- a condition than can cause health problems for the mother and baby. The study also found pregnancy increases the likelihood that a woman will snore.

This is the first study to report a link between snoring and gestational diabetes.

For the study, 189 healthy women completed a sleep survey at the time of enrollment (six to 20 weeks gestation) and in the third trimester.

Pregnant women who were frequent snorers had a 14.3 percent chance of developing gestational diabetes, while women who did not snore had a 3.3 percent chance. Even when researchers controlled for other factors that could contribute to gestational diabetes such as body mass index, age, race and ethnicity, frequent snoring was still associated with the disease.

Principal investigator Francesca Facco, M.D., a fellow at Northwestern's Feinberg School, will present her findings at the SLEEP 2009 23rd Annual Meeting of the Associated Professional Sleep Societies June 11.

Sleep disturbances during pregnancy may negatively affect your cardiovascular system or metabolism, said Facco, who in August will become an assistant professor of obstetrics and gynecology at the Feinberg School and a maternal and fetal medicine physician at Northwestern Memorial Hospital.

Snoring may be a sign of poor air flow and diminished oxygenation during sleep that can cause a cascade of events in your body, Facco said. This may activate your sympathetic nervous system, so your blood pressure rises at night. This can also provoke inflammatory and metabolic changes, increasing the risk of diabetes or poor sugar tolerance.

The study also showed more women became frequent snorers as their pregnancies progressed. Early in pregnancy, 11 percent of women in the study reported frequent snoring; by the third trimester, the number rose to 16.5 percent. Frequent snoring was defined as snoring three or more nights a week.

Facco said snoring during pregnancy may be triggered by weight gain and edema (a buildup of fluid), which can increase airway resistance. Exactly how the snoring is linked to gestational diabetes is not yet known.

About 4 percent of pregnant women develop gestational diabetes, a condition in which women without previously diagnosed diabetes develop high blood sugar levels during pregnancy. Babies born to mothers with gestational diabetes are at increased risk of problems such as being large for gestational age, which may lead to delivery complications. These babies may also have low blood sugar levels and are at increased risk of becoming obese or developing impaired sugar tolerance or metabolic syndrome later in life.

While gestational diabetes usually resolves after pregnancy, women who develop it are at higher risk for type 2 diabetes later in life.

Facco said further studies are needed to understand the association between snoring and gestational diabetes and to develop interventions to treat sleep disorders during pregnancy.

If snoring is bothering a woman who is pregnant, she should seek a consultation with a sleep specialist, Facco said.

In related study, also to be presented at the SLEEP 2009 meeting, Facco found sleep disturbances such as restless legs syndrome and insomnia increase significantly during pregnancy.

Blocking a muscle growth-limiting hormone protects against obesity and atherosclerosis

Thu, 11 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Knockout of myostatin, a growth factor that limits muscle growth, can decrease body fat and promote resistance against developing atherosclerosis, or hardening of the arteries, according to a new study conducted in mice. The results will be presented Thursday at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

Obesity increases the risk of atherosclerosis, which accounts for 75% of all cardiovascular events, such as heart attacks and strokes, said study co-author Shalender Bhasin, MD, professor of medicine at Boston University School of Medicine and chief of the Section of Endocrinology, Diabetes, and Nutrition at Boston Medical Center. Current strategies aimed at preventing heart disease consist primarily of lowering cholesterol levels, but patients reaching the desired cholesterol levels are still at risk for atherosclerosis if they have other risk factors, such as obesity.

Humans and animals with a mutation in the myostatin gene are extremely muscular and have little fat, past research shows. Also, when the gene encoding myostatin is knocked out in mice, their muscle mass increases.

Bhasin and his co-workers wanted to find out if inhibiting myostatin in mice could resist the development of diet-induced obesity and of atherosclerosis, the buildup of lipid deposits called plaque that can narrow and clog coronary arteries.

The researchers took mice that were genetically altered to develop atherosclerosis and then cross-bred them with myostatin knockout mice. Ten generations later, they had mice who were genetically predisposed to both atherosclerosis and inactivation of myostatin. For controls, they studied mice with a genetic predisposition for atherosclerosis but with intact myostatin gene. All mice received a high-fat diet for 12 weeks, to spur the development of atherosclerosis.

Compared with controls, the mice with deleted myostatin gene had much less body fat and 30 percent lower fasting blood sugar and 80% lower fasting insulin levels, showing a reduction in obesity and a strong resistance to developing diabetes, the authors reported. They also had 50 percent lower low-density-lipoprotein (bad) cholesterol and 30 to 60 percent lower levels of total cholesterol and triglycerides (fats in the blood), respectively. These results indicate protection against the development of atherosclerosis, according to Bhasin.

More research is needed to demonstrate the safety and effectiveness of myostatin inhibitors in humans, Bhasin said. However, he said that that this therapeutic strategy already is possible. Experimental drugs called myostatin blockers or inhibitors are being studied as potential treatments of muscle wasting disorders and limb injuries.

Some currently available nutritional supplements are touted as myostatin inhibitors, but Bhasin said he doubts they are effective.

Childhood obesity increases early signs of cardiovascular disease

Thu, 11 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) By as early as 7 years of age, being obese may raise a child's future risk of heart disease and stroke, even without the presence of other cardiovascular risk factors such as high blood pressure, a new study found. The results were presented at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

The study, conducted by researchers at Nemours Children's Clinic and Dr. Charles DelGiorno, an Endocrine trainee from the Mayo Clinic of Jacksonville, Fla., demonstrates that the unhealthy consequences of excess body fat start very early, said Principal investigator and senior author Nelly Mauras, MD, Chief of Pediatric Endocrinology at Nemours Children's Clinic in Jacksonville, Florida. Obesity alone, the study shows, is linked to certain abnormalities in the blood that can predispose individuals to developing cardiovascular disease early in adulthood.

Our study finding suggests that we need more aggressive interventions for weight control in obese children, even those who do not have the co-morbidities of the metabolic syndrome, Mauras said.

The metabolic syndrome is a cluster of risk factors that raise the risk of developing heart disease, stroke and diabetes. It is increasingly being diagnosed in children as overweight becomes a greater problem. Although debate exists as to its exact definition, to receive a diagnosis of metabolic syndrome, in general you must have at least three of the following: increased waist circumference (abdominal fat), low HDL (good) cholesterol, high triglycerides (fats in the blood), high blood pressure and high blood glucose (blood sugar).

Mauras and colleagues wanted to know if simple obesity could raise cardiovascular disease risk before the metabolic syndrome develops. They therefore screened more than 300 individuals ages 7 to 18 years and included just those without features of the metabolic syndrome. They included 202 subjects in the study: 115 obese children and 87 lean children as controls ~ half were prepubertal and half in late puberty. Obese children had a body mass index (a measure of body fat) above the 95th percentile for their sex, age and height.

To be eligible to participate in the study, the children and adolescents had to have normal fasting blood sugar levels, normal blood pressure and normal cholesterol and triglycerides. Lean controls also could not have a close relative with type 2 diabetes, high cholesterol, high blood pressure or obesity. The latter group proved very difficult to find.

All study participants underwent blood testing for known markers for predicting the development of cardiovascular disease. These included elevated levels of C-reactive protein (CRP), a marker of inflammation, and abnormally high fibrinogen, a clotting factor, among others. Obese children had a 10 fold higher CRP and significantly higher fibrinogen concentrations, compared with age- and sex-matched lean children, the authors reported. These abnormalities occurred in obese children as young as 7-year-olds, long before the onset of puberty.

The results were striking Mauras stated, as the children were entirely healthy otherwise. Although it is not yet known whether early therapeutic interventions can reverse high CRP and fibrinogen, she said it would be prudent for health care providers to advise more aggressive interventions to limit calories and increase activity in healthy overweight children, even before the onset of puberty.

Doctors often do not treat obesity in children now unless they have other features of the metabolic syndrome, she said. This practice should be reconsidered. Further studies by the growup will offer further insight into the effects of therapeutic interventions in these children.

Nicotine induces prediabetes, likely contributes to high prevalence of heart disease in smokers

Thu, 11 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have discovered a reason why smoking greatly increases the risk of heart disease and stroke. Nicotine promotes insulin resistance, also called prediabetes, which is a risk factor for cardiovascular disease, according to the new study, which was presented at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

Additionally, the study authors were able to partially reverse this harmful effect of nicotine in mice by treating them with the nicotine antagonist mecamylamine, a drug that blunts the action of nicotine.

The study, which the National Institutes of Health funded, was conducted by researchers at Charles Drew University of Medicine and Science in Los Angeles and Western University of Health Sciences in Pomona, Calif.

Their results may explain why cigarette smokers have a high cardiovascular death rate, even though smoking causes weight loss, which should protect against heart disease, said the study's lead author, Theodore Friedman, MD, PhD, chief of the endocrinology division at Charles Drew University.

Prediabetes and diabetes are known risk factors for cardiovascular disease. Past studies show that cigarette smokers tend to be insulin resistant, meaning that their hormone insulin does not work properly. To compensate, their blood glucose (sugar) levels become higher than normal but not yet high enough for diabetes. Smokers also have higher rates of diabetes, but it is not clear whether smoking is the cause, because they could have other risk factors, Friedman explained.

Some studies demonstrate that nicotine and cigarette smoking induce high levels of the stress hormone cortisol. As cortisol excess is known to induce insulin resistance, it has been suggested that glucocorticoids, such as cortisol, are the missing [causative] link between cigarette smoking and insulin resistance, Friedman said.

The new study results suggest this theory is correct, he said. The researchers studied the effects, on 24 adult mice, of twice-daily injections of nicotine for 2 weeks. The mice ate less food than control mice that received injections without nicotine, and they also lost weight and had less fat. Despite this, the mice receiving nicotine developed prediabetes (insulin resistance), which subsequent mecamylamine treatment improved somewhat. These mice also had high cortisol levels in their blood and tissues, and mecamylamine blocked this effect.

Our results suggest that reducing tissue glucocorticoid levels or decreasing insulin resistance may reduce the heart disease seen in smokers, Friedman said. We anticipate that in the future there will be drugs to specifically block the effect of nicotine on glucocorticoids and insulin resistance.

Currently available nicotine antagonists are not specific enough to completely block nicotine's effects or they have bothersome side effects, so better drugs are needed for this purpose, he said.

Postpartum anxiety delays puberty in offspring

Wed, 10 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Hormonal changes early in pregnancy cause maternal postpartum anxiety and behavior changes that can lead to a delayed onset of puberty in both birth and adoptive daughters, according to a new study conducted in mice. The results will be presented Wednesday at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

Women have an increased rate of anxiety during pregnancy and for 2 years after giving birth, said the study's lead author, Caroline Larsen, PhD, a postdoctoral fellow at the University of Otago in Dunedin, New Zealand.

Postpartum anxiety disorders are poorly understood and difficult to treat, Larsen said. There is growing evidence that untreated anxiety disorder during pregnancy may contribute to premature birth and also can have major and lasting adverse effects on the infant's development and behavior.

Prolactin is a hormone that may protect against anxiety. Recently Larsen and her co-workers found that mice with induced low levels of prolactin in early pregnancy displayed substantial anxiety after they gave birth. Because the researchers also noted that daughters of the anxious mothers had delayed onset of puberty, they conducted the current study to learn what causes this late physical transition to sexual maturation.

Daughters of female mice made anxious by low prolactin were raised either by their birth mother or by a mouse who was not anxious (control mother). Another group consisted of daughters of nonanxious mice, and these mice were raised by either a control mother or an anxious mother. There were at least six mice in each of the four groups. The researchers determined onset of puberty by examining when the vagina opened and noting the time of first estrus (equivalent to the first menstrual cycle in humans).

Remarkably, puberty was still delayed even if the daughters of anxious mothers were raised by nonanxious mice, Larsen said. And delayed puberty also occurred in daughters born to nonanxious mothers who were raised by anxious mothers.

This result demonstrates that hormonal changes in early pregnancy, as well as changes in maternal behavior caused by these hormone changes, can alter brain development in the offspring and delay puberty, she explained. Larsen believes that their work, with further study, may translate to people.

Finding the hormonal mechanisms that trigger the timing of puberty in mice may help identify potential targets for the prevention and treatment of delayed or early puberty in humans, she said.

Late puberty in humans is linked to shortened height and psychological problems that can persist into adulthood.

Our exposure to controversial chemical may be greater than dose considered safe

Wed, 10 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) People are likely being exposed to the commonly used chemical bisphenol A (BPA) at levels much higher than the recommended safe daily dose, according to a new study in monkeys. The results will be presented Thursday at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

BPA is now known to be a potent estrogen, said Frederick vom Saal, PhD, a co-author of the new study and a professor of biological sciences at the University of Missouri-Columbia. Human and animal studies indicate it could be related to diabetes, heart disease, liver abnormalities, miscarriage and other reproductive abnormalities, as well as prostate and breast cancer.

The U.S. Food and Drug Administration (FDA) declared BPA is safe based on estimates that people consume only small amounts each day from food. However, recent research indicated that U.S. adults are exposed to more BPA from multiple sources than previously thought, vom Saal said.

BPA is found in polycarbonate plastic food and beverage containers, such as water and infant bottles, as well as in the epoxy resin lining of cans and other sources. The chemical can leach into food and beverages, according to the National Institutes of Health, which funded the study by vom Saal and colleagues.

Between 8 and 9 billion pounds of BPA are used in products every year, vom Saal said.

In their study, he and his colleagues fed five female adult monkeys an oral dose of BPA (400 micrograms per kilogram of body weight). This amount is more than 400 times higher than the amount that the U.S. Food and Drug Administration (FDA) estimates that human adults are exposed to and 8 times higher than the estimated safe daily amount to consume, according to vom Saal.

Yet the blood levels of biologically active BPA over the next 24 hours were lower in the monkeys than the average levels found in people in the United States and other developed countries, vom Saal said. For levels to be higher in people when measured, their exposure dose must be greater than that given to the monkeys, he explained.

These results suggest that the average person is likely exposed to a daily dose of BPA that far exceeds the current estimated safe daily intake dose, vom Saal said.

He said that BPA exposure must come from many unknown sources, in addition to food and beverage containers. Like drugs, BPA acts in pulses, with each exposure creating a high-level pulse before it is cleared in the urine, according to vom Saal.

The researchers are continuing the study in more monkeys, but vom Saal said they do not expect to get different findings because the data in the first five animals were very consistent. The species of monkey that they used (rhesus) metabolizes BPA similar to humans, he added.

Gene triggers for diabetes found

Wed, 13 May 2009 14:54:57 PST

( from http://www.rxpgnews.com ) Sydney, May 12 - An international team of scientists has identified more than 40 genes, including 25 new ones, that could be factors in triggering type-1 diabetes.

Leading the Asia Pacific arm of the research group, Grant Morahan, professor, Western Australian Institute for Medical Research -, described this as one of the largest ever genetic studies into type-1 diabetes and among 'the most significant discoveries'.

'Where this discovery has much potential is that it could show us how to stop the disease returning by controlling how the risk genes work,' he said.

'This study involved screening DNA samples donated by more than 10,000 people with type-1 diabetes from across the world, and more than 11,000 people without the condition - including more than 2,000 families in which two children have type-1 diabetes.

'What's really surprising about these findings is not only did we find so many new genes, but we've also come across risk factors that are located between genes along the chromosomes, and at least three of these are in what we call 'gene deserts.'

'The purpose of gene deserts is still a scientific mystery, so this discovery could give us an insight into the function of these chromosome regions, as well as clues to how type-1 diabetes develops.'

The international study was funded by United State's National Institutes of Health -, said a WAIMR release.

The research was published in Nature Genetics online on Monday and will feature in the June edition of the journal.

Increased food intake alone explains the increase in body weight in the United States

Fri, 08 May 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Amsterdam, the Netherlands: New research that uses an innovative approach to study, for the first time, the relative contributions of food and exercise habits to the development of the obesity epidemic has concluded that the rise in obesity in the United States since the 1970s was virtually all due to increased energy intake.

How much of the obesity epidemic has been caused by excess calorie intake and how much by reductions in physical activity has been long debated and while experts agree that making it easier for people to eat less and exercise more are both important for combating it, they debate where the public health focus should be.

A study presented on Friday at the European Congress on Obesity is the first to examine the question of the proportional contributions to the obesity epidemic by combining metabolic relationships, the laws of thermodynamics, epidemiological data and agricultural data.

There have been a lot of assumptions that both reduced physical activity and increased energy intake have been major drivers of the obesity epidemic. Until now, nobody has proposed how to quantify their relative contributions to the rise in obesity since the 1970s. This study demonstrates that the weight gain in the American population seems to be virtually all explained by eating more calories. It appears that changes in physical activity played a minimal role, said the study's leader, Professor Boyd Swinburn, chair of population health and director of the World Health Organization Collaborating Centre for Obesity Prevention at Deakin University in Australia.

The scientists started by testing 1,399 adults and 963 children to determine how many calories their bodies burn in total under free-living conditions. The test is the most accurate measure of total calorie burning in real-life situations.

Once they had determined each person's calorie burning rate, Swinburn and his colleagues were able to calculate how much adults needed to eat in order to maintain a stable weight and how much children needed to eat in order to maintain a normal growth curve.

They then worked out how much Americans were actually eating, using national food supply data (the amount of food produced and imported, minus the amount exported, thrown away and used for animals or other non-human uses) from the 1970s and the early 2000s.

The researchers used their findings to predict how much weight they would expect Americans to have gained over the 30-year period studied if food intake were the only influence. They used data from a nationally representative survey (NHANES) that recorded the weight of Americans in the 1970s and early 2000s to determine the actual weight gain over that period.

If the actual weight increase was the same as what we predicted, that meant that food intake was virtually entirely responsible. If it wasn't, that meant changes in physical activity also played a role, Swinburn said. If the actual weight gain was higher than predicted, that would suggest that a decrease in physical activity played a role.

The researchers found that in children, the predicted and actual weight increase matched exactly, indicating that the increases in energy intake alone over the 30 years studied could explain the weight increase.

For adults, we predicted that they would be 10.8 kg heavier, but in fact they were 8.6 kg heavier. That suggests that excess food intake still explains the weight gain, but that there may have been increases in physical activity over the 30 years that have blunted what would otherwise have been a higher weight gain, Swinburn said.

To return to the average weights of the 1970s, we would need to reverse the increased food intake of about 350 calories a day for children (about one can of fizzy drink and a small portion of French fries) and 500 calories a day for adults (about one large hamburger), Swinburn said. Alternatively, we could achieve similar results by increasing physical activity by about 150 minutes a day of extra walking for children and 110 minutes for adults, but realistically, although a combination of both is needed, the focus would have to be on reducing calorie intake.

He emphasized that physical activity should not be ignored as a contributor to reducing obesity and should continue to be promoted because of its many other benefits, but that expectations regarding what can be achieved with exercise need to be lowered and public health policy shifted more toward encouraging people to eat less.

Study: Vibration plate machines may aid weight loss and trim abdominal fat

Fri, 08 May 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Amsterdam, the Netherlands: New research suggests that, if used properly, vibration plate exercise machines may help you lose weight and trim the particularly harmful belly fat between the organs.

In a study presented on Friday at the European Congress on Obesity, scientists found that overweight or obese people who regularly used the equipment in combination with a calorie restricted diet were more successful at long-term weight loss and shedding the fat around their abdominal organs than those who combined dieting with a more conventional fitness routine.

These machines are increasingly found in gyms across the industrialized world and have gathered a devoted following in some places, but there has not been any evidence that they help people lose weight. Our study, the first to investigate the effects of vibration in obese people, indicates it's a promising approach. It looks like these machines could be a useful addition to a weight control package, said the study's leader, Dirk Vissers, a physiotherapist at the Artesis University College and the University of Antwerp in Belgium.

Vissers and his colleagues studied the effects of the Power Plate in 61 overweight or obese people - mostly women - for a year. The intervention lasted six months, after which the scientists advised all the volunteers to do the best they could with a healthy diet and exercise regime on their own for another six months. Body measurements, including CT scans of abdominal fat, were taken at the beginning of the study and after three, six and 12 months.

The researchers divided the volunteers into four groups. One group was prescribed an individually calculated calorie restricted diet. Dietician visits were scheduled every fortnight for the first three months and every month for the second three months. The dieters were asked not to engage in any exercise for the duration of the six-month intervention.

A second group received the same diet intervention, with the addition of a conventional fitness regime. They attended supervised exercise classes twice a week for an hour and were urged to exercise on their own a third time each week. The sessions included group cycling, swimming, running, step aerobics and some general muscle strengthening exercises.

A third group got the diet intervention plus supervised vibration plate training instead of conventional exercise. They were asked not to do any aerobic exercise during the six-month intervention phase. The physiotherapists gradually increased the speed and intensity of the machine each week, as well as the variety and duration of the exercises from 30 seconds for each of 10 exercises to 60 seconds for each of 22 exercises, such as squats, lunges, calf raises, push-ups and abdominal crunches. The average time spent on the machine was 11.9 minutes per session in the first three months and 14.2 minutes in the second three months.

A fourth group got no intervention. There were no significant differences between the groups in obesity and abdominal, or visceral, fat at the start of the study.

Over the year, only the conventional fitness and vibration groups managed to maintain a 5% weight loss, which is what is considered enough to improve health, Vissers said.

During the first six months, the diet only group lost about 6% of their initial body weight, but could not maintain a 5% weight loss in the subsequent six months. The group that got diet plus conventional fitness lost about 7% of their initial body weight in the first six months, but they didn't put much of it back on and by the end of the study, they had managed to keep off a 6.9% loss. The vibration group lost 11% of their body weight during the intervention phase and by the end of the follow-up period they had maintained a 10.5% loss. The control group gained about 1.5% of their original body weight.

The vibration group lost 47.8 square centimetres of visceral fat during the first six months and still had a loss of 47.7 square centimetres at 12 months. Visceral fat shrank by 17.6 square centimetres in the conventional fitness group in the first six months, but by the end of the year, it was only 1.6 square centimetres less than at the beginning. The diet group had a visceral fat loss of 24.3 square centimetres after six months and 7.5 square centimetres after a year.

These are very encouraging results, but it doesn't mean people trying to lose weight can ditch aerobic exercise and jump on the vibration plate instead. They still need a healthy diet and aerobic exercise, but this could be a viable alternative to weight lifting, Vissers said, explaining that the plate works by making muscles rapidly contract, which builds lean muscle mass.

People say vibration machines are fitness for lazy people. It may feel like a short cut, but if it's easy, you are not doing it properly, he added. Supervision in the beginning is imperative and the longer the better. What we see in gyms very often - people just standing on the machine holding the handles - is not going to do anything.

Vissers said further research on a larger group of obese patients is needed to confirm how beneficial the machines are. His team is also planning to study why vibration seems to be more effective than aerobic exercise in trimming visceral fat, including whether increased blood flow to the abdomen and hormonal response to vibration might play a role in more efficient fat breakdown. His study was funded by the Artesis University College of Antwerp.

Humanin peptide linked to neuronal cell survival and regulation of glucose metabolism

Wed, 22 Apr 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Recent studies have shown that the mitochondrial peptide Humanin (HN) protects against neuronal cell death such as happens in Alzheimer's disease. Now, in a study presented April 22 at Experimental Biology 2009 in New Orleans, Dr. Nir Barzilai reports that a small infusion of HN is the most potent regulator of insulin metabolism that his research team has ever seen, significantly improving overall insulin sensitivity and sharply decreasing the glucose levels of diabetic rats.

The finding is the first evidence of a role for HN in glucose metabolism and provides new insight into how this metabolism may be involved in the development of seemingly diverse age-related diseases such as Type 2 Diabetes Mellitus and Alzheimer's. The finding also provides support for the growing understanding that the brain (not just the pancreas, liver and other peripheral organs) is heavily involved in glucose metabolism.

Furthermore, says Dr. Barzilai, the Ingeborg and Ira Leon Rennert Chair of Aging Research and Director of the Institute for Aging Research at the Albert Einstein College of Medicine, the power of HN on insulin action suggests a new therapeutic approach to diabetes. Further understanding of how HN interactions with the growth hormone/insulin-like growth factor system may also lead to strategies to protect against age-related diseases including Alzheimer's.

Dr. Barzilai's presentation at Experimental Biology 2009 is part of the scientific program of the American Society for Biochemistry and Molecular Biology.

Dr. Barzilai is internationally known as a leading discoverer of longevity genes, especially those he has identified in a well-established group of almost 500 Ashkenazi Jews, aged 95 to 112, and their families. Last year, he reported that some of the oldest in this group have mutations in the gene for insulin-like growth factor 1 (IGF-1) receptor, genetic alterations that have been shown to prolong life span in worms and some mammals. In this Experimental Biology presentation, he reports that, while the production of HN generally decreases as people age, it decreases less in the centenarians and is the highest in their offspring. Studies are now underway at the Institute for Aging Research to determine if the centenarians have a mutation in the HN gene in the mitochondria.

How do these genes fit together? Although there is still much to learn, says Dr. Barzilai, his team increasingly understands how HN interacts with the GH/IGF system. In earlier studies, the team found that insulin-like growth factor binding protein-3 (IGFBP-3) binds Humanin and tempers its effects on promotion of cell survival.

In this new study, the effects of HN on insulin action also were found to be tempered by IGFBP-3. Inhibiting IGFBP-3 allowed the peptide to exert a more potent effect. That suggests a drug target, says Dr. Barzilai.

He says that in this preclinical testing period, it is still too soon to know how HN would perform in humans, but he believes the naturally occurring peptide's ability to preserve cells is promising. One concern of anti-diabetic drugs is increased risk for cardiovascular disease. When Dr. Barzilai's team administered Humanin to rats before or after they were induced to have heart attacks, however, the area of infarction (area of dead cells caused by lack of blood) actually decreased by almost 50 percent, compared to that in rats not given the peptide.

Evidence mounts that short or poor sleep can lead to increased eating and risk of diabetes

Tue, 21 Apr 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Laboratory and epidemiological studies continue to show that sleep curtailment and/or decreased sleep quality can disturb neuroendocrine control of appetite, leading to overeating, and can decrease insulin and/or increase insulin resistance, both steps on the road to Type 2 diabetes.

On April 22, at the Experimental Biology 2009 meeting in New Orleans, a panel of leading sleep researchers describes recent and new studies in this fast growing field. The session is part of the scientific program of the American Association of Anatomists (AAA).

Short sleep, poor sleep: novel risk factors for obesity and for type 2 diabetes.

Dr. Eve Van Cauter, University of Chicago, is a specialist in the effect of circadian rhythms on the endocrine system and has conducted several studies in which short-term sleep restriction damaged the body's ability to regulate eating by lowering levels of leptin, the hormone that tells the body when it has had enough. In the AAA symposium, Dr. Van Cauter describes other recently published studies from her group, one showing that only three days sleep disruption is sufficient to increase insulin resistance in humans (thus causing the body to need higher levels of insulin) and a large epidemiological study showing that short sleep over a five year period causes an increase in systolic blood pressure.

Dr. Van Cauter also describes work in other laboratories, such as a multi-center study, headed by Dr. Sanjay Patel, Case Western Reserve Medical School, in which thousands of older patients wore wrist monitors 24 hours a day, allowing researchers to objectively document how long and well they slept instead of relying on self reports. Some scientists and clinicians had believed that the relationship of short/poor sleep and obesity was important in children and adults but waned with age. Dr. Van Cauter says this study found that short/poor sleep was associated with obesity regardless of age.

Energy metabolism during chronic sleep deprivation: sleep less, eat more, don't gain weight, yet show signs of progression toward diabetes.

Panel member Dr. Michael Koban, Morgan State University, reports a new study in which sleep restriction in rats led to glucose intolerance, a prediabetic state in which the blood glucose remains higher than normal after glucose challenge. Significantly, this is the first rodent study of sleep deprivation in which there was no association between glucose dysregulation and weight gain.

For 13 days, the rats were kept awake 20 of every 24 hours, then returned to their cages where they could sleep. As in a number of other studies of sleep deprivation or poor sleep in humans and rats, the sleep restricted rats greatly increased their consumption of food, in this case a human food supplement laced with chocolate, which rats love and which allowed for a more precise measure of consumption than rat chow, which often gets strewn around like bird seed in a feeder. Control rats allowed to sleep as much as they wanted also had access to the same treat, but ate less.

Significantly, while the sleep-deprived rats ate substantially more than well-rested rats, they did not gain weight. This was due, says Dr. Koban, to an increase in energy metabolism. The resting metabolism of the sleep-deprived rats rose sharply, coupled with rapid mobilization of hepatic and muscle glycogen followed by reduction in abdominal white adipose tissue.

Further studies are now underway in the Koban laboratory that more closely mimics chronic sleep deprivation in humans. The researchers believe that extending sleep restriction will produce more pronounced glucose intolerance in which glucose levels do not return to normal levels for a longer period, thus providing more evidence that not sleeping enough could lead to diabetes in humans. The researchers also are looking for mechanisms to explain the change in metabolism related to sleep deprivation and the dissociation between weight gain and glucose dysregulation and insulin resistance.

Embargoed news from Annals of Internal Medicine

Mon, 20 Apr 2009 04:00:00 PST

( from http://www.rxpgnews.com ) EARLY RELEASE ARTICLE: Article available online April 21 (in print June 2)

1. Patient-Tailored Treatment Regimens May Have a More Positive Impact than Strict Glycemic Control in Managing Type 2 Diabetes

Physicians routinely emphasize tight glycemic control for patients with type 2 diabetes. However, tight glycemic control may require highly complex treatment regimens that can result in frustration, non adherence, and financial stress for some patients. Researchers reviewed large trials in which type 2 diabetic patients were randomly assigned to either tight or loose targets for glycemic control. Based on the evidence, the researchers developed practical suggestions for managing these patients. According to the authors, physicians should support healthy lifestyles, preventive care, and cardiovascular risk reduction in patients with type 2 diabetes. Physicians should individualize drug treatment approaches so that patients can aim for a blood glucose level that best balances the burden of medication with the benefit in reducing symptoms and complications of diabetes. The authors advocate for tools and tactics that encourage patient involvement in treatment decisions, as these may lead to treatment programs that are both evidence-based and consistent with patients' lifestyles and informed values.

2. Universal Insurance Coverage May Reduce Race-based Health Care Disparities

Does access to health insurance reduce race-based health care disparities? To find out, researchers studied National Health and Nutrition Examination Survey data collected from 1998 to 2006 on more than 9,000 adults with chronic conditions such as hypertension, diabetes, or coronary heart disease. The authors assessed changes over time in chronic disease control as measured by blood pressure, hemoglobin A1c, and LDL cholesterol. These measures were then compared by race, ethnicity, and education. Finally, the authors compared sociodemographic differences above and below the age of eligibility for Medicare. The researchers found that while control of hypertension, diabetes, and coronary heart disease improved over the years, gaps in disease control between white and nonwhite patients did not change. However, the gaps narrowed after age 65 when Medicare insurance begins. The authors conclude that universal health insurance could reduce disparities in care among patients from different racial or ethnic groups.

3. The USPSTF Reaffirms its Recommendations on Physician Counseling and Interventions to Prevent Tobacco Use

Smoking increases risks for heart disease, lung disease, and cancer. In pregnant women, smoking also increases the risk for miscarriage, low birthweight, and premature delivery. Quitting smoking reduces these risks. Primary care physicians have a unique opportunity to counsel adult patients about preventive healthcare, including quitting smoking. In 2003, the USPSTF concluded that the benefits of smoking cessation interventions by primary care physicians outweighed the risks. Following a review of published research since then, the USPSTF reaffirms its 2003 recommendation on counseling to prevent tobacco use. Clinicians should ask all adults about tobacco use and provide tobacco cessation interventions for those who use tobacco products. For pregnant women, clinicians should ask about tobacco use and provide pregnancy-tailored counseling for those who smoke.

4. Considering Genetic and Other Risk Factors May Help Identify Patients at Highest Risk for Type 2 Diabetes

Gene therapy appears safe to regenerate gum tissue

Tue, 07 Apr 2009 04:00:00 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich.---Scientists at the University of Michigan have developed a method of gene delivery that appears safe for regenerating tooth-supporting gum tissue---a discovery that assuages one of the biggest safety concerns surrounding gene therapy research and tissue engineering.

Gene therapy is an accepted, viable therapeutic concept, but safety is a major hurdle, said William Giannobile, professor at the U-M School of Dentistry. The most notable incident highlighting the safety concerns of gene therapy research and treatment occurred several years ago when a teenager died when given the adenovirus during a gene therapy clinical trial at the University of Pennsylvania.

The U-M therapy also uses the adenovirus, Giannobile said, but the big difference in the U-M approach lies in the local application and much lower dose. Instead of injecting the genes into the blood vessels, where they can then travel through the bloodstream and result in unexpected and sometimes fatal reactions, U-M scientists put the genes on a localized area, directly on the tissue during surgery much like a paste.

What the U-M study showed is (the topical method) is very well contained and doesn't distribute throughout the body, said Giannobile, who also directs the Michigan Center for Oral Health Research and has an appointment at the U-M College of Engineering's Department of Biomedical Engineering. This approach alleviates the safety concern about negative reactions within the body.

When the teenager died, it got into his bloodstream and he reacted to it. It was tragic. This is the first study of periodontal disease therapy that demonstrates the distribution of these genes is very safe, suggesting that it could be used in the clinic for clinical application.

Our study doesn't look at all the safety concerns, but certainly this is very important to the field. The two clinical applications to date where it shows potential are periodontal disease and diabetic wounds. Maybe the reason for this is that both diseases result from a compromised or a defective healing environment.

The next step for the U-M team is to use the new gene delivery approach in human clinical trials, Giannobile said. The planning stages for these studies will commence in the next year.

The paper, called Adenovirus Encoding Human Platelet-Derived Growth Factor-B Delivered to Alveolar Bone Defects Exhibits Safety and Biodistribution Profiles Favorable for Clinical Use, is partially available online. It's scheduled to appear in the May issue of the journal Human Gene Therapy. Co-authors include Po-Chun Chang, Joni Cirelli, Yang-Jo Seol, Qiming Jin, Jim Sugai, Nisha D'Silva and Theodora Danciu. The study was supported by the National Institutes of Health and the AO Foundation.

Scientists closer to understanding how to control high blood sugar

Wed, 18 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich.---Scientists are closer to understanding which proteins help control blood sugar, or glucose, during and after exercise. This understanding could lead to new drug therapies or more effective exercise to prevent Type 2 diabetes and other health problems associated with having high blood sugar.

Insulin resistance happens when insulin produced by the body doesn't properly stimulate the transport of glucose into the cells for energy. Too much glucose in the bloodstream can cause a host of medical problems, including Type 2 diabetes, said Gregory Cartee, professor at the University of Michigan School of Kinesiology.

Insulin and muscle contractions are the two most important stimuli to increase glucose transport into muscle cells. Cells then use the glucose for energy. However, scientists aren't entirely sure how this works.

Cartee and colleague Katsuhiko Funai, a graduate student researcher in kinesiology, looked at how two different proteins believed to be important in stimulating glucose transport react to two different enzymes also related to glucose transport. The goal of the study was to understand the contribution of the two proteins, AS160 and TBC1D1, in skeletal muscle stimulated by insulin.

We're trying to rule out or rule in which proteins are important with exercise, Cartee said.

The results suggest that the protein TBC1D1 was more important for exercise-stimulated glucose transport and suggested that the second protein, AS160, might be less important for this effect of exercise. By focusing on the protein that works best---in this case, TBC1D---scientists can develop ways to make that protein work better for insulin-resistant people.

Insulin resistance is a huge public health problem that affects millions of people, Cartee said.

Almost all people with Type 2 diabetes have muscle insulin resistance, he said. This doesn't cause diabetes by itself, but it's an essential component that contributes to Type 2 diabetes. This impacts millions of people. Even for people who aren't diabetic, insulin resistance is associated with lots of health problems.

In the longer term, people who are insulin resistant, or whose muscle don't respond normally to insulin, are more likely to get Type 2 diabetes, Cartee said.

The muscles seems to have the machinery to respond to exercise, even though they aren't responding to insulin normally, he said. If we understood how exercise worked we could develop more effective exercise protocols. In others who can't exercise, we could figure out a drug therapy or something else for insulin control.

The next step is to study what exactly TBC1D1 does to promote glucose transport during and after exercise.

Obesity gene associated with susceptibility to polycystic ovary syndrome

Mon, 16 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have shown that a gene implicated in the development of obesity is also associated with susceptibility to polycystic ovary syndrome (PCOS). The FTO gene has recently been shown to influence a person's predisposition to obesity, and is now the first gene to be associated convincingly with susceptibility to PCOS(1). Carried out by Dr Tom Barber and colleagues from the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Imperial College London, this research is the first evidence to show a genetic link between obesity and PCOS. The results are being presented at the annual Society for Endocrinology BES meeting in Harrogate.

PCOS is a common condition affecting up to 1 in 10 women of child-bearing age. PCOS affects the ovaries and is characterised by irregular periods, excessive hair growth and is a common cause of infertility. PCOS is strongly associated with obesity, and it is thought that the prevalence of PCOS will increase with rising levels of obesity. The FTO gene is known to influence weight. There are two versions of this gene, one of which is associated with increased weight gain and susceptibility to development of obesity(2).

Dr Tom Barber and colleagues are interested in working out the genetic causes of PCOS and its metabolic consequences. Given the association between PCOS and obesity, they investigated whether variants of the FTO gene also influence susceptibility to PCOS. To this end, they analysed the type of FTO gene carried by 463 PCOS patients and 1336 female population controls. They found that the type of FTO gene a person carried significantly influenced their susceptibility to PCOS. In fact, the version of the gene which is associated with increased weight gain is also associated with PCOS. The data suggest that FTO variants influence PCOS-susceptibility via an effect on fat mass. This is the first gene to be associated convincingly with susceptibility to PCOS and provides genetic evidence to corroborate the well established link between PCOS and obesity.

Researcher Dr Tom Barber said:

Polycystic ovary syndrome is an incredibly common condition affecting 1 in 10 women of reproductive age and is a leading cause of infertility. It is a genetic condition and one that is strongly associated with obesity; it is therefore of huge relevance for women given today's obesity epidemic. Our research shows that a variant of the FTO gene that has previously been shown to be associated with obesity also influences susceptibility to polycystic ovary syndrome. These data provide the first genetic evidence to corroborate the well documented association between these two conditions. Our future work will focus on elucidating the underlying mechanisms of polycystic ovary syndrome and its metabolic consequences with the hope of understanding how this common condition develops. This in turn will instruct future therapeutic developments for women who suffer from polycystic ovary syndrome.

Hormone offers promise as fertility treatment

Mon, 16 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) New research suggests the hormone kisspeptin shows promise as a potential new treatment for infertility. The research is being presented at the annual Society for Endocrinology BES meeting in Harrogate. Scientists led by Dr Waljit Dhillo from Imperial College London, have shown that giving kisspeptin to women with infertility can activate the release of sex hormones which control the menstrual cycle. This research could lead to a new fertility therapy for women with low sex hormone levels.

Kisspeptin is a product of the KISS-1 gene and is a key regulator of reproductive function. Animals and humans lacking kisspeptin function do not go through puberty and remain sexually immature. In a previous study, Dr Waljit Dhillo and colleagues showed that kisspeptin treatment leads to the production of sex hormones in fertile women; they have now extended their research to look at the effects of kisspeptin in women whose periods have stopped due to a hormone imbalance.

In this study, funded by the Medical Research Council, The Wellcome Trust and National Institute for Health Research, a group of ten women who were not menstruating and infertile, were injected with either kisspeptin (n=5) or saline (control, n=5). Blood samples were then taken to measure their levels of luteinising hormone (LH) and follicle stimulating hormone (FSH), two sex hormones essential for ovulation and fertility. Kisspeptin led to a 48-fold increase in LH and 16-fold increase in FSH, when compared to the control treatment.

This is the first study to show that kisspeptin can stimulate sex hormones in women with infertility and presents kisspeptin as a potential new therapy for human infertility.

Researcher Dr Waljit Dhillo from the Department of Investigative Medicine at Imperial College London said:

Infertility is a devastating condition that affects millions of couples worldwide. This research shows that kisspeptin offers huge promise as a treatment for infertility. From our previous results, we know that kisspeptin can stimulate release of reproductive hormones in healthy women. We have now extended this research to show that kisspeptin treatment has the same effect in women with infertility. In fact, our current data show that kisspeptin causes a greater increase in luteinising hormone production in non-menstruating women, than that in fertile women in the previous study. This is a very exciting result and suggests that kisspeptin treatment could restore reproductive function in women with low sex hormone levels. Our future research will focus on determining the best protocol for repeated kisspeptin administration with the hope of developing a new therapy for infertility.

Team-based diabetes care fetches more value for dollar

Thu, 26 Feb 2009 05:00:00 PST

( from http://www.rxpgnews.com ) Diabetes patients undergoing team-based care do not save more in treatment costs under Medicare and Medicaid than other patients, but they are healthier, according to a recent study.

Chronic conditions impose a substantial financial burden on patients, payers and employers, said Dennis Scanlon, professor of health policy and administration, Penn State, and lead author of the study. Assessing the financial impact of chronic care management strategies remains a key health policy issue.

The researchers compared Medicaid patients with diabetes who received team-based care with those who did not. The aim of the study was to determine whether multidisciplinary team-based care reduces medical payments and improves quality for the Medicaid enrollees.

Individuals with chronic conditions account for disproportionately high health cost and often experience losses in productivity, notes Scanlon. But on average these patients receive only 56 percent of recommended care according to recent studies.

The Penn State researchers analyzed data between 1997 and 2005 from Medicaid and Medicare claims and payments one year before and after intervention for patients at CareSouth, a federally qualified community health center serving 10 clinics in and around Hartsville, South Carolina.

Our analysis suggests that patients enrolled in the CareSouth program did not experience significantly lower total Medicare and Medicaid costs than similar patients who did not receive team-based care, said Scanlon, whose work is funded by the California Health Care Foundation.

Statistical analyses also suggest that over time there is significant improvement in systolic blood pressure, body mass index and hemoglobin A1C among CareSouth patients.

Scanlon finds the improvement in care without significant increases in drug costs and improvement in the body mass index unusual. He believes that better lifestyle management could be a reasonable explanation.

The researchers caution that the study was only able to include data for a short period of time after team-based care was initiated. Therefore, it is possible that a multi-year study could show longer-term savings associated with the program. Still, Our findings suggest that even if longer-term savings do not materialize, Medicaid and Medicare patients in this study received greater value for their dollars in the CareSouth sites after the intervention, Scanlon explained.

Scanlon and his colleagues first identified 199 patients with type 2 diabetes -- from a sample of 2,572 patients -- in whom the disease had been diagnosed less than a year before the start of intervention. The control group was 1,868 patients who had been diagnosed with the disease more than a year after intervention.

Our objective was to assess the impact of CareSouth's program on short-term Medicaid payments, as well as Medicare payments by those eligible for that Federal insurance program, and on key clinical diabetes indicators, explained Scanlon, whose findings appeared in a recent issue of

PAI-1 is the link between diabetes and cardiovascular disease

Wed, 25 Feb 2009 00:30:27 PST

( from http://www.rxpgnews.com ) Researchers at the University of Vermont Cardiovascular Research Institute, Colchester, Vermont have found that increased expression in the heart of plasminogen activator inhibitor type-1 (PAI-1) is profibrotic. The results, which appear in the March 2009 issue of Experimental Biology and Medicine, implicate PAI-1 overexpression, known to accompany insulin resistance and type 2 diabetes, as a factor contributing to the high incidence of heart failure after myocardial infarction in people with diabetes. The research team, Dr. A.K.M. Tarikuz Zaman, a research associate, Mr. Christopher J. French, medical and graduate student, Dr. David J. Schneider, Professor of Medicine and Director of the Cardiology and Vascular Biology Units, and Dr. Burton E. Sobel, Professor of Medicine and Director of the Cardiovascular Research Institute, performed studies in 10 week old mice subjected to coronary occlusion. Controls and PAI-1 overexpressing mice congenic on a C57BL6 background had comparable PAI-1 content in left ventricular myocardium despite a marked elevation of PAI-1 in plasma in the latter. 6 weeks after coronary occlusion the PAI-1 overexpressing mice exhibited a 2-fold increase in left ventricular (LV) PAI-1 content. Histochemical analysis demonstrated 33% more LV fibrosis as well. The increased fibrosis associated with increased PAI-1 was accompanied by functional derangements including diminished LV wall thickness in both diastole and systole, increased end systolic LV dimensions, depressed fractional shortening, a greater impairment of LV segmental function, and greater transmitral E-wave amplitude.

In summary, overexpression of PAI-1 in the heart altered the response of the left ventricle to myocardial infarction. It led to increased expression of PAI-1 late after coronary occlusion accompanied by increased fibrosis and functional derangements indicative of both systolic and diastolic dysfunction. Dr. Sobel said that "in concert with our previously reported findings demonstrating increased expression of PAI-1 in the heart in transgenic mice rendered insulin resistant, these results suggest that the markedly increased incidence and severity of heart failure following myocardial infarction in patients with insulin resistance and type 2 diabetes may reflect in part adverse consequences of increased PAI-1 expression in the heart predisposing to fibrosis and impairment performance of the left ventricle."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "these elegant studies by Dr. Sobel and colleagues provide substantial insight into the mechanisms by which type 2 diabetes, with the resulting increase in PAI-1 in the heart, can lead to increased incidence and severity of heart failure following myocardial infarction. This is a major step forward in our understanding of the linkage between diabetes and cardiovascular disease".