RxPG News : Metabolism

Overweight people will stay that way for ever

Wed, 27 Jul 2011 08:14:38 PST

( from http://www.rxpgnews.com ) It's bad news for overweight people. A 55-year study in Britain has found out that once people gain weight, they can never return to their original size.

Of the 12 million Britons who diet every year, less than 10 percent succeed in losing significant amounts of weight - with most putting it back on within a year.

The national survey by the Medical Research Council followed 5,362 men and women since their birth in 1946, and 20,000 people born in 1958, the Daily Express reported.

The study measured weight and blood pressure and assessed the lifestyles of the people.

'Both groups began increasing in weight in the 1980s and since then people have been increasing in mass all through life,' Rebecca Hardy of the council was quoted as saying.

'For men it goes up steadily through life. For women it starts slowly and accelerates in the mid-30s. Once people become overweight they continue relentlessly upwards - hardly ever going down.'

The study, however, adds that dieting has its own benefits.

People who try to lose weight tend to eat better and exercise more, leading to increased fitness and lower blood pressure.

The latest health survey in Britain says that in 2009, 14 percent of children and 25 percent of adults were obese.

Your shampoo could be making you fat

Tue, 12 Jul 2011 17:11:28 PST

( from http://www.rxpgnews.com ) Eating healthy and exercising regularly are good enough for sloughing off the pounds. But what if your body acts otherwise? Doctors have found that chemical compounds in cosmetics disrupt the body's natural weight control system.

Emerging evidence suggests that a more sinister reason than food and activity could be behind obesity. They are the so-called 'chemical calories' lurking in beauty products, including innocuous looking shampoo, body lotions and soap.

Doctors at the Mount Sinai Medical Center in New York claim that phthalates, chemical ingredients in 70 percent of cosmetics and household cleaning products, have been shown to disrupt the body's natural weight control system.

Exposure to phthalates through daily use may be linked to childhood obesity and weight problems in adults, the scientists warned, reports the Daily Mail.

In their long-term study on girls living in the inner city area of East Harlem, New York, Mount Sinai team measured exposure to phthalates by analysing the children's urine.

'The heaviest girls have the highest levels of phthalates in their urine,' says Prof Philip Landrigan, paediatrician and study author from Mount Sinai. 'It goes up as the children get heavier, but it's most evident in the heaviest kids.'

Phthalates have been widely used as gelling agents in cosmetics, cleaning products and to make plastic bottles for more than half a century, but it has only just come to light that there may be possible health risks.

Another substance, Bisphenol-A -, also present in containers and bottles, has also been found to be rich in 'chemical calories.'

Billed as 'endocrine disruptors,' they are absorbed into the body affecting the glands and hormones that regulate numerous bodily functions.

It's not just girls who seem susceptible to the phthalate effect. In 2007, researchers at the University of Rochester School of Medicine, US, found the same class of chemicals were contributing to abdominal obesity and insulin resistance, a precursor to diabetes, in men.

Rochester scientists analysed the urine, blood samples and other data of 1,451 men. They found that those with the highest level of phthalates in their urine had more belly fat and insulin resistance.

They suggested that depressed testosterone levels due to chemicals was the underlying cause of their weight gain.

--Indo-Asian News service

St/rn/vt

This asthma drug can burn your fat

Wed, 08 Jun 2011 13:18:05 PST

( from http://www.rxpgnews.com ) Sydney, June 8 - Formoterol, a new generation asthma drug, has shown great promise in improving fat and protein metabolism.

Endocrinologist Paul Lee from the Garvan Institute of Medical Research focused his doctoral research on how various hormones affect metabolism. Of key importance is a class of hormones called catecholamines, which regulate heart rate, metabolism and breathing.

Formoterol is a synthetic catecholamine, the metabolic effects of which have not previously been studied in people. Therapy doses given to animals, however, have shown that it stimulates metabolism without affecting the heart.

'We have known for a long time that catecholamine influences the way the body handles nutrients, in particular fat and protein,' said Lee, according to a Garvan statement.

'The generation of drugs before formoterol was exploited in the livestock industry around 20 years ago - to reduce the fat and increase the protein content of meat. Unfortunately, these older drugs also caused a faster heart rate.'

Lee sourced the drug in its oral form, found the dose needed to give a metabolic effect, and gave it to a group of healthy men over a week.

'Energy metabolism increased by more than 10 percent, fat burning increased by more than 25 percent, while protein burning fell by 15 percent,' he said.

'So although whole body metabolism increased, these men burned fat while reducing the burning of protein. That's a good thing because in the long run, these effects may lead to a loss in fat mass and an increase in muscle.

'In this study, all the subjects tolerated the medication well - without any significant increase in heart rate,' concluded Lee.

These findings will be presented at The Endocrine Society's 93rd Annual Meeting in Boston.

Eating less may help you live longer

Tue, 29 Dec 2009 15:05:57 PST

( from http://www.rxpgnews.com ) Going back for a second dessert after your holiday meal might not be the best strategy for living a long, cancer-free life, a new study has confirmed.

University of Alabama-Birmingham - researchers have shown exactly how restricted calorie diets, specifically in the form of restricted glucose -, help human cells live longer.

This discovery could help lead to drugs and treatments that slow human ageing and prevent cancer.

'Our hope is that the discovery that reduced calories extend the lifespan of normal human cells will lead to further discoveries of the causes for these effects in different cell types...,' said Trygve Tollefsbol, researcher at the Centre for Aging and Comprehensive Cancer Centre UAB.

'We would also hope for these studies to lead to improved prevention of cancer as well as many other age-related diseases through controlling calorie intake of specific cell types,' he added.

Tollefsbol and colleagues used normal human lung cells and pre-cancerous human lung cells that were at the beginning stages of cancer formation.

Eating less may help you live longer

Both sets of cells were lab grown and received either normal or reduced levels of glucose. As the cells grew over a period of a few weeks, researchers monitored their ability to divide, and tracked how many cells survived over this period.

They found that the normal cells lived longer, and many of the precancerous cells died, when given less glucose. Gene activity was also measured under the same conditions, said a UAB release.

'Western science is on the cusp of developing a pharmaceutical fountain of youth,' said Gerald Weissmann, medical expert and editor-in-chief of the Federation of American Societies for Experimental Biology - Journal, which published these findings.

Oral bisphosphonate related jaw necrosis

Thu, 01 Jan 2009 12:05:19 PST

( from http://www.rxpgnews.com ) Researchers at the University Of Southern California, School Of Dentistry release results of clinical data that links oral bisphosphonates to increased jaw necrosis. The study is among the first to acknowledge that even short-term use of common oral osteoporosis drugs may leave the jaw vulnerable to devastating necrosis, according to the report appearing in the January 1 Journal of the American Dental Association (JADA).

Osteoporosis currently affects 10 million Americans. Fosomax is the most widely prescribed oral bisphosphonate, ranking as the 21st most prescribed drug on the market since 2006, according to a 2007 report released by IMS Health.

"Oral Bisphosphonate Use and the Prevalence of Osteonecrosis of the Jaw: An Institutional Inquiry" is the first large institutional study in the U.S. to investigate the relationship between oral bisphosphonate use and jaw bone death, said principal investigator Parish Sedghizadeh, assistant professor of clinical dentistry with the USC School of Dentistry.

After controlling for referral bias, nine of 208 healthy School of Dentistry patients who take or have taken Fosamax for any length of time were diagnosed with osteonecrosis of the jaw (ONJ). The study's results are in contrast to drug makers' prior assertions that bisphosphonate-related ONJ risk is only noticeable with intravenous use of the drugs, not oral usage, Sedghizadeh said. "We've been told that the risk with oral bisphosphonates is negligible, but four percent is not negligible," he said.

Most doctors who have prescribed bisphosphonates have not told patients about any oral health risks associated with the use of the drugs, despite even short-term usage posing a risk due to the drug's tenacious 10-year half life in bone tissue. Lydia Macwilliams of Los Angeles said no one told her about the risk posed by her three years of Fosamax usage until she became a patient of Sedghizadeh at the School of Dentistry. "I was surprised," she said. "My doctor who prescribed the Fosamax didn't tell me about any possible problems with my teeth."

Macwilliams was especially at risk for complications because she was to have three teeth extracted. The infection is a biofilm bacterial process, meaning that the bacteria infecting the mouth and jaw tissues reside within a slimy matrix that protects the bacteria from many conventional antibiotic treatments, and bisphosphonate use may make the infection more aggressive in adhering to the jaw, Sedghizadeh said. The danger is especially pronounced with procedures that directly expose the jaw bone, such as tooth extractions and other oral surgery. After her extractions, two of the three extraction sites had difficulty healing due to infection, Macwilliams said. Luckily, with treatment as well as the rigorous oral hygiene regimen USC dentists developed especially for patients with a history of bisphosphonate usage, the remaining sites slowly but fully healed. "It took about a year to heal," she said, "but it's doing just fine now."

Sedghizadeh hopes to have other researchers confirm his findings and thus encourage more doctors and dentists to talk with patients about the oral health risks associated with the widely used drugs. The results confirm the suspicions of many in the oral health field, he said. "Here at the School of Dentistry we're getting two or three new patients a week that have bisphosphonate-related ONJ," he said, "and I know we're not the only ones seeing it."

Burning fat can lead to a longer life in worms

Tue, 11 Nov 2008 15:40:52 PST

( from http://www.rxpgnews.com ) Washington, Nov 7 - Burning fat can lead to a longer life at least in case of worms, according to a new study.

A fat-burning enzyme in C. elegans increases its activity after the worm's reproductive stem cells stop proliferating, and the result is a longer lifespan, said Meng Wang of Harvard Medical School, Boston, and colleagues.

Their findings offer a tantalising glimpse into how regulation of metabolism, lifespan and reproduction are linked, a relationship that longevity studies are increasingly focusing on, said Ting Xie a colleague.

Wang and colleagues show that reproductive stem cells in adult worms actively control levels of the lipase K04A8.5, which reduces intestinal fat. When the stem cells stop proliferating, levels of lipase rise significantly and zap the fat, said a Harvard release.

Worms with the lipase activated in the intestine lived 24 percent longer than their siblings, the researchers found.

The report appeared in Thursday issue of Science.

New obesity drug, Tesofensine, seems promising

Thu, 23 Oct 2008 14:29:20 PST

( from http://www.rxpgnews.com ) According to trials, a new obesity drug, Tesofensine, which may be launched on the world market in a few years, can produce weight loss twice that of currently approved obesity drugs. The Danish company Neurosearch and a number of researchers at the Faculty of Life Sciences at University of Copenhagen are behind the promising findings.

Tesofensine can produce weight loss twice that of currently approved obesity drugs, and should be studied in phase III trials. These are the conclusions of an Article published early Online and in an upcoming edition of The Lancet, written by Professor Arne Astrup, Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Denmark, and colleagues.

Increased obesity prevalence worldwide, in both developed and developing countries, results in more people with cardiovascular disease, diabetes, musculoskeletal disorders, and cancer. Whilst gastric bypass surgery substantially reduces bodyweight and obesity-related disease, the researchers believe a treatment gap exists between the effectiveness of currently marketed obesity drugs and gastric-bypass surgery. Tesofensine – which inhibits the presynaptic uptake of the neurotransmitters noradrenaline, dopamine and serotonin in the brain – has been shown to be safe and effective in animal models. It also caused unintended weight loss when it was given obese patients with Parkinson's or Alzheimer's disease when it was researched for those conditions. The drug works by suppressing hunger, leading to an energy deficit which burns off excess body fat.

This randomised, placebo-controlled phase II study was done in five Danish obesity management centres, and involved 203 obese patients (body mass index 30-40 kg/m2), weighing a mean of just over 100kg. They were prescribed a limited-energy diet and assigned to tesofensine 0.25mg (52 patients), 0.5 mg (50), 1.0 mg (49), or placebo (52), all once daily for 24 weeks. The primary outcome was percentage change in bodyweight. A total of 161 patients completed the study, and an analysis showed that the mean weight loss recorded for placebo and diet was 2.2kg and for tesofensine 0.25mg, 0.5mg and 1.0mg it was 6.7kg, 11.3kg, and 12.8kg respectively. For the 0.5mg and 1.0mg doses, this represented a weight loss around twice that attained using sibutramine or rimonabant*, the currently-approved therapies in Europe. Blood pressure was increased in the 1.0mg group.The most common side-effects caused by tesofensine were dry mouth, nausea, constipation, hard stools, diarrhoea, and insomnia.

The authors conclude that the 0.5mg dose of tesofensine is more promising than the 1.0mg dose because it produces a similar weight loss with less side-effects. They say: "We conclude that tesofensine 0.5 mg, once daily for 6 months, has the potential to produce twice the weight loss as currently approved drugs; however, larger phase III studies are needed to substantiate our findings."

Can slowing down 'fat burning' genes reduce obesity?

Sat, 04 Oct 2008 14:06:23 PST

( from http://www.rxpgnews.com ) Washington, Oct 4 - Inactivating a pair of key genes involved in 'fat burning' actually increases energy expenditure and helps lower obesity, according to a new study.

Humans and other warm-blooded animals need to continually 'burn fat' in order to maintain body temperature, and it's currently believed that an individual's fat-burning capacity, or thermogenic potential, is connected with obesity risk. In fact, bodybuilders and dieters looking to burn fat commonly use thermogenic supplements like ephedra.

In theory, lowering thermogenesis should increase the chances of obesity, but Leslie Kozak and colleagues at Pennington Biomedical Research Centre found that this may not be the case, according to a release of the centre.

They knocked-out two thermogenic genes in mice, Ucp1 - and Gdm - and then fed the mice a high-fat diet while rearing them at a cool 20 degrees Celsius.

Surprisingly, these mice were actually quite resistant to obesity, which resulted from the mice turning on backup heat generators, so to speak. Lacking Ucp1 and Gdm, genes that have been designed for the efficient production of heat, their white fat cells activated alternate, and more inefficient, fat burning pathways.

In this case the inefficiency was beneficial, as the mice had to burn more fat than normal to stay warm -.

Importantly, after spending 10 weeks at 20 degrees Celsius the mice retained these alternate pathways even after transferring to 28 degrees, suggesting their bodies had adapted to the change.

Thus, Kozak and colleagues noted, fat burning does not necessarily require making thermogenesis easier; by making it harder and forcing the body to use inefficient methods to stay warm, the same goals can be reached.

Single mechanism to explain metabolic syndrome

Mon, 30 Jun 2008 09:00:11 PST

( from http://www.rxpgnews.com ) Many of the 75 million Americans with essential hypertension also develop diabetes and other complications in addition to their high blood pressure, and researchers have discovered a common molecular mechanism in a strain of rat that explains why such metabolic disorders arise together in mammals.

The bioengineering researchers at UC San Diego’s Jacobs School of Engineering also showed that a drug developed for unrelated purposes in humans was effective in counteracting the underlying molecular mechanism in the spontaneously hypertensive rat (SHR), a strain predisposed to develop high blood pressure.

In a paper published June 30 in the online version of Hypertension, Frank DeLano, a research scientist at UC San Diego, and Geert Schmid-Schönbein, a professor of bioengineering, describe how they successfully reversed the SHR animals’ symptoms of high blood pressure, a pre-diabetes condition called insulin resistance, and immune suppression.

H. Glenn Bohlen, a professor in the Department of Cellular and Integrative Physiology at Indiana University Medical School, wrote in an accompanying editorial in Hypertension that the new study will likely be important to people suffering from obesity as well as hypertension. “With the national and international emphasis on obesity and its attendant cardiovascular problems, there is a tendency to forget that essential hypertension affects about the same percentage of humans as does serious obesity and an even higher percentage of the population than does type 2 diabetes mellitus,” wrote Bohlen. “The elegant study by Delano and Schmid-Schönbein points to a potentially very important overlap of an insulin resistance mechanism with hypertension in the spontaneously hypertensive rat (SHR).”

The SHR strain is a model for essential hypertension in humans because both the rodent and many humans with hypertension also develop a variety of other metabolic complications when high blood pressure strikes.

In the circulation of SHR rodents, Schmid-Schönbein and DeLano found significant levels of proteases, which are enzymes that break down proteins. Natural enzyme inhibitors found in normal healthy rats did not lower the level of protease activity in the SHR strain to normal levels.

“We were looking for a common cause of diverse but concurrent metabolic problems and we were testing our theory that enhanced proteolytic activity in the circulation may be the root cause,” said Schmid-Schönbein. “In the hypertensive rat we studied, enzymes cleave extracellular portions of several protein receptors, such as the insulin receptor, so that insulin can no longer bind and facilitate normal metabolism of glucose.”

Under normal conditions, the pancreas releases insulin in the bloodstream. The molecule then binds to insulin receptors on the cell-surface membrane, which signals the cells to absorb glucose, a main source of cellular energy. However, when a cell loses the binding site for insulin on the insulin receptors, it becomes “resistant,” or unresponsive to insulin and no longer absorbs glucose in healthy amounts on cue, which is the problem in type 2 diabetes.

The researchers showed that the SHR animals have protease activity in their circulation that cleaves more than just insulin receptors. In these animals, proteases also cleave significant numbers of CD18, an important binding receptor on the surface of infection-fighting leukocytes. CD18 gives these cells the ability to adhere to the walls of blood vessels as a way to home in on infections. With the loss of CD18 receptors, leukocytes of the SHR animals are unable to bind to the wall of blood vessels, resulting in a compromised immune system.

“These results point to a single mechanism that explains multiple and diverse cell dysfunctions encountered in hypertensive rats, and they also suggest that a similar mechanism may be operating in humans suffering simultaneously from hypertension, diabetes, and other metabolic conditions,” said Schmid-Schönbein.

The team went on to test whether administration of a protease-blocking drug could reverse the multiple metabolic complications in the rat strain. They administered doxycycline, a seemingly unlikely candidate to have such a beneficial effect. Infectious disease specialists often prescribe doxycycline, an antibiotic, to counter bacterial infections. However, in laboratory tests doxycycline also blocks the activity of certain proteases in the SHR strain of rat.

The researchers found that protein receptors on the surface of SHR cells become clipped off as the animals develop hypertension. They used a novel visualization technique to show that after several weeks of ingesting doxycycline in their drinking water, the SHR rats developed cells that again bristled with normal CD18 and insulin receptors. The animals’ metabolic conditions simultaneously improved; blood pressure normalized and symptoms of immune suppression disappeared.

“These studies indicate the first time that hypertension and cell dysfunctions associated with the metabolic syndrome may be part of an enzymatic auto-digestion process in which proteases in our body become uncontrolled and break down proteins,” Schmid-Schönbein said. “Our observations provide a conceptual framework in which we can start to understand how diverse complications in the metabolic syndrome arise.”

Schmid-Schönbein said his findings will likely spark follow-up studies of this mechanism in humans.

“Even if future studies only support the clear linkage of hypertension to insulin receptor cleavage in the current study of SHRs, this observation should lead to many studies of how these two problems perhaps interact,” wrote Bohlen in the Hypertension editorial. “To what extent this interaction is part of the cause or consequences of mechanisms associated with hypertension will remain controversial for some time to come. However, it is tempting to speculate that treatment of hypertension may be inadvertently improving insulin sensitivity and likely many other abnormalities associated with cell surface receptors that have been unknowingly damaged by protease activation associated with elevated blood pressure.”

Weight loss better than insulin therapy in type 2 Diabetes Mellitus

Tue, 11 Mar 2008 15:28:05 PST

( from http://www.rxpgnews.com ) Weight-loss and major lifestyle changes may be more effective than intensive insulin therapy for overweight patients with poorly controlled, insulin-resistant type 2 diabetes, according to a diabetes researcher at UT Southwestern Medical Center.

The National Heart, Lung, and Blood Institute of the National Institutes of Health recently halted part of an ongoing clinical trial on diabetes and heart disease after more than 250 people died while receiving intense treatment to drive their blood glucose levels below current clinical guidelines.

The evidence is compelling that when insulin levels are high, certain tissues are overloaded with fatty molecules, which leads to insulin resistance. And yet, the high blood glucose levels of many obese patients with insulin-resistant type 2 diabetes are being treated with increasing amounts of insulin in an attempt to overpower that resistance. While high doses of insulin may lower glucose levels, it will also increase the fatty molecules and may cause organ damage.

In a commentary in the March 12 issue of The Journal of the American Medical Association, Dr. Roger Unger, professor of internal medicine, wrote about the recent findings of his own and other labs that link insulin resistance to excess accumulation of fatty molecules in liver and muscle.

Dr. Unger, who has investigated diabetes, obesity and insulin resistance for more than 50 years said intensive insulin therapy is contraindicated for obese patients with insulin-resistant type 2 diabetes because it increases the fatty acids that cause diabetes. Instead, the most rational therapy eliminates excess calories, thereby reducing the amount of insulin in the blood and the synthesis of the fatty acids stimulated by the high insulin. Giving more insulin simply increases body fat.

“Evolution was unprepared for the change in the American diet to processed fast food and drive-through lanes,” he said. “There’s no way that our genes could evolve to gird themselves against the superabundance of very, very high-calorie foods that have flooded the U.S.”

Before the discovery of insulin, starvation was the only treatment for diabetes, said Dr. Unger, who is a member of the National Academy of Sciences.

“Today there are many treatment options, including bariatric surgery, if necessary, to lower the fat content in the body before you start giving insulin,” he said. “The fat is causing insulin resistance and killing the insulin-producing beta cells in the pancreas — that is what is causing type 2 diabetes.”

Giving more insulin simply channels the glucose into fat production. There is now a spectrum of therapies that improve diabetes by correcting the insulin resistance by reducing the body fat. Insulin treatment would be indicated only if all these fail.

Dr. Unger said insulin should be given to patients with insulin deficiency, but not if the insulin levels are already very high but ineffective. “Giving more insulin to an insulin-resistant patient is akin to raising the blood pressure of a patient with high blood pressure to overcome resistance to blood flow. Instead, you would try to reduce the resistance,” he said.

In the commentary, Dr. Unger said the increase in the number of patients with insulin-resistant type 2 diabetes can be traced to the epidemic of obesity that began in the U.S. after World War II, when food preparation was moved from the family kitchen to factories and companies that produce high-fat, calorie-dense foods, leading both men and women to consume substantially more calories on a daily basis. In addition, technological advancements such as televisions, computers and automobiles reduced the number of calories burned per day.

Type 2 diabetes occurs when the body is unable to make enough of the hormone insulin to compensate for insulin resistance. The condition affects between 18 million and 20 million people in the U.S.

Factors that increase the risk of type 2 diabetes include obesity, age and lack of exercise. Over a period of years, high blood sugar damages nerves and blood vessels, leading to complications such as heart disease, stroke, blindness and kidney disease.

Personal counseling helps in maintaining weight loss

Tue, 11 Mar 2008 15:16:58 PST

( from http://www.rxpgnews.com ) People who shed weight and want to keep it off might benefit from monthly personal contact interventions, researchers reported at the American Heart Association’s Conference on Nutrition, Physical Activity and Metabolism.

Results of the study will also be simultaneously published in the Journal of the American Medical Association.

In a test of three ways that might help people maintain weight loss, those who received monthly personal counseling were best at keeping off unwanted pounds. Overall, 42 percent of the study members maintained at least a 4-kilogram (9-pound) weight loss for 30 months.

“We know how to help people lose weight in a healthy way, but we know very little about how to help them to keep the weight off,” said Laura P. Svetkey, M.D, lead author of the study and professor of medicine at Duke University Medical Center in Durham, N.C. “This study is the longest and largest to test strategies for long-term weight loss maintenance, and it suggests that long-term weight control is an achievable goal.

“The United States is in the midst of an obesity epidemic, one that portends serious future health consequences. Overweight and obesity are the leading cause of high blood pressure, diabetes and abnormal cholesterol, which are leading causes of cardiovascular disease, which is, in turn, the leading cause of death in this country,” Svetkey said. “So if we really want to get to the root causes of these disorders, we need to address the obesity epidemic.”

Despite the importance of obesity control, few studies have tested strategies to maintain weight loss over long periods. Svetkey and her colleagues enrolled 1,685 participants in the two-phase Weight Loss Maintenance trial, which was conducted at four clinical centers in the United States.

Phase I consisted of 20 weekly group sessions of 18-25 participants held over six months, during which trained counselors emphasized three key elements to weight loss — consuming fewer calories, increasing moderate physical activity, and eating a healthy diet.

Researchers recommended DASH (Dietary Approaches to Stop Hypertension), a diet rich in fruits, vegetables, whole-grain and high fiber foods, that uses low-fat and fat-free dairy products and is low in total and saturated fat and sodium. DASH lowers blood pressure and cholesterol even without weight loss.

Counselors helped participants use tools like self-monitoring and goal-setting, and helped them remember why they wanted to lose weight in the first place. The group sessions also provided study members with social support from other participants.

At the end of Phase I, 61 percent of the participants in the trial were eligible for Phase II, which lasted for 30 months, because they had lost at least nine pounds and as much as 66 pounds.

Thirty-eight percent of people in Phase II were African-American and 37 percent were male. “This is important because men are often underrepresented in weight loss studies, and obesity disproportionately affects African Americans,” Svetkey said.

Researchers randomly assigned the volunteers to one of three groups:

Personal contact (PC) — Participants talked with an interventionist (monthly, nine times by telephone and three times face-to-face each year) who provided personal counseling and encouragement.
Interactive technology (IT) — Study members had access to an interactive Web site on which they could record and track their exercise and calorie intake; set goals and monitor their progress toward them; and communicate with others in the IT group.
Self-directed (SD) — Participants were urged to maintain their weight loss and then sent off without further intervention.
Results from the trial after 30 months included:

Overall, 71 percent weighed less than when they began Phase I. The difference in the percentage of each group that weighed less was statistically significant — PC group (77 percent); IT group (69 percent) and SD group (67 percent).
Thirty-seven percent of enrollees weighed at least 5 percent below their beginning weight. Again, the PC participants (42 percent) significantly out-performed those in the SD (34 percent) and IT (29 percent) groups.
Among all study members, 32 percent weighed no more than 3 percent above their weight at randomization. However, differences between the three groups — SD (29 percent), IT (29 percent) and PC (36 percent) — were not significantly different statistically.
Although at 24 months the average weight regained by the IT group was less than that of the SD arm, researchers found no difference between the two at 30 months.
“The effects we observed were modest,” Svetkey said. “The personal contact group regained about 3.3 pounds less than the self-directed group.”

Even a small weight loss can have potential health benefits, she noted.

“Each pound of weight loss can lower blood pressure by as much as a millimeter of mercury, and the more weight you lose, the bigger the blood pressure effect,” Svetkey said. “Each pound of weight loss is estimated to lower the risk of developing diabetes by 8 percent, which is quite impressive.

“Clearly more research is needed to refine these maintenance interventions to make them more effective, but this study is an important step in the right direction.”

Type 2 muscle important in body metabolism and obesity

Tue, 05 Feb 2008 23:07:33 PST

( from http://www.rxpgnews.com ) When it comes to losing weight, pumping iron may be just as important as running on the treadmill, suggests a new study in the February issue of Cell Metabolism, a publication of Cell Press.

Researchers used a genetic trick in obese mice that caused the mice’s muscles to bulk up as though they had been lifting weights. The researchers found that the “genetically reprogrammed” mice lost fat and showed other signs of metabolic improvement throughout the body. What’s more, those benefits were seen even though the mice continued eating a diet high in both fat and sugar and didn’t increase their physical activity at all.

“We’ve shown that type II muscle does more than allow you to pick up heavy objects,” said Kenneth Walsh of Boston University School of Medicine. “It is also important in controlling whole-body metabolism.”

The type II, or fast, muscle fibers found plentifully in body builders are well suited to dealing with abrupt and heavy loads. On the other hand, the muscles of long-distance runners are rich in type I, or slow, fibers that can endure lesser loads over longer periods of time. Earlier studies focused primarily on the importance of type I muscle, with its abundance of energy-burning mitochondria, for regulating metabolism, Walsh said. Indeed, those studies have indicated that an increase in “energy burn” in muscle can protect against weight gain and metabolic dysfunction.

“Resistance training builds the white meat,” Walsh said, referring to the relatively mitochondria-poor type II muscle. “There is some evidence it’s good for you, but it’s not immediately clear why. Now, we’ve provided a scientific rationale.”

Walsh’s group developed mice in which they could turn type II muscle growth on or off by flipping a genetic switch specifically in skeletal muscle. The gene they manipulated, known as Akt1, is preferentially activated in skeletal muscle in response to resistance training, but not endurance training, the researchers knew.

Rather than becoming strong and fat “sumo mice” as some of the researchers had expected, the modified mice gained type II muscle and strength while they lost fat. The mice also showed a resolution of hepatic steatosis, otherwise known as fatty liver, and improvements in a variety of other metabolic parameters. The Akt1-driven growth of skeletal muscle counteracted the usual effects of a high-fat, high-sucrose diet on patterns of gene activity in the liver and increased the breakdown of fatty acids there, the researchers showed.

“These findings indicate that type II muscle has a previously unappreciated role in regulating whole-body metabolism through its ability to alter the metabolic properties of remote tissues,” the researchers concluded. “These data also suggest that strength training, in addition to the widely prescribed therapy of endurance training, may be of particular benefit to overweight individuals.”

“The work of [Walsh and his colleagues] reveals the intricate interplay between diet, energy balance, and the function/morphology of diverse tissue systems such as skeletal muscle and liver,” said Brooke Harrison and Leslie Leinwand of the University of Colorado at Boulder in a commentary. “These findings indicate that interventions designed to increase skeletal muscle mass in at-risk human populations may prove to be critical weapons in the fight against obesity and obesity-related comorbidities including diabetes, heart disease, stroke, hypertension, and cancer.”

A Predisposition to Obesity

Tue, 05 Feb 2008 15:11:27 PST

( from http://www.rxpgnews.com ) A predisposition for obesity might be wired into the brain from the start, suggests a new study of rats in the February issue of Cell Metabolism, a publication of Cell Press.

Rats selectively bred to be prone to obesity show abnormalities in a part of the brain critical for appetite control, the researchers found. Specifically, the researchers show that the obese rats harbor defects in neurons of the arcuate nucleus (ARH) of the hypothalamus, which leaves their brains less responsive to the hunger-suppressing hormone leptin.

“The neurodevelopmental differences in these animals can be seen as early as the first week,” said Sebastien Bouret of the University of Southern California. “The results show that obesity can be wired into the brain from early life. The three-million-dollar question now is how to get around this problem.”

It is increasingly accepted that obesity results from a combination of genetic and environmental factors, the researchers said. Rodent models of obesity can provide valuable insights into the biological processes underlying the development of obesity in humans. The “diet-induced obese” (DIO) rats used in the current study are particularly suited to the task, according to Bouret, because their tendency to become overweight shares several features with human obesity, including the contribution of many genes.

Previous studies had suggested that the brains of DIO rats are insensitive to leptin, the researchers added. Circulating leptin, produced by fat tissue, acts as a signal to the brain about the body’s energy status. Leptin is also critical for the initial development of ARH neurons.

In the new study, the researchers examined the obesity-prone rats for signs of abnormal brain development. They found that the animals’ brains had fewer neural projections from the ARH, a deficiency that persisted into adulthood. Those projections are needed to relay the leptin signal received by the ARH to other parts of the hypothalamus, Bouret said.

The researchers found further evidence that those changes in brain wiring stem from a reduced responsiveness of the brain to leptin’s action during development.

“It seems [in the case of these rats] that appetite and obesity are built into the brain,” Bouret said. While their condition might be ameliorated by exercising and eating right, he added, the findings suggest that the propensity to gain weight can’t be reversed.

But there is hope yet. It’s possible that treatments delivered during a critical early period of development might be capable of rewiring the brain, Bouret said.

Obesity in mothers responsible for obese offspring

Thu, 03 Jan 2008 14:59:06 PST

( from http://www.rxpgnews.com ) The number of overweight and obese Americans continues to grow rapidly. Today, 50 percent of adults are overweight and up to 20 percent are obese. While the number of overweight/obese children is at an all time high, the steady increase of overweight infants -- individuals under 11 months old -- is alarming.

Research studies have found that pregnant women who are overweight/obese are more likely to give birth to heavier babies, and the risk of overweight children becoming obese adults is nearly nine times greater than for children who are not overweight. Studies also show that greater body-weight at birth and weight gain early in life increases the risk of becoming overweight or obese as an adult. Inheritance studies show that a child's body mass index (BMI) correlates more closely with the mother's BMI than with it's father's, suggesting that an interaction of both genetic and intrauterine influences, may contribute to later-life obesity risk in the offspring.

Armed with these and other data, a team of researchers from the USDA-Arkansas Children's Nutrition Center has examined whether the subtle effects of fetal exposure to the mother's obesity can have a latent effect on the offspring. In a new report, investigators studied whether fetal exposure to gestational obesity leads to a self-reinforcing viscious cycle of excessive weight gain and body fat which passes from mother to child. The results of the new study suggest they do.

The Study

The study is entitled, "Maternal Obesity at Conception Programs Obesity in the Offspring." It was conducted by the research team of Kartik Shankar, Amanda Harrell, Xiaoli Liu, Janet M. Gilchrist, Martin J.J. Ronis and Thomas M. Badger, all of the Arkansas Children's Nutrition Center, Little Rock, AR. Their findings appear in the online edition of the American Journal of Physiology -- Regulatory, Integrative and Comparative Physiology (doi:10.1152/ajpregu.00316.2007). The journal is one of 11 published each month by the American Physiological Society (APS; http://www.the-aps.org/).

To test the theory that obesity in adulthood may be subject to programming during fetal development, the researchers developed an overfeeding model which was used in rats. The model allowed the investigators to replicate many of the metabolic and hormonal features of overweight human individuals. They were also able to exclude parental genetic influences, match gestational weight gain, limit the exposure of maternal obesity in utero, and control lactation efficiency, all of which can be difficult confounding variables in studies with human subjects.

Summary of Methodology

Virgin female rats were fed liquid diets via enteral nutrition at one of two caloric levels: (1) the caloric level recommended by the National Research Council (187 kcal/kg3/4/day) or (2) a level of 15 percent overfeeding (220 kcal/kg3/4/day). In the preliminary experiments, the rats consuming the normal caloric intake had weight gains similar to controls while those being fed the obesegenic diet had become substantially overweight. Body weights were monitored three times a week and body composition was analyzed non-invasively on a regular basis.

To examine the long-term gestational effects of maternal obesity on the offspring, lean (n=7) and obese (n=15) rats were allowed to mate with normal (lean) male rats for a period of one week. Following mating, all female rats (lean and obese) received respective diets at 15 percent excess calories per day in order to ensure adequate caloric intake for pregnancy. Maternal body weights were monitored three times a week and all rats gave birth naturally. Offspring born to lean or obese rats were raised by surrogates who were fed regular rodent diets to ascertain the pups' obesity exposure was limited only during gestation.

The male offspring from each group were weaned from the surrogate mother at 21 days after birth and fed (by giving unlimited access to) either a normal diet or a high-fat diet. The pups' body weight, body composition and other factors were analyzed for 130 days. At day 130 additional samples were taken and analyzed, to include organ weights, glucose and triglyceride levels, fat cell size, body composition and hormones.

Key Findings

The researchers found the following:

at birth, the weight of the offspring from both groups was similar. The number and size of pups and the ratio of males to females did not differ significantly.

the amount of calories the pups consumed (relative to their body-weight) at the 60- and 120-day mark suggested that both groups consumed the same amount of calories, indicating no effect of maternal obesity on the offspring's food intake.

when both the lean and obese offspring were fed a control diet, their body weights remained similar. However, when both groups were fed a high-fat diet, the obese offspring gained remarkably more weight, suggesting that exposure to maternal obesity led to programming of increased susceptibility to obesity in the offspring, which was revealed following an obesegenic challenge despite a normal birth weight.

when both groups were fed a control diet, obese offspring had a ~ 1.6 times greater fat ratio compared to their lean offspring counterparts. Further, obese offspring fed a high-fat diet had a 26 percent greater percent fat ratio and a 60 percent increase in subcutaneous fat mass vs. lean offspring.

high fat feeding significantly increased serum glucose, triglyceride, insulin and leptin levels in both groups. Strikingly, the serum insulin and leptin levels increased by 2.2 and 2.3 fold in obese offspring compared to lean offspring fed the same diet.

Conclusions

These findings add to the existing body of evidence showing that both maternal obesity and genetic background influence offspring's susceptibility to obesity. It goes further, to highlight the role of post-natal obesegenic diet as a determinant in revealing subtle programming imposed by maternal obesity. The results also demonstrate that high levels of adiposity (body fat) occur in the offspring of obese mothers despite consuming similar calories as their lean-offspring counterparts and that offspring obesity is associated with insulin resistance.

The "programming" of susceptibility to obesity occurs in the absence of changes in birth weights and other fetal outcomes.

According to Dr. Kartik Shankar of the Arkansas Children's Nutrition Center, "The mother's body composition at conception has important implications for the metabolism and risk of obesity in the offspring in later years. Not only do these findings help us appreciate the reasons for the rapid rise in obesity, this novel model will allow us to understand the underlying mechanisms and should provide fertile opportunity for translational type research."

Low-carb diets' effects linked to increased levels of FGF21

Wed, 06 Jun 2007 16:01:00 PST

( from http://www.rxpgnews.com ) The benefits sometimes seen in those on a low-carbohydrate, high-fat diet may depend on increased levels of a newly identified starvation hormone produced by the liver, according to a report in the June issue of the journal Cell Metabolism, published by Cell Press. Two studies in the issue show that the hormone plays a critical role in the metabolic shift seen in animals after a period of fasting and in those fed an Atkins-like diet. That shift is characterized by an increased reliance on fat stores as an alternative source of fuel when glucose, the body?s primary energy source, plummets.

A team led by Eleftheria Maratos-Flier of Harvard University reports evidence that increased blood levels of liver-derived fibroblast growth factor 21 (FGF21) are required for fasted mice and mice on a carbohydrate-restricted diet to switch gears and begin burning fat. Likewise, an accompanying study led by Steven Kliewer of the University of Texas Southwestern Medical Center found that FGF21 mobilizes fat in food-restricted animals and those with chronically elevated concentrations of the liver hormone. Kliewer?s team further showed that the hormone contributes to energy-conserving behavioral changes as animals ride out food shortages.

What?s really exciting is that mice with excess FGF21?even when they are fed?look like they are fasted, Kliewer said. It?s startling that you can give one hormone and flip the whole metabolic profile.

We think these findings would increase the desirability of a drug that [might work through this mechanism] to increase fat oxidation in the liver, added Maratos-Flier, noting that the rise in obesity has contributed to a growing epidemic of nonalcoholic fatty liver disease. Although the physiology remained uncertain, pharmacological studies of mice and diabetic monkeys had previously shown promise for FGF21 therapy as a means to lower blood sugar and lipids and stave off weight gain.

Mammals survive periods of nutrient deprivation by shifting from carbohydrates to so-called ketone bodies as a primary fuel source. Ketone bodies are produced from fatty acids transferred from storage in fat tissue to the liver when carbohydrates are scarce.During prolonged fasts, ketone bodies can provide nearly half of baseline energy requirements and up to 70% of the energy required by the brain.

Earlier studies also showed that feeding rodents a high-fat, low-carbohydrate (ketogenic) diet induces lipid oxidation associated with weight loss, according to Maratos-Flier. Yet the underlying mechanism responsible for the profound physiological changes that the diets induced wasn?t fully understood.

In the new study, Maratos-Flier?s team examined changes in gene activity occurring in mice fed a high-fat, low-carb diet for 30 days. Their comprehensive genetic screen of the animals, which lost weight on the special diet, turned up FGF21.

We saw a dramatic increase in FGF21 in the livers of the mice [on the diet], she said. We thought, ?Maybe there is something to this.?

Through further experimentation, the researchers found that liver and circulating levels of FGF21 increase in mice in response to both a low-carb, high-fat diet and fasting. Moreover, the hormone declined rapidly when fasted animals were fed again. In mice unable to produce FGF21 in their livers, the special diet resulted only in fatty liver, high blood lipids, and reduced blood ketones, due at least in part to altered expression of key genes governing lipid and ketone metabolism.

Meanwhile, Kliewer?s group identified the FGF21 endocrine hormone as a mediator of peroxisome proliferator-activated receptor (PPAR). Scientists have known that PPARcontrols fats? use as an energy source during starvation. In addition, some drugs that lower bad cholesterol work by targeting PPAR

Kliewer?s group showed that FGF21 is induced directly by PPAR in liver in response to fasting in mice. FGF21 in turn stimulates lipid breakdown in white adipose tissue and ketone body production in the liver. They unexpectedly also found that FGF21 led the animals to reduce their physical activity and made them more sensitive to entering torpor, a short-term, hibernation-like state.

In addition to altering their fuel sources, many small mammals conserve energy when food is scarce by undergoing periodic bouts of torpor, Kliewer explained.

When you step back, the whole thing makes sense, he said. During fasting, the liver hormone communicates with adipose tissue to send fat to the liver. It turns on the metabolism of fat into ketone bodies?and at the same time, it sensitizes the animals to going into torpor to conserve energy. It?s clear that FGF21 is a principal component of the fasting or starvation response.

The two studies together lead to an obvious possibility that FGF21 accounts for the proposed positive effect of the Atkins diet?including weight loss and an increase in ?good? cholesterol, Kliewer continued.

The degree to which the physiological effects of a ketogenic diet in humans mimic those seen in mice remains to be determined, Maratos-Flier added. She intends to examine FGF21 levels in humans after a few days on the Atkins diet, she said.

Either way, such low-carb, high-fat diets aren?t likely to work for everyone.

It may be that some people are more likely to turn on FGF21 than others, Maratos-Flier said. In obese individuals, for example, high insulin levels may interfere with the liver hormone, she said.

Study identifies new regulator of fat metabolism

Wed, 06 Jun 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Over the past several years, animal studies have shown that high-fat, low-carbohydrate ?ketogenic? diets cause demonstrable changes in metabolism and subsequent weight loss. Now, researchers at Beth Israel Deaconess Medical Center (BIDMC) have identified a key mechanism behind this turn of events. Their findings, which appear in the June 2007 issue of Cell Metabolism, demonstrate that a liver hormone known as FGF21 is required to oxidize fatty acids ? and thereby burn calories.

When the diet is extremely low in starches and sugars, blood sugar levels drop substantially so that muscle and brain have to turn to alternative fuels,? explains senior author Eleftheria Maratos-Flier, MD, an investigator in the Department of Endocrinology, Diabetes and Metabolism at BIDMC and Associate Professor of Medicine at Harvard Medical School. ?Consequently, fatty acids are broken down in the liver and converted to ketones, which then serve as a major fuel source.?

Known as ketosis, this metabolic state is characterized by extremely low insulin levels, as would occur during periods of fasting or starvation or while consuming a low-carb diet, such as the popular Atkins diet model.

For the past several years, Maratos-Flier?s laboratory has been studying the physiologic states of animals consuming various types of diets -- including standard ?animal chow? diets and diets moderately high in both fats and carbohydrates, as well as ketogenic diets. And she has found through her experiments that even though mice are fed exactly the same number of calories, the composition of the calories causes them to gain weight in different ways.

?The differences in weight gain reflect differences in metabolic rates,? she explains. ?These, in turn, result in hormonal changes that lead to different disposition of the calories.?

In this latest paper, Maratos-Flier and colleagues studied mice that had been fed a ketogenic diet high in both saturated fat and unsaturated fat and practically devoid of carbohydrates.

?Despite the high fat content of this diet, the study animals maintained normal levels of circulating lipids,? she explains. ?We wanted to learn what factors might be responsible for creating this state in which consumed calories were being burned off in the liver rather than being stored as fat.?

Because the physiologic changes in the animals didn?t appear to be explained by typical hormonal regulators ? neurotransmitters that normally regulate appetite -- the researchers set out to identify which genes were unique to this ketogenic phenotype, exploring the possibility that hepatocytes were playing an active role in the process.

And, using micoarray gene analysis, they discovered that their hunch was correct: FGF21, a liver-derived fibroblast growth factor gene, was significantly increased in the mice that had been fed ketogenic diets.

?FGF21 had previously been identified as a potential metabolic regulator by scientists at Eli Lilly, who showed that transgenic mice that overexpressed FGF21 were protected from diet-induced obesity, had smaller fat cells and had more brown adipose tissue,?says Maratos-Flier. ?But little was actually known about FGF21?s physiologic roles. Working with Jeffrey Flier?s lab, we were able to show that FGF21 is essential for fatty acid oxidation.?

Furthermore, she explains, when FGF21 was inhibited, the mice developed a massive accumulation of fat in the liver and an extreme increase in circulating lipids.

A second study by Maratos-Flier and colleagues published in the June 2007 issue of the American Journal of Physiology further elucidates the unique metabolic changes that occur with the consumption of a ketogenic diet.

?Although the purpose of both of these studies was to glean insights into metabolic physiology, our findings suggest that increased levels of FGF21 may be a potential mechanism behind low-carbohydrate diets? beneficial properties when it comes to lipid metabolism,? says Maratos-Flier. ?Diets that limit carbohydrates and eliminate transfats, and at the same time emphasize fiber and good fats, appear to be healthiest, especially among individuals who are predisposed to developing diabetes.?

Study of protein folds offers insight into metabolic evolution

Sun, 20 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Illinois have constructed the first global family tree of metabolic protein architecture. Their approach offers a new window on the evolutionary history of metabolism.

The study appears this week in the online edition of the Proceedings of the National Academy of Sciences.

Their work relies on established techniques of phylogenetic analysis developed in the past decade to plot the evolution of genes and organisms but which have never before been used to work out the evolutionary history of protein architecture across biological networks.

We are interested in how structure evolves, not how organisms evolve, said professor of crop sciences Gustavo Caetano-Anoll's, principal researcher on the study, which was co-written by graduate student Hee Shin Kim and emeritus professor of cell and developmental biology Jay E. Mittenthal. We are using the techniques of phylogenetic analysis that systematicists used to build the tree of life, and we are applying it to a biochemical problem, a systems biology problem.

To get at the roots of protein evolution, the researchers examined metabolic proteins at the level of their component structures: easily recognizable folds in the proteins that have known enzymatic activities. These protein domains catalyze a range of functions, breaking down or combining metabolites, small molecules that include the building blocks of all life.

Their findings relied on a fundamental assumption: that the most widely utilized protein folds (they looked at proteins in more than 200 species) were also the most ancient.

Protein architecture has preserved ancient structural designs as fossils of ancient biochemistries, the authors wrote.

The team used data from two international compilations of genetic and proteomic information: the metabolic pathways database of the Kyoto Encyclopedia of Genes and Genomes, and the Structural Classification of Proteins database. They combined these two data sets with phylogenetic reconstructions, or family trees, of protein fold architectures in metabolism.

Obesity increases risk of injury on the job

Tue, 15 May 2007 18:58:11 PST

( from http://www.rxpgnews.com ) Having a body mass index (BMI) in the overweight or obese range increases the risk of traumatic workplace injury, according to researchers at the Johns Hopkins Bloomberg School of Public Healthâs Center for Injury Research and Policy. Employer-sponsored weight loss and maintenance programs should be considered as part of a well-rounded workplace safety plan. The study was Advance Access published on May 7, 2007, by the American Journal of Epidemiology.

BMI is a measure of body fat based on an adultâs height and weight. It is used to screen for weight categories that may lead to health problems. According to the Centers for Disease Control and Prevention, a BMI below 18.5 is considered underweight, 18.5â24.9 is normal; 25â29.9 is overweight and over 30 is obese.

âClearly, limited resources for workplace injury prevention and control should target the most prominent and modifiable risk factors, but we cannot neglect the fact that our study and other recently published studies support an association between BMI and the risk, distribution and prevalence of workplace injury,â said Keshia M. Pollack, PhD, MPH, lead author of the study and an assistant professor in the Bloomberg School of Public Healthâs Department of Health Policy and Management.

The researchers used medical and injury surveillance data on hourly workers employed in eight plants of the same aluminum manufacturer to determine whether increased BMI was a risk factor for workplace injury. The plants were scattered across the United States. BMI was calculated using National Institutes of Health criteria. Employees were grouped into five categories: underweight, normal, overweight, obesity levels I and II and obesity level III.

Of the 7,690 workers included in the study, 29 percent were injured at least once between January 2, 2002, and December 31, 2004. Approximately 85 percent of the injured workers were classified as overweight or obese. More than 28 percent of injuries occurred among employees classified as overweight, 30 percent in the obese I and II category and almost 34 percent in the obese III category.

The severely obese group who had a BMI of greater than 40 also had the most injuries to the hand/wrist/finger (22 percent) when compared to the same injuries in the other weight categories. Almost 10 percent of all injuries in the obese III group were to the leg/knee, compared to 7 percent of workers classified as overweight, which was the next highest injury rate.

âWe know that obesity prevention policies and programs in the workplace are important simply because of likely improvements in employee health,â said Pollack, the Leon S. Robertson Faculty Development Chair in Injury Prevention. âWhat we do not know is if obesity prevention in the workplace will also have the added benefit of improving injury rates and reducing lost work time. Evaluations of worksite health promotion and obesity prevention efforts should measure changes not only in employee health, but also traumatic injury.â

The researchers say that more work will be needed to test the effectiveness for reducing weight among hourly (non-office) employees who face a number of barriers to participating in worksite physical activity programs, such as the need to remove protective clothing for midday exercise and a lack of time because of additional employment or home responsibilities.

Major genetic study identifies gene for obesity

Sat, 14 Apr 2007 03:35:51 PST

( from http://www.rxpgnews.com ) Scientists have identified the most clear genetic link yet to obesity in the general population as part of a major study of diseases funded by the Wellcome Trust, the UK's largest medical research charity. People with two copies of a particular gene variant have a 70 per cent higher risk of being obese than those with no copies.

Obesity is a major cause of disease, associated with an increased risk of type 2 diabetes, heart disease and cancer. It is typically measured using body mass index (BMI). As a result of reduced physical activity and increased food consumption, the prevalence of obesity is increasing worldwide. According to the 2001 Health Survey for England, over a fifth of males and a similar proportion of females aged 16 and over in England were classified as obese. Half of men and a third of women were classified as overweight.

Scientists from the Peninsula Medical School, Exeter, and the University of Oxford first identified a genetic link to obesity through a genome-wide study of 2,000 people with type 2 diabetes and 3,000 controls. This study was part of the Wellcome Trust Case Control Consortium, one of the biggest projects ever undertaken to identify the genetic variations that may predispose people to or protect them from major diseases. Through this genome-wide study, the researchers identified a strong association between an increase in BMI and a variation, or "allele", of the gene FTO. Their findings are published online today in the journal Science.

The researchers then tested a further 37,000 samples for this gene from Bristol, Dundee and Exeter as well as a number of other regions in the UK and Finland. Bristol Universityâs ALSPAC study (also known as Children of the 90s), which has followed the development of 14,000 children since before birth, made a significant contribution to this work.

The study found that people carrying one copy of the FTO allele have a 30 per cent increased risk of being obese compared to a person with no copies. However, a person carrying two copies of the allele has a 70 per cent increased risk of being obese, being on average 3kg heavier than a similar person with no copies. Amongst white Europeans, approximately one in six people carry both copies of the allele.

"As a nation, we are eating more but doing less exercise, and so the average weight is increasing, but within the population some people seem to put on more weight than others," explains Professor Andrew Hattersley from the Peninsula Medical School. "Our findings suggest a possible answer to someone who might ask 'I eat the same and do as much exercise as my friend next door, so why am I fatter?' There is clearly a component to obesity that is genetic."

The researchers currently do not know why people with copies of the FTO allele have an increased BMI and rates of obesity.

"Even though we have yet to fully understand the role played by the FTO gene in obesity, our findings are a source of great excitement," says Professor Mark McCarthy from the University of Oxford. "By identifying this genetic link, it should be possible to improve our understanding of why some people are more obese, with all the associated implications such as increased risk of diabetes and heart disease. New scientific insights will hopefully pave the way for us to explore novel ways of treating this condition."

The findings were welcomed by Dr Mark Walport, Director of the Wellcome Trust.

"This is an exciting piece of work that illustrates why it was so important to sequence the human genome," says Dr Walport. "Obesity is one of the most challenging problems for public health in the UK. The discovery of a gene that influences the development of obesity in the general population provides a new tool for understanding how some people appear to gain weight more easily than others. This discovery, along with further results expected from the Wellcome Trust Case Control Consortium later this year, will open up a wealth of new avenues to understand and treat common diseases."

The FTO gene was first discovered whilst studying the DNA of a cohort of patients with type 2 diabetes. The risk of developing type 2 diabetes increases significantly for obese people. Through its effect on BMI, having one copy of the FTO allele increases the risk of developing type 2 diabetes by 25 per cent, having two by 50 per cent.

"We welcome this result, which holds promise for tackling rising levels of obesity and the associated risk of developing type 2 diabetes," says Professor Simon Howell, Chair of Diabetes UK, which funded the original collection of samples from people with diabetes. "The discovery has been possible not only because of exemplary team work of scientists from a large number of institutions but also because of the cooperation of the 5,000 diabetes patients and 37,000 people without diabetes who gave blood samples for the study."

Incidence of Fatty Liver Disease rises as obesity in children increases

Thu, 15 Mar 2007 06:11:55 PST

( from http://www.rxpgnews.com ) Indiana University School of Medicine researchers are taking a closer look at a disease whose incidence is rising as obesity in children increases. Non-Alcoholic Steatohepatitis, more popularly known as Fatty Liver Disease, occurs in approximately 15% of obese children. Fatty Liver Disease, in which fat accumulates in the liver, while not life threatening in children, can lead to cirrhosis (scarring) of the liver, sometimes requiring transplantation by adulthood.

"Until now the only treatment for Fatty Liver Disease has been to offer diet and exercise counseling, but this is often not effective. As part of a national multicenter research network, we are now looking at Vitamin E and at metformin, a drug used to treat Type II diabetes, as possible therapies" said Jean Molleston, M.D., clinical professor of pediatrics at IU School of Medicine and director of pediatric gastroenterology at Riley Hospital for Children. Dr. Molleston is the pediatric principal investigator for the IU School of Medicine site of TONIC, an eight-center Phase III study funded by the National Institute of Diabetes and Digestive and Kidney Disease, which is investigating treatment options for Fatty Liver Disease in 8 to 17 year olds and is the largest study of its type to date.

"We are seeing a growing number of young people with Fatty Liver Disease, and we need to tackle the disease before it becomes full blown in adulthood," said Dr. Molleston. "We routinely test children for conditions with much lower incidence such as scoliosis. Although we do not yet have formal guidelines for screening for Fatty Liver Disease, I personally think that all obese children should be screened for Fatty Liver Disease so we can intervene before it damages the liver."

A simple blood test to determine if liver enzyme levels are elevated alerts pediatricians that the child needs to be evaluated for Fatty Liver Disease.

Approximately a third of children and teens in the United States are overweight and 15% of children and teens are obese. Fatty Liver Disease may exist in 15% or more of obese children.

The American Liver Foundation estimates that 10-20% of Americans have Fatty Liver Disease.

ApoC1 linked with elevated BMI, obesity and Type 2 diabetes

Thu, 22 Feb 2007 07:46:37 PST

( from http://www.rxpgnews.com ) University of Minnesota researchers have discovered a variant of a common blood protein, apolipoprotein C1, in people of American Indian and Mexican ancestry that is linked to elevated body mass index (BMI), obesity and Type 2 diabetes.

The finding were published in the Feb. 20 online issue of the International Journal of Obesity.

Lead investigator Gary Nelsestuen, a professor in the College of Biological Sciences department of biochemistry, said the abnormal protein may promote metabolic efficiency and storage of body fat when food is abundant. This could have provided a survival advantage to American Indians in the past when food was scarce. The discovery can be used to identify those who are at risk for diabetes and to guide diet and lifestyle choices to prevent diabetes.

Apolipoprotein C1 is a component of high density lipoprotein (HDL) and low density lipoprotein (LDL). HDL cholesterol is often referred to as good cholesterol, while LDL is called bad cholesterol. The common form of C1 tends to be found in the high-density protein complexes (HDL) that ferry cholesterol to storage depots in the body and are linked to lower cardiovascular disease risk. But the variant form of C1 tends to become part of low density protein complexes (LDL), which transport cholesterol to arterial walls and are associated with higher cardiovascular disease risk. Thus, having the variant could tip the balance of cholesterol carriers and lead toward depletion of HDL-also a risk factor for heart disease. The variant differs from the normal protein by a single change in one of its 57 amino acids.

Among 1500 subjects from widely divergent genetic backgrounds, the variant was found in 35 of 228 persons with American Indian ancestry and in 10 of 84 persons with Mexican ancestry. The average body mass index (BMI) of persons with the variant protein was 9 percent higher and the diabetes rate 50 percent higher among study subjects and their parents. Parents were included because type 2 diabetes often doesn't appear until later in life.

This project has been a departure for Nelsestuen, who has made important discoveries related to blood coagulation proteins involved in bleeding disorders such as hemophilia and coagulation disorders such as sepsis and thrombosis. The university has licensed these proteins to three pharmaceutical companies who are developing them as therapeutic agents. Nelsestuen is recognized on the universitys Wall of Discovery for some of these achievements.

Nelsestuen used income from the blood coagulation protein licenses and his endowment from the Samuel Kirkwood Chair to support the research that led to finding the abnormal variant of C1 lipoprotein.

The funds were used to apply new proteomics technology to screen blood samples for proteins related to disease. This type of protein screening is often described as "discovery" research. In its purest form, proteomics discovery research looks for abnormal proteins in what seems like a random process.

"This type of research is often dismissed as a fishing expedition by funding agencies," Nelsestuen said. "But our finding shows the value of discovery research and of having unrestricted funds to pursue it."

Nelsestuens interest in education of minority graduate students provided many of the connections to the communities that became involved in this research. Former student Michael Martinez, helped establish a collaboration with Kenneth McMillan, medical director of the American Indian Community Development Corporation in Minneapolis, and Cristina Flood-Urdangarin of St. Marys Health Clinics in St. Paul.

Nelsestuens next steps will be to expand the study to the Turtle Mountain Indian Reservation in North Dakota and the Cheyenne River Indian Reservation in South Dakota.

"I hope that this discovery will ultimately lead to a Minnesota center for research on minority health issues that can deliver actual health benefits to these communities," Nelsestuen said.

Acquired obesity primarily relates to increases in lysophosphatidylcholines

Wed, 14 Feb 2007 10:15:34 PST

( from http://www.rxpgnews.com ) Obesity and its many related health hazards have become a serious and growing problem worldwide. While environmental and lifestyle factors play a key role in the development of obesity, genetic variation may determine an individual's susceptibility to weight gain and to the rise of obesity-related health risks. Obesity increases the risk of cardiovascular diseases and diabetes especially when the extra fat is accumulated to central and intra-abdominal depots and when obesity is accompanied by an atherogenic dyslipidemia.

A Finnish team from the Finnish Twin Cohort, Helsinki University Central Hospital, and VTT Technical Research Centre of Finland performed a metabolomic analysis of lipids in 14 monozygous twins highly discordant for obesity, and 10 control pairs concordant for weight. They found that acquired obesity, independent of genetic influences, primarily relates to increases in lysophosphatidylcholines, constituents of an atherogenic lipid profile and decreases in ether phospholipids, lipids with anti-oxidative properties.

The origin of obesity and related dyslipidemias is multifactorial, involving complex genetic and environmental networks. Not all obese individuals develop dyslipidemia and not all dyslipidemic patients are obese. Cross-sectional studies comparing lipid profiles in obese vs. non-obese humans do not permit unequivocal distinction between genetic versus environmental and life-style effects. This can best be done by studying monozygotic (MZ) twins discordant for obesity. MZ twins are genetically identical at the sequence level and any differences between the co-twins are thus attributable to environmental factors. The co-twin design controls for age, gender, childhood socioeconomic background and other environmental experiences and exposures.

Serum patterns of small molecules such as lipids reflect the homeostasis of the organism. However, classical measurements of lipids in the clinical setting are unable to detect early changes and abnormalities in specific metabolites. Recent advances have made broad screening of metabolites, i.e. metabolomics, feasible, therefore opening new possibilities for discoveries of sensitive biomarkers for different diseases.

The study convincingly demonstrates the sensitivity of the metabolomics platforms since subtle pathophysiological changes were detected well prior to changes in commonly utilized clinical measures. Of special interest and clinical relevance is the finding that the atherogenic lipid profile of the obese co-twins was associated with whole body insulin resistance, something that could not be detected using classical lipid measures only.

Obese children risk damaging feet structure

Fri, 24 Nov 2006 23:54:02 PST

( from http://www.rxpgnews.com ) London, Nov 24 - Obesity at childhood could damage the feet bones, leading to deformities, says a new study.

Each foot is made up of 26 bones, around 19 muscles, a large number of ligaments, tendons, blood vessels and nerves and is designed to absorb the shock of walking and running.

Excess weight and obesity can damage the delicate, immature nature of children's feet, leaving them at particular risk of deformities and abnormalities, said Stewart Morrison, a lecturer from the University of East London, who carried out the research found.

Researchers looked at 200 children from Glasgow aged nine to 12 years - 54 were obese and 15 were severely obese. Another 30 were overweight.

Obese children had feet that were up to 15 mm longer and seven mm wider than feet in normal weight children. In children with severe obesity, their feet were on average 18 mm longer and 15 mm wider, it said.

A second study of 44 nine-11 year olds, half of whom were obese, found that the obese children were unstable when they walked. They spent more time balancing on two feet when walking and less time on one foot than normal weight children. They also walked at a slower pace, it said.

'Obese children are less stable when walking and cannot walk efficiently,' Morrison said.

He added: 'The findings are interesting because previous research suggested that foot problems limit obese children's ability to take part in physical activity - so encouraging them to carry out exercise might not be the best thing.'

'This typifies the problems of obesity, showing it affects every part of the body,' Ian Campbell of the charity Weight Concern said.

Foot problems limiting the ability of obese children to exercise put them in a 'catch 22 situation' because they need to be more active, he said. 'This reinforces the need for prevention rather than cure, and for early intervention'.

Childrens Belly Fat Increases More Than 65 Percent

Tue, 07 Nov 2006 22:10:00 PST

( from http://www.rxpgnews.com ) Abdominal obesity increased more than 65 percent among boys and almost 70 percent among girls between 1988 and 2004. The finding of growing girth is significant because abdominal obesity has emerged as a better predictor of cardiovascular disease and type 2 diabetes risk than the more commonly used Body Mass Index, a weight to height ratio that can sometimes be misleading.

As the first nationally representative study to document the increase in childrens belly fat, the study in todays Pediatrics paints a bleak picture for these children who have a higher risk of heart disease, adult-onset diabetes and metabolic syndrome. The good news is that, for children and adolescents, the health effects are often reversible through improved lifestyle for weight loss.

Kids, teens and adults who have early stages of atherosclerosis in their arteries can have a healthy cardiovascular system again, said Stephen Cook, M.D., an assistant professor of Pediatrics at the University of Rochester Medical Centers Golisano Childrens Hospital at Strong and an author of the study about childhood abdominal obesity. Older adults who have plaque build up have a much harder battle, especially if the plaque has calcified.

Measuring waist circumference is not a vital sign normally taken in a visit to the doctor. A BMI is commonly calculated at a well visit, but there are limitations to those measurements. A very muscular person may register a high BMI score, even if he is very healthy and has an average waist circumference. On the flip side, a sedentary child may not register a very high BMI score, but if he carries a lot of fat around his middle, he may be at a higher risk for health problems than other children with the same BMI score.

Cook said there is no gold standard yet for how waist circumference should be measured and no consensus yet on the cut-off point for abdominal obesity. However, he added, the study should be a warning for physicians and parents to limit sedentary activities, such as TV and computer time, and to teach and model healthy eating and exercise behaviors; childhood obesity is a serious and growing problem perhaps even more than people already believe.

Although increases in Body Mass Index scores have raised concerns about U.S. childrens short- and long-term health, the increase in the percentage of abdominally obese in children appears to have increased even faster than overweight measured by BMI scores. According to data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004, the percentage of 6- to 11 year-old children with high BMI scores rose about 25 percent (15.1 percent in 1999-2000 to 18.8 percent in 2003-04). But the increase in abdominal obesity of the same group over the same period was even more dramatic, more than 35 percent (14.2 percent in 1999-2000 to 19.2 percent in 2003-04).

Those increases only grow more alarming as you tease out specific age groups over longer periods of time, Cook said. For example, between the 1988-1994 data and the 1999-2004 data, the largest relative increase in the prevalence of abdominal obesity occurred among 2- to 5-year old boys 84 percent and 18- to 19-year-old girls 126 percent.

Rising abdominal obesity among kids causes concern

Mon, 06 Nov 2006 16:44:00 PST

( from http://www.rxpgnews.com )

Abdominal obesity increased more than 65 percent among boys and almost 70 percent among girls between 1988 and 2004.

Abdominal obesity increased more than 65 percent among boys and almost 70 percent among girls between 1988 and 2004. The finding of growing girth is significant because abdominal obesity has emerged as a better predictor of cardiovascular disease and type 2 diabetes risk than the more commonly used Body Mass Index, a weight to height ratio that can sometimes be misleading.

As the first nationally representative study to document the increase in children's belly fat, the study in today's Pediatrics paints a bleak picture for these children who have a higher risk of heart disease, adult-onset diabetes and metabolic syndrome. The good news is that, for children and adolescents, the health effects are often reversible through improved lifestyle for weight loss.

"Kids, teens and adults who have early stages of atherosclerosis in their arteries can have a healthy cardiovascular system again," said Stephen Cook, M.D., an assistant professor of Pediatrics at the University of Rochester Medical Center's Golisano Children's Hospital at Strong and an author of the study about childhood abdominal obesity. "Older adults who have plaque build up have a much harder battle, especially if the plaque has calcified."

Measuring waist circumference is not a "vital sign" normally taken in a visit to the doctor. A BMI is commonly calculated at a well visit, but there are limitations to those measurements. A very muscular person may register a high BMI score, even if he is very healthy and has an average waist circumference. On the flip side, a sedentary child may not register a very high BMI score, but if he carries a lot of fat around his middle, he may be at a higher risk for health problems than other children with the same BMI score.

Cook said there is no gold standard yet for how waist circumference should be measured and no consensus yet on the cut-off point for abdominal obesity. However, he added, the study should be a warning for physicians and parents to limit sedentary activities, such as TV and computer time, and to teach and model healthy eating and exercise behaviors; childhood obesity is a serious and growing problem perhaps even more than people already believe.

Although increases in Body Mass Index scores have raised concerns about U.S. children's short- and long-term health, the increase in the percentage of abdominally obese in children appears to have increased even faster than overweight measured by BMI scores. According to data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004, the percentage of 6- to 11 year-old children with high BMI scores rose about 25 percent (15.1 percent in 1999-2000 to 18.8 percent in 2003-04). But the increase in abdominal obesity of the same group over the same period was even more dramatic, more than 35 percent (14.2 percent in 1999-2000 to 19.2 percent in 2003-04).

"Those increases only grow more alarming as you tease out specific age groups over longer periods of time," Cook said. "For example, between the 1988-1994 data and the 1999-2004 data, the largest relative increase in the prevalence of abdominal obesity occurred among 2- to 5-year old boys 84 percent and 18- to 19-year-old girls 126 percent."

Link between short sleep duration and obesity uncovered

Fri, 20 Oct 2006 22:51:00 PST

( from http://www.rxpgnews.com ) Soaring levels of obesity might be linked to children sleeping fewer hours at night than they used to, claims Dr Shahrad Taheri of the University of Bristol.

Dr Taheri, reporting in the Archives of Disease in Childhood, blames the increasing availability of computers, mobile phones, TVs and other such gadgets on the diminishing nightly quota of sleep, and suggests they should be banned from children's bedrooms.

Dr Taheri cites the emerging body of research on the impact on the body of a fall in the nightly quota of sleep, which reflects circumstances in real life, rather than sustained sleep deprivation, which tends to be more extreme.

This research shows that shorter sleep duration disturbs normal metabolism, which may contribute to obesity, insulin resistance, diabetes, and cardiovascular disease. Even two to three nights of shortened sleep can have profound effects, the laboratory data suggest.

One study indicated that insufficient sleep at the age of 30 months was associated with obesity at the age of seven, suggesting that this could programme the part of the brain regulating appetite and energy expenditure, says Dr Taheri.

But it is also a problem for teenagers in whom the need for sleep increases during this critical developmental period, he says.

Another piece of research shows that levels of leptin, a hormone produced by fat tissue when energy stores are low, were more than 15% lower in those sleeping five hours compared with those clocking up eight.

Similarly, ghrelin, a hormone released by the stomach to signal hunger was almost 15% higher in those with a five hour sleep quota.

Sleep loss also disturbs other hormones, including insulin, cortisol (stress hormone), and growth hormone, says Dr Taheri, who adds that hormonal changes could boost the desire for calorie rich foods.

And poor sleep sets up a vicious cycle. It leads to fatigue, which leads to reduced levels of physical activity, .which leads to lower energy expenditure, which leads to obesity, which itself leads to poor sleep, explains Taheri.

Dr Taheri acknowledges that the mechanisms behind obesity are likely to be complex. "Sleep is probably not the only answer to the obesity pandemic, but its effect should be taken seriously, as even small changes in energy balance are beneficial," he says. "Good sleep could be promoted by removal of gadget distractions from bedrooms and restricting their use," he suggests.

'Portion Distortion' may contribute to expanding waistlines

Sat, 02 Sep 2006 15:59:00 PST

( from http://www.rxpgnews.com ) New research shows that people's perceptions of normal portion sizes have changed in the past 20 years. A study out of Rutgers published in the September issue of the Journal of the American Dietetic Association reports that Portion Distortion may be the cause1. This phenomenon occurs when consumers perceive large portion sizes as appropriate amounts to eat at a single eating occasion.

"It has previously been established that portion sizes of virtually all foods and beverages served at restaurants and packaged for single-serve have dramatically increased over the last two decades," said Jaime Schwartz MS, RD, who was a graduate student at Rutgers at the time of this study. "Our study compared what people perceive to be a typical portion size now to what was perceived as typical two decades ago, before portions began to grow. We also compared current perceptions of typical portions to reference portion sizes, defined in this study as the serving size on the Nutrition Facts panel."

This study replicated one that was done 20 years ago in which participants were asked to serve themselves the amount they considered to be a typical portion of each meal item on a buffet table2. To follow this model, Schwartz and co-author, Carol Byrd-Bredbenner, PhD, RD, enrolled 177 young adults to participate. All were invited to attend one meal, selecting typical portions of a total of eight meal items at breakfast or six at lunch and dinner. Food and beverage choices mirrored the study of 20 years ago as to permit valid comparisons between typical portions over time.

Interestingly, most foods with drastically different portion sizes over the two decades were all served from and consumed from a cup or bowl. For example, typical portions of orange juice were more than 40 percent larger in the present day study than they were 20 years ago. In nutritional terms, this larger amount of orange juice provides 50 additional calories and could equal a five pound weight gain over the course of one year if consumed on a daily basis. Participants in the present study served themselves nearly 20 percent more cornflakes and poured almost 30 percent more milk on their cereal than participants 20 years ago.

On average, less than 45 percent of portions selected at the breakfast meal were within 25 percent of the reference portion size. For the lunch and dinner meals, around 30 percent of portions were within 25 percent of the reference portion size. This strongly suggests that the amount of food thought to be appropriate to eat at one sitting is different than what the Nutrition Facts panel indicates to be a single serving size. "With portions being distorted to this degree, it's no surprise that people's waistlines are expanding." Byrd-Bredbenner remarked.

The good news is that efforts to educate the public to limit certain foods that add excess calories may have been successful. For example, the typical portion size of salad dressing was significantly smaller in the current study than typical portions selected in the study done 20 years ago. The message that even nutritious foods (e.g., tossed salad) can become less healthy when calorically dense items (e.g., salad dressing) are used excessively, may have become well understood over the past two decades.

Although the causes of obesity are multifactorial, the incidence of obesity has increased over the past two decades in parallel with increasing portion sizes, and Portion Distortion may be a contributing factor. "Our society wants the 'bang for our buck' and when portions are served to us that we think are small we feel short-changed," commented Schwartz. "But we need to start 'undistorting' what we perceive to be a typical portion and begin to listen to our stomachs, not our eyes, to determine when to put the fork down."

Obese men are more likely to be infertile

Fri, 01 Sep 2006 18:08:00 PST

( from http://www.rxpgnews.com ) Men with increased body mass index (BMI) were significantly more likely to be infertile than normal-weight men, according to research conducted at the National Institute of Environmental Health Sciences (NIEHS), one of the National Institutes of Health.

"The data suggest that a 20-pound increase in men's weight may increase the chance of infertility by about 10 percent," says Markku Sallmen, lead author on the paper who is now at the Finnish Institute of Occupational Health. BMI is a number calculated from a person's weight and height. BMI provides a reliable indicator of body fatness for most people and is used to screen for weight categories that may lead to health problems.

The researchers studied couples enrolled in the Agricultural Health Study (AHS), a large project that began in 1993 examining factors that impact the health of farmers and their families in agricultural communities.

"Women who are overweight or obese tend to have a more difficult time becoming pregnant than normal-weight women, but whether men who are overweight or obese also have fertility problems had not been studied," says Donna Baird, Ph.D., an NIEHS epidemiologist with the study. The study is published in the September 2006 issue of Epidemiology.

The data on infertility and body mass came from questionnaires that 1,468 farmers and their wives completed when they enrolled in the study. The wives completed a family health questionnaire, which included information about the couple's reproductive history. The men reported their weight and height on a questionnaire about their health. The analysis was limited to couples with a pregnancy attempt during the four years before enrollment, and to women under the age of 40.

The researchers divided the couples into infertile and fertile groups. The infertile couples were those that tried for longer than a year to conceive, and the fertile couples were those that conceived within a year. The majority of men and women were more than 30 years old. Twenty-eight percent of the couples had experienced infertility.

Researchers found that men's BMI was an independent risk factor for infertility. The researchers adjusted for other factors that could affect fertility, including high BMI of the woman, age, cigarette smoking, alcohol intake, and solvent and pesticide exposure. After adjustment, there was a general increase in infertility with increased BMI, reaching a nearly 2-fold increase among obese men.

When researchers divided the sample into two equal groups by men's age, they found that men's BMI was a risk factor for infertility in both the older and younger men.

The researchers did not have data on frequency of sexual intercourse, so it is possible that overweight men have less sexual intercourse than their normal weight counterparts and this could influence fertility. However, there have been recent studies looking at semen characteristics that show lower semen quality for overweight and obese men, as well as hormonal differences.

"This study provides data on some additional health problems associated with obesity," said David A. Schwartz, M.D., director of the National Institute of Environmental Health Sciences. "Preventing obesity can help improve men's overall health, perhaps even their reproductive health."

The NIEHS unveiled a new strategic plan, "New Frontiers in Environmental Sciences and Human Health," in May aimed at challenging and energizing the scientific community to use environmental health sciences to understand the causes of disease and to improve human health. The plan can be accessed at http://www.niehs.nih.gov/external/plan2006.

Early-onset morbid obesity linked with low IQ scores

Fri, 01 Sep 2006 17:39:00 PST

( from http://www.rxpgnews.com ) University of Florida researchers have discovered a link between morbid obesity in toddlers and lower IQ scores, cognitive delays and brain lesions similar to those seen in Alzheimer's disease patients, a new study shows.

Although the cause of these cognitive impairments is still unknown, UF researchers suspect the metabolic disturbances obesity causes could be taking a toll on young brains, which are still developing and not fully protected, they write in an article published in the Journal of Pediatrics this month.

"It's well-known that obesity is associated with a number of other medical problems, such as diabetes, hypertension and elevated cholesterol," said Daniel J. Driscoll, M.D., Ph.D., a UF professor of pediatrics and molecular genetics and microbiology in the College of Medicine and the lead author of the study. "Now, we're postulating that early-onset morbid obesity and these metabolic, biochemical problems can also lead to cognitive impairment."

Researchers compared 18 children and adults with early-onset morbid obesity, which means they weighed at least 150 percent of their ideal body weight before they were 4, with 19 children and adults with Prader-Willi syndrome, and with 24 of their normal-weight siblings. Researchers chose lean siblings as a control group "because they share a socioeconomic group and genetic background," Driscoll said.

The links between cognitive impairments and Prader-Willi syndrome, a genetic disorder that causes people to eat nonstop and become morbidly obese at a very young age if not supervised, are well-established. But researchers were surprised to find that children and adults who had become obese as toddlers for no known genetic reason fared almost as poorly on IQ and achievement tests as Prader-Willi patients. Prader-Willi patients had an average IQ of 63 and patients with early-onset morbid obesity had an average of 78. The control group of siblings had an average IQ of 106, which falls within the range of what is considered normal intelligence.

"It was surprising to find that they had an average IQ score of 78, whereas their control siblings were 106," Driscoll said. "We feel this may be another complication of obesity that may not be reversible, so it's very important to watch what children eat even from a very young age. It's not just setting them up for problems later on, it could affect their learning potential now."

While performing head MRI scans of subjects, researchers also discovered white-matter lesions on the brains of many of the Prader-Willi and early-onset morbidly obese patients. White-matter lesions are typically found on the brains of adults who have developed Alzheimer's disease or in children with untreated phenylketonuria, the researchers wrote.

These lesions could be affecting food-seeking centers of the brain, causing the children to feel hungrier. But they are most likely a result of metabolic changes that damage the young, developing brain, Driscoll said.

More studies are needed to understand what is causing these cognitive impairments, said Merlin Butler, M.D., Ph.D., a professor of pediatrics at the University of Missouri and chief of genetics and molecular medicine at Children's Mercy Hospital and Clinics.

"This could be a really significant observation," Butler said. "It's an interesting concept. It's a whole new area of investigation."

The findings are preliminary and additional studies are planned, Driscoll said. Jennifer Miller, M.D., a UF assistant professor of pediatric endocrinology and the first author of the study, and other researchers from UF, All Children's Hospital in St. Petersburg, Fla., and Baylor College of Medicine also took part in the research.

Although there was no known genetic cause for early-onset morbid obesity in the subjects studied, Driscoll said there are likely genetic and hormonal factors at play that researchers have yet to discover, particularly since these children are becoming obese at a time when their parents still control what they eat. The researchers studied several sets of fraternal twins where one twin was lean and the other morbidly obese, yet their parents reported that each ate the same amount of food. In one case, the obese child actually ate less, Driscoll said.

Driscoll is also careful to point out that adults or children who become obese later in childhood are not at-risk for these cognitive impairments because their brains are sufficiently developed to fend off damage from obesity.

"We're all mindful that this is an obese society," he said. "We all need to be more careful with respect to what we eat, but in particular, that's very important for children under 4."

BMI is an unreliable indicator of obesity

Sat, 19 Aug 2006 17:34:00 PST

( from http://www.rxpgnews.com ) Body mass index (BMI) -- the commonly used measure of obesity - cannot reliably predict the outcome for patients with heart disease, concludes an Article in this week's issue of The Lancet. This is because BMI is an unreliable indicator of obesity, say the researchers.

Doctors already know that obesity is a risk factor for developing heart disease. However, how obesity affects people with established heart disease has been unclear because previous studies have had contradictory results.

To investigate, Francisco Lopez-Jimenez (Mayo Clinic College of Medicine, Rochester, MN, USA) and colleagues combined data from 40 studies involving about 250,000 people with heart disease; the average follow-up was four years. Most of the studies used BMI as a measure of obesity. (See Notes to editors) The investigators found that patients with a low BMI had a higher risk of death than those with a normal BMI. Overweight patients had better survival and fewer heart problems than those with a normal BMI. Obese people who had had bypass surgery had a higher death rate when compared with people with a normal BMI, while severely obese people had a higher risk of a heart-related death but not death from other causes.

The better outcomes for overweight people may be because they have more muscle than normal weight people, state the authors. The results therefore demonstrate the inability of BMI to discriminate between body fat and lean muscle, they conclude.

"Rather than proving that obesity is harmless, our data suggest that alternative methods might be needed to better characterise individuals who truly have excess body fat, compared with those in whom BMI is raised because of preserved muscle mass," explains Dr Lopez-Jimenez.

In an accompanying Comment Maria Grazia Franzosi (Istituto Mario Negri, Milan, Italy) states: "BMI can definitely be left aside as a clinical and epidemiological measure of cardiovascular riskUncertainty about the best index of obesity should not translate into uncertainty about the need for a prevention policy against excess bodyweight, which must be strongly supported."

Exercise important in reducing size of abdominal fat cells

Tue, 08 Aug 2006 04:31:00 PST

( from http://www.rxpgnews.com ) Reducing the size of abdominal fat cells which are a risk factor for diabetes and heart disease takes more than cutting calories, according to new research from Wake Forest University Baptist Medical Center. Early results from a five-year study show that exercise should be added to the equation.

"The message is very clear," said Tongjian You, Ph.D., instructor in geriatric medicine at Wake Forest Baptist and lead author. "Exercise is important to reducing the size of these cells, and may one day be part of a prescription for treating the health complications associated with abdominal fat."

The study is reported in the August issue of the International Journal of Obesity. The results from 45 obese, middle-age women with excess abdominal fat are part of an ongoing study of up to 125 women. The goal is to determine what lifestyle changes are needed to reduce the size of abdominal fat cells.

It is well known that overall obesity is a risk factor for diabetes and heart disease. Not all obese people develop these diseases, of course. Obese people who have more abdominal fat (an apple shape) are at a higher risk than people who store excess fat in their hips and thighs (a pear shape).

Abdominal fat is associated with metabolic syndrome, a cluster of symptoms that increases the risk for heart disease and diabetes. The syndrome is diagnosed when someone has at least three of the following: abdominal obesity, high triglycerides, low levels of high-density liprorotein ("good") cholesterol, high blood pressure and increased levels of sugar in the blood.

The current research studied a lesser-known risk factor for the syndrome the size of fat cells just under the surface of the skin, known as subcutaneous fat.

"The size of these fat cells predicts type 2 diabetes, independent of whether the patient is obese," said You.

Earlier studies had shown that exercise can reduce fat cell size, but it is not known if the intensity of exercise matters during dietary weight loss. For the current study, all women had a deficit of 2,800 calories a week, either through dieting or a combination of dieting and exercise.

One group cut their calorie levels through diet, but did not exercise. A second group walked at about 1 to 2 miles per hour on a treadmill for 50 minutes three times a week. A third group also walked three times a week, but at 3.5 to 4 miles per hour for 30 minutes. Both exercise groups burned 400 calories each week through walking.

The women were provided food for their lunch and supper, which was selected by a registered dietician. Body size and weight, as well as total fat and abdominal fat cell size were measured both before and after the 20-week study period. The results showed that all groups lowered their fat mass, body weight (by 19 to 23 pounds), percent fat, and waist and hip girths (by 3 to 4 inches in hips and 4 inches in waists) to a similar degree.

The diet-alone group had no changes in abdominal fat cell size. However, both exercise groups had decreases of about 18 percent in the size of their abdominal fat cells.

"It is important to complete our larger study to see if these results hold true," said You. "But, these early findings do point to the importance of exercise in treating the complications of abdominal fat."

You said it's possible that because of the small size of the study, women in the diet-alone group did have small reductions in fat cell size that weren't detected. "However, considering the important role of abdominal fat cell size in predicting diabetes and heart disease, our study does indicate that addition of exercise to dietary weight loss is more beneficial than weight loss alone," he said.

High BMI doesn't always spell obesity

Sat, 22 Jul 2006 19:26:00 PST

( from http://www.rxpgnews.com ) For years doctors have used the body mass index (BMI), a ratio of height and weight, to characterize the clinical weight status of their patients. The lower the number, the presumption goes, the leaner the person, and anyone with a BMI above 30 is characterized as obese and at high risk for the associated complications.

But the BMI has come under scrutiny lately, and other techniques that measure how the weight is distributed on the body are thought to provide a better way to assess risk. Now a study in mice by scientists at The Jackson Laboratory indicates that the usefulness of the BMI is suspect even at the genetic level.

In research published in PLoS Genetics, the investigators from Jackson and the J.L. Pettis VA Medical Center and led by Dr. Gary Churchill of Jackson used a combination of computational, molecular and genetic tools to identify locations on the mouse genome that influence adiposity (amount of body fat), overall body size and bone structure. Applying an analytical technique called "structural equation modeling" to the genetic and physical characteristics of mouse inbred crosses, the scientists went beyond the one-gene, one-trait approach to reveal the networks of effects created by the influence of multiple genes.

"We found that the genetic network affecting adiposity is separate from that affecting overall body size," Churchill says, "providing strong evidence that a high weight is not necessarily directly associated with a high percentage of fat."

At the clinical level, the research suggests that more refined measurements are needed to distinguish individuals with a large body mass from those who are truly obese and consequently at high risk for diabetes, heart disease and other disorders.

Churchill and colleagues at Jackson recently received a 5-year, $15.1 million National Institute of General Medical Sciences grant to form an interdisciplinary Center for Genome Dynamics to study complex biomedical problems. "The most common diseases and health disorders, including obesity as well as heart disease, diabetes and cancer, result from an interaction of multiple genes and environmental factors that add up to a dauntingly complex mix of variables," Churchill says. "We're working to unravel those factors to lay the groundwork for improved treatments."

Health Risks in Obesity are Underestimated

Wed, 05 Jul 2006 19:04:00 PST

( from http://www.rxpgnews.com ) The health risks for women who are extremely obese may be underestimated as a new study indicates they have a higher prevalence of hypertension, diabetes, and high cholesterol than women at lower levels of obesity, according to a study in the July 5 issue of JAMA.

Obesity diagnosis and treatment are typically based on body mass index (BMI) of at least 30. BMI is calculated as weight in kilograms divided by height in meters squared. However, three categories of obesity are defined: obesity 1 (30-34.9); obesity 2 (35-39.9); and extreme obesity (40 and greater). (A 54 person would have a BMI of 40 if they weighed 233 lbs). The latter 2 categories, sometimes termed severe obesity, are reported to be increasing especially rapidly in the United States, according to background information in the article. From 1986 to 2000, prevalence of BMI of 30 or higher approximately doubled, while that of BMI of 40 or higher quadrupled and that of BMI of 50 or higher increased 5-fold. In 2000, 2.8 percent of all U.S. women, and 6 percent of black women reported measurements consistent with extreme obesity. Estimates of obesity-related risks in women have generally been based on weight data that preceded the increase in extreme obesity. It has been unclear whether health risk increases or plateaus as body weight increases throughout the obese range.

Kathleen McTigue, M.D., M.S., M.P.H., of the University of Pittsburgh, and colleagues conducted a study to examine the relationship between weight category and risk of death and coronary heart disease (CHD) in a large population-based sample of U.S. women, focusing on risk across degree of obesity. The researchers analyzed data on incident death and cardiovascular outcomes by weight status in 90,185 women recruited from 40 U.S. centers for the Womens Health Initiative-Observational Study who were followed-up for an average of 7.0 years (Oct. 1993 to Aug. 2004).

The researchers found that extreme obesity prevalence differed with race/ethnicity, from 1 percent among Asian and Pacific Islanders to 10 percent among black women. In this diverse population-based sample of older women, we found that obesity was linked with considerable health risk and that accounting for degree of excess weight is important in understanding weight-related health risk. Overall, extremely obese women were more likely to die over the average 7.0 years of follow-up than were women in other examined weight categories. Modeling analyses adjusted for age, smoking status, educational achievement, U.S. region, and physical activity level showed that weight-related risk for all-cause mortality, CHD mortality, and CHD incidence did not differ by race/ethnicity.

There was a positive trend in all-cause mortality risk and CHD incidence with increasing weight category. This trend had borderline significance for CHD mortality among black women, likely reflecting sample size limitations. Much of the obesity-related mortality and CHD risk was mediated by diabetes, hypertension, and hyperlipidemia [high cholesterol levels]. In white women, as other studies have found, weight-related all-cause mortality risk was modified by age, with obesity conferring less risk among older women. Smoking may modify weight-related risk in black women, but further study is needed to understand the nature of this relationship, the authors write.

Our findings have important clinical and policy implications. The escalating prevalence of extreme obesity may exacerbate the health effects and health-related expenditures resulting from the U.S. obesity epidemic. Calculating the weight-related risks of morbidity and mortality based on findings in earlier population samples, which tended to reflect lower degrees of obesity, may underestimate the risks for extremely obese individuals and overestimate the risks for mildly obese individuals in diverse groups, the researchers write. More accurately assessing weight-related health risk may both improve policy decisions about obesity and assist women in making informed decisions about their health.

Significant link between obesity and depression

Wed, 05 Jul 2006 19:00:00 PST

( from http://www.rxpgnews.com ) There is a strong link between obesity and mood and anxiety disorders, especially among Caucasian Americans and those with more education and higher income, according to an analysis conducted by researchers from Group Health Center for Health Studies.

The study, published in the July issue of the Archives of General Psychiatry, found that an obese person is about 25 percent more likely than a non-obese person to have a mood or anxiety disorder, such as depression. It also indicated that among Caucasian Americans and more educated people who are obese, that likelihood may be as high as 44 percent.

While the study did not show whether obesity leads to depression or vice versa, its almost certain that the association works in both directions, said Greg Simon, MD, MPH, a Group Health psychiatrist and the lead author of the study.

The researchers also found a negative association between obesity and substance abuse. That is, an obese person is 25 percent less likely than a non-obese person to have had a substance abuse disorder sometime in their lives.

Understanding the connection between obesity and depression is an important public health issue because both of these conditions are so common and have a significant impact on our health care systems, Dr. Simon explained.

He pointed to the evidence that an average American has a 30 percent chance of being obese. This study shows that when a person is depressed, the odds of also becoming obese are as high as 40 percent.

About 20 percent of Americans are diagnosed sometime in their lives with depression. Among those who are obese, that likelihood of depression jumps to 28 percent, said Dr. Simon.

The study is based on an in-person survey that the researchers from Harvard Medical School conducted among a nationally representative sample of 9,125 adult men and women. Obesity is defined in the study as having a body mass index (BMI) of 30 or more.

While previous studies have shown a connection between obesity and depression, this is the largest and most representative study of the two problems in U.S. population. Also, this study included a much more careful assessment of mental health problems than earlier research, according to Dr. Simon.

Unlike many previous studies that show a link between obesity and depression among women only, this study revealed a strong link in both genders. There were significant differences among social and cultural groups. In groups where obesity is more commonthat is, among non-white and less educated groupsthere is less depression among the people who are obese. But in groups where there is less obesity, it is accompanied by more depression.

This may indicate that stigma accounts for some of the relationship between obesity and depression, said Dr. Simon. Perhaps in groups where obesity is less socially normative, its less acceptable and thats why theres a greater association with depression, he suggested. But in groups where it is less stigmatized, obesity doesnt seem to be as depressing.

Strong Heart study (SHS): Bigger, heavier hearts portend heart disease risk even before adulthood

Sat, 03 Jun 2006 09:00:00 PST

( from http://www.rxpgnews.com ) The effects of excess weight on heart health can be seen even in adolescents, with abnormal enlargement and impaired pumping function evident in subjects by age 20, according to a new study in the June 6, 2006, issue of the Journal of the American College of Cardiology.

"Heart damage starts very early in the natural history of obesity. We need to work on our young people, to prevent catastrophic effects later on," said Giovanni de Simone, M.D., F.A.C.C. from the New York Presbyterian Hospital-Weill Medical College of Cornell University in New York, New York and the Federico II University Hospital School of Medicine in Naples, Italy.

The Strong Heart study (SHS) is a longitudinal study of cardiovascular risk factors and cardiovascular disease that enrolled 4,549 people in American Indian communities in Arizona, Oklahoma, and North and South Dakota. This analysis included data from examinations of 460 participants age 14 to 20 years (245 girls and 215 boys). The researchers used ultrasound and other methods to measure the size, shape and pumping function of the teenagers' hearts.

The left ventricles of the hearts of both overweight and obese teenagers were larger and heavier than those of normal weight participants; but the obese teenagers also showed signs of impaired heart function. The changes were not entirely explained by changes by high blood pressure.

"Our findings demonstrate that, even among adolescents at a mean age under 18, severity of abnormality in body build also parallels early cardiac changes, including high prevalence of left ventricular hypertrophy and increased hemodynamic load, paralleling previous findings and suggesting that increased left ventricular mass occurs to sustain the increased cardiac workload," the study authors wrote.

"The main findings are that, when obesity is present, something happens in our hearts to increase its size and wall thickness, which cannot be understood by measurement of blood pressure. This excess of cardiac mass, which we call 'inappropriate' in connection to cardiac workload, is also associated with a general impairment of the function of the heart to push blood into the arterial tree and also to distend its cavity to receive the blood returning from the periphery," Dr. de Simone said.

He said that these results underscore the need to fight excess weight in children, since the damaging effects are evident even before adulthood.

Although the participants in this study were all members of American Indian communities, Dr. de Simone said that he believes similar effects would be seen in overweight and obese children from other communities.

"The analysis was performed in an American Indian population and whether these results can be generalized to other ethnic groups needs to be demonstrated. However, similar analyses previously performed in other ethnic groups, such as Caucasians and African Americans, have suggested similar association between left ventricular mass and adiposity, independently of other cardiovascular risk factors," the authors wrote.

In an editorial in the journal, Stephan von Haehling, M.D., Wolfram Doehner, M.D., Ph.D., and Stefan D. Anker, M.D., Ph.D. from the Imperial College School of Medicine in London, United Kingdom and the Charité Medical School and Campus Virchow-Klinikum in Berlin, Germany wrote that the results from this study are in line with those from other studies that have documented that overweight and obese children and adolescents tend to have enlarged hearts and that enlarged hearts are a sign of increased risk of chronic heart failure.

"But patients with chronic heart failure, who have a poor prognosis per se, appear to benefit from being overweight. The most intriguing question in this respect is to define a time point after which obesity does not pose as a risk factor anymore," the editorial authors wrote.

"For young people with presence of established risk factors for future cardiovascular illness (like hypertension, hyperlipidemia or diabetes), it seems very likely that obesity confers a somewhat higher risk for death compared with such people with normal weight. Whether the same is true for older people is not known. We hypothesize that obesity carries no adverse mortality impact above the age of 60 years--possibly even from age 55 to 50 years. This remains to be tested," they added.

Robert J Bryg, M.D. from the University of Nevada School of Medicine, who was not connected to this study, said it demonstrates that there are significant cardiac consequences of childhood obesity.

"The increased left ventricular mass and left ventricular hypertrophy would suggest that long term consequences will occur in this cohort. Even though this is a population of Native Americans, I still believe that it is generalizable to the overall US population. This suggests that the epidemic of obesity in the US will have long term consequences on heart disease in this country," Dr. Bryg said.

Commercial diets are a useful way to lose weight

Fri, 02 Jun 2006 23:02:00 PST

( from http://www.rxpgnews.com ) Commercial diets are a useful way to lose weight. And those based on group support seem to fare better at keeping the weight off in the long term, finds a study in this weeks BMJ.

Researchers compared the effectiveness of four popular commercial weight loss programmes with a control group. The study was sponsored by the BBC as part of its reality TV series, BBC Diet Trials.

The diets were the Slim-Fast Plan (a meal replacement approach), Weight Watchers pure points programme (an energy controlled diet with weekly group meetings), Dr Atkins new diet revolution (a self-monitored low carbohydrate eating plan), and Rosemary Conleys eat yourself slim diet and fitness plan (a low fat diet and weekly exercise class). The control group was asked to maintain their current diet and exercise pattern.

Weight and body fat changes were monitored over six months and dieting behaviour was checked again at 12 months.

After six months, all diets resulted in significant loss of body fat and weight compared to the control group. Average weight loss was 5.9 kg and average fat loss was 4.4. kg (5-10% of body weight). The Atkins diet resulted in significantly higher weight loss during the first four weeks, but by the end, was no more or less effective than the other diets.

There were no significant differences in cardiac risk factors between the diet groups and the control group. The Atkins diet did not lead to substantial increases in cholesterol levels.

At 12 months, 158 participants (54% of the original sample) returned data. Only 58 (45%) were still keeping to their allocated diets (nine to Atkins, 20 to Weight Watchers, nine to Slim-Fast, 20 to Rosemary Conley). More participants in the unsupported programmes (Atkins diet and Slim-Fast) withdrew from the study than in the supported group based programmes, and weight rebound after the initial six months was higher in the unsupported programmes.

The authors conclude that clinically useful weight loss and fat loss can be achieved in adults who are motivated to follow commercial diets for a substantial period. People need to find a diet that best suits them.

Our study provides data on how much weight patients can expect to lose by dieting, they write. These data could help practitioners in managing patients expectations of weight loss targets.

An accompanying editorial suggests that the challenge to researchers is to take weight loss studies to the next level by evaluating long term health outcomes, cost effectiveness, and novel strategies of improving adherence and weight maintenance.

New study shows some people just cant resist food

Fri, 02 Jun 2006 22:51:00 PST

( from http://www.rxpgnews.com ) Scientists have discovered why some peoples brains are particularly vulnerable to food advertising and product packaging, putting them at risk of overeating and becoming overweight. The research provides fresh insight into one of the neurobiological factors underlying obesity by showing how some people are more attracted to the prospect of being rewarded with tasty food than others. The findings from a group of scientists at the Medical Research Councils Cognition and Brain Sciences Unit in Cambridge led by Andy Calder and Andrew Lawrence are published in the Journal of Neuroscience.

Different people have higher or lower reward sensitivity, a personality trait that reflects a general desire to pursue rewarding or pleasurable experiences. The research shows that individuals with higher reward sensitivity, show increased activity in the parts of the brain implicated in motivation or reward when simply looking at pictures of appetizing food.

Previous research has shown that people with high reward sensitivity have stronger food cravings and are more likely to be overweight, but until now, the biological basis of this effect was unknown. This new research identifies how this relationship operates in the human brain, resulting in greater susceptibility to food advertising.

The study used the latest technology in brain imaging. The researchers showed people pictures of highly appetizing foods (e.g. chocolate cakes), bland foods (e.g. broccoli), and disgusting foods (e.g. rotten meat) while measuring brain activity using an fMRI scanner. After testing, the study participants completed a questionnaire that assessed their general desire to pursue rewarding items or goals. The results showed that the participants scores on the reward sensitivity questionnaire predicted the extent to which the appetizing food images activated their brains reward network.

Previous studies in this area have assumed that brain activation patterns are similar in all healthy individuals. But the new findings demonstrate that even in healthy individuals some peoples brain reward centers are more sensitive to appetizing food cues. This helps explain why some individuals are more vulnerable to developing certain disorders like binge-eating, said Dr John Beaver, lead author of the study.

This is particularly pertinent in understanding the rapidly increasing prevalence of obesity, as people are constantly bombarded with images of appetizing food items in order to promote food intake through television advertising, vending machines, or product packaging.

According to Dr Beaver the findings may also have broader implications for understanding vulnerability to multiple forms of addiction and compulsive behaviors.

Research demonstrates that an individuals reward sensitivity may also relate to their vulnerability to substance abuse, and the brain network we have identified is hyper-responsive to drug cues in addicts, he said.

Separate mechanisms in metabolic syndrome- Akt and atypical PKC

Sun, 14 May 2006 18:55:00 PST

( from http://www.rxpgnews.com ) Insulin uses two distinct mechanisms to control glucose and the metabolism of blood fats (lipids) in the liver, a new Joslin Diabetes Center-led study has discovered. Failures in each of these networks can lead to serious health problems: the breakdown of glucose metabolism that can lead to type 2 diabetes, and the malfunction of lipid metabolism contributing to metabolic syndrome, which is a cluster of conditions that puts people at increased risk of heart disease, vascular disease and type 2 diabetes.
The new study, led by C. Ronald Kahn, M.D., and Cullen Taniguchi, M.D., Ph.D., of Joslin Diabetes Center in Boston and their colleagues, is published in the May edition of Cell Metabolism. The findings open the door to the development of new treatments that one day may target directly the conditions that contribute to type 2 diabetes and the metabolic syndrome.

"Patients with the metabolic syndrome have high levels of both glucose and lipids in the blood. We now understand that insulin that controls the pathways that control glucose levels are different from those that regulate lipid levels. By targeting these specific pathways, we might be able to improve problems with glucose metabolism, lipid metabolism or both," says Dr. Kahn, President of Joslin Diabetes Center and Mary K. Iacocca Professor of Medicine at Harvard Medical School.

Diabetes affects an estimated 20.8 million children and adults in the United States -- 7 percent of the population. An estimated 14.6 million Americans have been diagnosed, leaving 6.2 million Americans unaware that they have the disease. In addition, 41 million Americans are thought to have pre-diabetes, or elevated blood glucose levels that put them at risk for developing type 2 diabetes. If untreated or poorly treated, diabetes can lead to blindness, kidney disease, stroke, nerve damage and circulation problems that can result in limb amputations.

Patients generally are diagnosed with metabolic syndrome if they have three or more of the following conditions: abdominal obesity; high cholesterol levels or triglycerides; low levels of good cholesterol; high blood pressure; and high blood glucose. The metabolic syndrome has become increasingly common in the United States, and according to a recent survey, is seen in 24 percent of all adult Americans above age 20 and in about 40 percent of those above age 60.

Exploring the role of the liver The liver is the body's primary chemical factory, and among its key roles is keeping glucose levels in the blood constant between meals. The liver also produces and packages cholesterol and triglycerides to send throughout the body. Insulin's activity in the liver controls both of these processes, but, until now, researchers have not understood how insulin does its job.

"In one of its roles, insulin tells the liver that you have just eaten, that it can stop producing glucose since the food you have just eaten will, for a while, supply an adequate amount," says Dr. Taniguchi, a postdoctoral fellow in Joslin's Section on Cellular and Molecular Physiology and lead author of the paper. "Insulin also is the trigger that tells the liver how to handle lipids. We have been trying for many years to understand how insulin provides these signals, and now we have shown that insulin controls each process differently."

Insulin drives the liver's metabolic functions by activating a molecule called phosphoinositide 3-kinase (PI3K), which then recruits other enzymes to carry out its orders. While researchers knew that the PI3K pathway was important to insulin's action, until now they didn't know how insulin uses PI3K to control either glucose or lipid metabolism.

Using mice bred to lack specific subunits of the PI3K pathway, the researchers discovered that mice that could not activate the protein kinase Akt had increased glucose production in the liver, impaired glucose tolerance, and increased levels of insulin in the blood, all contributors to type 2 diabetes. On the other hand, those mice with defects in the atypical forms of the enzyme protein kinase C (PKC) had decreased lipids in the blood and reduced levels of a protein called SREBP, which is critical for regulating fatty acid and cholesterol in the blood. (This particular form of the PKC enzyme is distinct from the form known as PKC-beta, which is activated by high blood glucose and is linked to many diabetic complications, including those of the eye and the blood vessels.)

"People used to think that Akt controlled both glucose and the lipids in the liver," says Dr. Taniguchi. "Now we know that Akt has nothing to do with the lipids. Akt controls the glucose part and the atypical PKC controls the lipids part." He explains that some patients with fatty liver disease don't have any glucose problems, while others with type 2 diabetes don't have problems with their lipids. "Now that we have uncovered the important molecules for each condition," says Dr. Taniguchi, "we can begin to look for ways to specifically target just the lipids or just the glucose."

Development of adiposity in adolescence in Britain

Wed, 10 May 2006 02:47:00 PST

( from http://www.rxpgnews.com ) The idea that puppy fat in children disappears as they progress to adolescence is a myth which may put the future health of children at risk, says a paper published on bmj.com.

And girls from some ethnic minorities and lower socioeconomic groups are more likely to be overweight or obese, putting them at even more danger of long-term health problems, say the authors.

Previous studies have shown that adolescence is a key time, since excess weight during teenage years pre-disposes adults to continued weight problems - with all the associated health risks.

But todays study, tracking 5863 children as they developed into young adults, shows that the problems are established before teenage years - since those with excess weight by the age of 11 continued with it during adolescence.

Researchers looked at annual measurements of weight, height, Body Mass Index (BMI) and waist circumferences of children aged between 11/12 and 16/17 throughout 36 schools across South London, giving them a broad ethnic and social mix.

They found that overall, girls had higher rates of excess weight problems than boys. Black girls had particularly high levels, with an average of 38% being overweight or obese over the study period, compared to 28% for white girls or 20% for Asian girls.

For boys, however, ethnicity made little difference to excess weight levels.

The findings were less clear cut for economic status. 35% of the most deprived girls were overweight or obese compared with 28% of other girls, but other economic categories showed less consistency.

Children who are obese when they enter secondary school will very likely leave it obese, say the authors. More monitoring is crucial if rising tides of obesity are to be tackled effectively, they conclude.

New clinical team approach reduced cardiovascular risk for obese metabolic syndrome patients

Mon, 01 May 2006 00:47:00 PST

( from http://www.rxpgnews.com ) Obesity researchers at the Medical College of Wisconsin in Milwaukee found that a multidisciplinary clinical approach to caring for obese patients with metabolic syndrome could swiftly and significantly lower their risk for heart disease.

The research found that such care could lower their ten-year risk for cardiovascular disease by nearly 20 percent within six months. It will be presented in a poster session, at the American Association of Clinical Endocrinologists Annual Meeting, in Chicago, April 28.

The study was conducted by Safak Guven, M.D., assistant professor of medicine at the Medical College and clinical director of the Obesity/Metabolic Syndrome Clinic at Froedtert Hospital, a major teaching affiliate of the Medical College, in collaboration with the University of Wisconsin School of Pharmacy.

"This study highlights the benefits of a clinic that specializes in the needs of obese patients with metabolic syndrome" says Dr. Guven. "Metabolic syndrome affects approximately 24 percent of the US adult population; according to the Third National Health and Nutrition Examination Survey criteria. About 47 million people have metabolic syndrome, including 44 percent of those who are ages 50 and older. Metabolic syndrome (without type 2 diabetes) significantly increases the risk of coronary heart disease (CHD).

The research could also help establish national clinical standards of care for metabolic syndrome, and accreditation for clinics treating this rapidly emerging problem. "Studies have shown that patients with metabolic syndrome are 1.5 times at greater risk for CHD," says Dr. Guven. "On the other hand, women in reproductive ages with metabolic syndrome are prone to have polycystic ovarian syndrome, which also puts them at risk for fertility issues. In other words, your waistline now has a significant impact on your lifeline."

Metabolic syndrome is a dangerous constellation of problems occurring in abdominally obese, insulin-resistant patients, with or without type 2 diabetes, and having any of several conditions, including cholesterol abnormalities, hypertension, clotting, or inflammatory protein factors in their blood. This leaves them extremely vulnerable to cardiovascular diseases caused by plaque deposits. These include coronary and/or peripheral artery disease and strokes.

The team reviewed charts of over 480 patients treated in the recently-developed obesity and metabolic syndrome clinic at Froedtert Hospital and found 46 obese patients who met the criteria for the study.

Outcomes data on these patients revealed that, after six months of treatment, their collective body mass index dropped 4.4 percent, their waist size 4.3 percent, their triglycerides (harmful fatty acids) dropped 13.1 percent and their HDL (beneficial) cholesterol level rose 6.2 percent. As a result, their ten-year risk of developing cardiovascular disease, based on scoring criteria established by the National Heart Lung and Blood Institutes' landmark Framingham Heart Study,* was reduced by 19.5 percent.

Obesity may increase diabetes risk

Sat, 22 Apr 2006 17:48:00 PST

( from http://www.rxpgnews.com ) People who are obese may be at increasing risk of getting diabetes, says a study that reiterates the belief that a change in lifestyle could help.

Linda S. Geiss from US' Center for Disease Control and Prevention and other researchers analysed data collected every year from a national sample of 31,000 Americans, reported the online edition health magazine WebMD.

In addition to detailed health and demographic data, they also asked each person if he or she had ever been told by a health professional that they have diabetes.

The researchers found that people with diabetes overwhelmingly tend to have one thing in common: being obese or overweight.

From 1997 to 2003, there was a 41 percent increase in the incidence of diagnosed diabetes. In 2003, two out of every 1,000 normal weight people had diabetes.

In the same year, diabetes struck 18.3 out of every 1,000 obese people, and 5.5 out of every 1,000 overweight people, the researchers said.

Obesity is by far the best predictor of being newly diagnosed with diabetes. But it's not the only one.

"Age, race, and educational level all are associated with diabetes," Geiss says. There's not much you can do about your race or your age. There is a lot you can do about your weight-related diabetes risk.

"Diabetes can be prevented among people at high risk." It will take some minor but admittedly difficult lifestyle changes: becoming active, and losing a little bit of weight.

Study finds crucial link between obesity, heart disease

Tue, 18 Apr 2006 07:13:00 PST

( from http://www.rxpgnews.com ) Fat cells around coronary arteries release chemicals that could trigger inflammation leading to deterioration of the vessels, says a new study that may provide the crucial link between obesity and heart disease.

The study by researchers at University of Iowa found that fat cells lying close to blood vessels in the heart are highly active, releasing many chemicals that influence biological processes within the body, reported the online edition of BBC News.

Fat cells or adipocytes, were once thought to do nothing other than simply store excess fat tissue.

Most large blood vessels in the body are enveloped in a layer of fat cells. The researchers suspect that the chemicals pumped out by the fat cells surrounding the coronary arteries might play a role in triggering heart disease by contributing to the deterioration of these vessels.

Lead researcher Lynn Stoll said: "The fat cells surrounding coronary arteries may ultimately prove to be an important link between obesity, type two diabetes, and coronary artery disease, all of which are increasing at epidemic rates."

The findings were presented to the Experimental Biology 2006 conference in San Francisco.

"It has been recognised for several years that fat cells stored up around the body secrete hormones that affect blood vessel function, but this is the first time that researchers have paid careful attention to fat cells lying close to blood vessels in the heart," said Jeremy Pearson, associate medical director of the British Heart Foundation.

Study warns of growing Metabolic syndrome epidemic in China

Sat, 15 Apr 2006 09:58:00 PST

( from http://www.rxpgnews.com ) As more people in China adopt Western diets and lifestyles, many are developing a cluster of cardiovascular disease risk factors, according to a new study in the April 18, 2006, issue of the Journal of the American College of Cardiology.

"The metabolic syndrome has become increasingly common in this Asian population and the prevalence is about to catch up with that in Western populations. That's a very dangerous sign in terms of cardiovascular disease," said Frank B. Hu, M.D., Ph.D. from the Harvard School of Public Health in Boston, Massachusetts.

The researchers, including lead author Yao He, M.D., Ph.D. from Harvard and also the Chinese PLA General Hospital in Beijing, China, interviewed and examined 2,334 people age 60 years or older who lived in the Beijing metropolitan area. Almost a third to almost half of the participants had metabolic syndrome. Metabolic syndrome is a cluster of five risk factors: central obesity defined by waist circumference, high blood pressure, low HDL ("good" cholesterol), high triglycerides, and high blood sugar.

"There have been some reports from developing countries, including China, on the prevalence of metabolic syndrome, but this is actually the first study to look at the urban elderly population in a systematic way and to document not only the prevalence of metabolic syndrome, but also its relationship with cardiovascular disease," Dr. Hu said.

According to the definition of metabolic disease from the U.S. National Cholesterol Education Program (NCEP), just over 30 percent of the participants had metabolic syndrome. However, 46 percent of the people in this study met the criteria for metabolic syndrome used by the International Diabetes Federation (IDF). The presence of metabolic syndrome was also associated with higher prevalence of cardiovascular disease.

"Using the IDF definition, the prevalence of metabolic syndrome increased substantially, because a lower cut-off point for central obesity was used. And what's interesting is that in this study it appears that metabolic syndrome as defined by the IDF is more strongly correlated with cardiovascular disease, including heart disease, stroke and peripheral artery disease, than the metabolic syndrome defined by the U.S. National Cholesterol Education Program criteria," Dr. Hu said. "This is not surprising given that Chinese people develop diabetes and cardiovascular disease at much lower BMI (Body Mass Index) compared to Caucasians."

Dr. Hu said the findings indicate that as the economy and lifestyles in China become more westernized, people in China are also developing "western" patterns of cardiovascular disease risk.

"So the population is undergoing the transition from under-nutrition to over-nutrition and from underweight to obesity. In the next several decades, I think the obesity problem will get worse and the prevalence of metabolic syndrome and also its consequences, such as diabetes and cardiovascular disease, will continue to increase. This will create a huge burden for the health care system," Dr. Hu said.

Dr. Hu pointed out that this study just took a snapshot of the health of a selected urban population. He said future studies should follow people in China over time to track metabolic syndrome and how well it predicts the development of diabetes and cardiovascular disease.

In the meantime, he urged clinicians to look beyond the diagnosis and treatment of individual risk factors, such as high blood pressure, and instead pay closer attention to preventing and treating the cluster of risk factors that make up the metabolic syndrome.

"Chronic non-communicable disease is increasingly becoming prevalent in China, especially in cities such as Beijing, due to changing of dietary patterns and lifestyle," he said. "The future burden from cardiovascular disease or other chronic disease in China will be substantial."

Dr. Chen pointed out that this study is just a first step toward understanding metabolic syndrome and cardiovascular disease in China.

"This study is relatively small and, as discussed in the paper, it is only a cross-sectional study. A large prospective study in China is needed to assess the relationship between metabolic syndrome and risk of cardiovascular disease mortality and incidence," he said.

INSIG2 - Genetic component in obesity identified

Fri, 14 Apr 2006 22:34:00 PST

( from http://www.rxpgnews.com ) US scientists have identified a genetic change in a region of the DNA related to fat production, which they say could help in new treatments for obesity.

More than one-third of people in the US are obese and the population of other countries are increasingly facing similar weight issues.

Albert Herbert and fellow researchers at the Boston University Medical School identified a small genetic change in a region of DNA near a gene known as INSIG2 as being linked to obesity, reported the online edition of New Scientist.

The DNA code is made up of four bases, or "letters". A single change in this particular region, from a G to a C, makes a person more prone to obesity, the study says.

The researchers looked at almost 87,000 points in the human genome which show variation between individuals, and related this to the body mass index (BMI) of over 900 people.

The team found one particular genetic variation near the INSIG2 gene. This change somehow affects the regulation of the gene INSIG2, which they say has a role in fat production.

In follow-up studies involving about 9,000 individuals in total, they also found the same association.

The researchers said that an individual with two copies of the C variant is 22 percent more likely to have a BMI greater than 30 - the point where people move from being "overweight" to "obese".

They hope that their discovery will open doors to new treatments for the condition.

Selective photothermolysis - US scientists on path towards 'fat seeking' laser

Tue, 11 Apr 2006 14:14:00 PST

( from http://www.rxpgnews.com ) Scientists in the US have developed a laser that can melt pig fat and possibly be used to treat heart disease, cellulite and acne in humans in the future.

Professor Rox Anderson and other researchers at the Massachusetts General Hospital used pig fat and skin samples about two inches thick in their experiment and found that a laser is, for the first time, able to heat up fat in the body without harming the overlying skin, reported the online edition of BBC News.

Using the Free-Electron Laser at selected wavelengths, they were able to heat the fat up, which was then broken down and excreted by the body, it said.

Selective photothermolysis - heating tissues with light - could have medical applications in the future, including for treating acne, Anderson said.

The root cause of acne is the lipid-rich sebaceous gland, which sits a few millimetres below the surface of the skin.

"We want to be able to selectively target the sebaceous gland and this research shows that, if we can build lasers at this region of the spectrum, we may be able to do that, Anderson said.

Cellulite and body fat could also be targeted as well as the fatty plaques that form in arteries, leading to heart attacks, he said.

"We can envision a fat-seeking laser, and we're heading down that path now," he added.

However, researchers said it would be several years before the technique could be tested on humans.

Excess Television May Lead To Extra Weight For Preschoolers

Wed, 05 Apr 2006 19:23:00 PST

( from http://www.rxpgnews.com ) In a national study of more than one thousand preschool-age children, those who were exposed to more than two hours of television per day were more likely to be overweight at ages 36 and 54 months than those who were exposed to less than two hours of television per day, according to a study in the April issue of the Archives of Pediatrics & Adolescent Medicine, a theme issue on children and the media.

The American Academy of Pediatrics recommends that children aged 2 years and older be limited to less than two hours of total media time per day, according to background information in the article. Studies have linked excessive television viewing to a variety of problems, including risk of being overweight. However, most research has focused on school-aged rather than preschool-aged children.

Julie C. Lumeng, M.D., University of Michigan, Ann Arbor, and colleagues studied 1,016 children from 10 urban and rural areas of the United States. The families were recruited shortly after the birth of a child in 1991. Mothers reported how many hours the children were exposed to television-defined as "being awake in the room when the television is on"-on two specific weekdays and two specific weekend days when their children were aged 36 months. Researchers recorded the children's height and weight during visits at age 36 and 54 months, and calculated body mass index (BMI) by dividing weight in kilograms by the square of height in meters. If a child had a BMI that was greater than or equal to the 95th percentile for children of their age and sex, he or she was considered overweight.

Fewer than one-third (31.7 percent, 322 children) were exposed to less than two hours of television per day, while 694 (68.3 percent) were exposed to more than two hours. About 5.5 percent of the children were overweight at the beginning of the study, 5.8 percent at age 36 months and 10 percent at age 54 months. Children exposed to more than two hours of television per day were more likely than those exposed to less than two hours to be overweight at age 36 months and age 54 months. The association between excessive television viewing and weight at age 36 months remained when the researchers considered other factors, including the mother's age, educational level and marital status.

Television exposure could contribute to increased weight in many ways, including through the advertising of unhealthy foods or the tendency of children to snack while watching TV, the authors suggest. Television's effect appears powerful even when children aren't giving it their full attention. "Our findings suggest that exposing children to TV even as 'background noise' while they engage in other activities may increase overweight risk," they conclude. "It may be equally relevant in clinical practice to ask parents how often the child is in the presence of a TV that is 'on' as it is to ask how much time the child spends 'watching TV'."

Prevalence Of Overweight Children, Teens And Men In U.S. Continues To Rise

Wed, 05 Apr 2006 19:01:00 PST

( from http://www.rxpgnews.com ) The prevalence of overweight and obesity among children and adolescents and obesity among men increased significantly between 1999 and 2004, according to a study in the April 5 issue of JAMA.

Obesity continues to be a leading public health concern in the United States. Between 1980 and 2002, obesity prevalence doubled in adults aged 20 years or older and overweight prevalence tripled in children and adolescents aged 6 to 19 years, according to background information in the article.

Cynthia L. Ogden, Ph.D., of the Centers for Disease Control and Prevention, Hyattsville, Md., and colleagues examined data on national measurements of weight and height in 2003-2004 and compared these data with estimates from 1999-2000 and 2001-2002 to determine if the overweight trend is continuing. The data consisted of weight and height measurements from 3,958 children and adolescents aged 2 to 19 years and 4,431 adults aged 20 years or older obtained in 2003-2004 as part of the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the U.S. population. Overweight among children and adolescents was defined as at or above the 95th percentile of the sex-specific body mass index (BMI) for age growth charts based on data collected between 1963 and 1994. Body mass index is calculated as weight in kilograms divided by the square of height in meters. Obesity among adults was defined as a BMI of 30 or higher; extreme obesity was defined as a BMI of 40 or higher.

The researchers found that 17.1 percent of children and adolescents aged 2 to 19 years were overweight and 32.2 percent of adults aged 20 years or older were obese in 2003-2004. The prevalence of extreme obesity among adults was 4.8 percent. There was a significant increase in the prevalence of overweight in female children and adolescents from 13.8 percent in 1999-2000 to 16 percent in 2003-2004. There was also an increase in the prevalence of overweight in male children and adolescents from 14.0 percent to 18.2 percent.

Among men, the prevalence of obesity increased significantly between 1999-2000 (27.5 percent) and 2003-2004 (31.1 percent). Among women, no significant increase in obesity was observed between 1999-2000 (33.4 percent) and 2003-2004 (33.2 percent). The prevalence of extreme obesity in 2003-2004 was 2.8 percent in men and 6.9 percent in women.

In 2003-2004, significant differences in obesity prevalence remained by race/ethnicity and by age. Approximately 30 percent of non-Hispanic white adults were obese as were 45 percent of non-Hispanic black adults and 36.8 percent of Mexican Americans. Among adults aged 20 to 39 years, 28.5 percent were obese while 36.8 percent of adults aged 40 to 59 years and 31.0 percent of those aged 60 years or older were obese in 2003-2004.

There is little indication that the prevalence is decreasing in any subgroup of the population. These prevalence estimates, based on a 6-year period (1999-2004), suggest that the increases in body weight may be leveling off in women, the authors write.

Adolescent Dieting May Predict Obesity and Eating Disorders

Wed, 05 Apr 2006 13:45:00 PST

( from http://www.rxpgnews.com ) Dieting and "unhealthful weight-control behaviors" among adolescents can predict the development of eating disorders in years to come, according to researchers at the University of Minnesota.

In a follow-up to a 1999 study of more than 2,500 junior high and high school students, the researchers found that students who engaged in unhealthy weight-control behaviors such as dieting and binge eating were three times more likely five years later to be overweight than adolescents who did not engage in those behaviors. They were also at significantly increased risk for binge eating with loss of control as well as extreme weight-control behaviors such as self-induced vomiting and the use of diet pills, laxatives and diuretics.

"Findings from this study suggest that dieting, and particularly unhealthful weight control, is either causing weight gain, disordered eating or eating disorders; serving as an early marker for the development of these later problems or is associated with some other unknown variable that is leading to these problems," the researchers write. They add that "unknown variables" may include personality characteristics or genetic factors.

"None of the behaviors being used by adolescents (in 1999) for weight-control purposes predicted weight loss," the researchers write.

"Of greater concern were the negative outcomes associated with dieting and the use of unhealthful weight-control behaviors, including significant weight gain. These findings demonstrate that these behaviors should not be viewed as innocuous and should be addressed in primary and secondary prevention efforts."

A simple blood test to detect rare lysosomal storage disorders disorders

Thu, 30 Mar 2006 15:12:00 PST

( from http://www.rxpgnews.com ) Scientists have devised a simple blood test that they say can detect rare disorders.

Frantiek Turecek and other researchers at the University of Washington in Seattle devised the test for progressive genetic diseases known as 'lysosomal storage disorders', reported the online edition of Nature.

These disorders can cause symptoms ranging from gross enlargement of the liver to mental retardation. Some 40-50 of the disorders are known, and in total they affect one in 5,000 people. Gaucher disease, one of the more common afflictions, affects a little more than one in 1,000 Ashkenazi Jews.

The researchers say their screening method can now detect seven of these diseases. Cambridge-based company Genzyme, which sells treatments for three of the diseases, hopes to see the screen made a routine part of newborn testing.

Lysosomes are small compartments within cells that help to recycle waste cellular material within the body. Enzymes within the lysosomes do this job by breaking up waste materials into smaller pieces.

If one of these enzymes is not functioning, usually because of a problem in the gene that codes for it, then the breakdown stops and half-digested matter clogs up the cell with disastrous consequences.

Newborn babies with these diseases can be healthy, because there has been little time for this material to build up. Blood tests are available for cases where lysosomal diseases are suspected.

But doctors are keen to find a way to diagnose the disorders before problems begin so that treatment, if it exists for the specific condition, can start early.

'Once you get damage, there is no way back,' say Turecek. 'Either you get going on treatment early, or you can die. And it is not a good death.'

The methodology by them isn't very complicated and should be quite cheap, researchers said. The group estimates that a single machine should be able to process 85,000 screenings a year.

This would be enough to cover the state of Washington, for example. A screening which could look for up to 20 different enzymes at a time should cost as little as five cents after the purchase of a suitable mass spectrometer, they say.

Lipin is a key fat-regulating enzyme

Tue, 21 Mar 2006 02:35:00 PST

( from http://www.rxpgnews.com ) Rutgers researchers have identified a gene and the molecular function of its protein product that provides an important clue to further understanding obesity and may point the way to new drugs to control fat metabolism.

The scientists found that the human protein known as lipin is a key fat-regulating enzyme. "Lipin activity may be an important pharmaceutical target for the control of body fat in humans, treating conditions that range from obesity to the loss of fat beneath the skin, as seen in HIV patients, " said George M. Carman, a professor in Rutgers' department of food science.

In a paper published online by the Journal of Biological Chemistry (print version, April 7), Carman and his research team at Rutgers' Cook College describe their scientific detective work, moving from clue to clue in a series of logical connections to reach their discoveries.

Previous studies with mice showed that a lack of lipin causes a loss of body fat, whereas an excess of lipin promotes extra body fat. So researchers knew that lipin was involved in fat metabolism; they just didn't know how.

The Carman team's first revelation came with the discovery that lipin is an enzyme (phosphatidic acid phosphatase or PAP), a protein catalyst that is required for the formation of fats triglycerides, specifically.

The breakthrough for Carman's group grew out of work with ordinary baker's yeast; a simple single cell organism. "We isolated the PAP enzyme from yeast that corresponds in form to lipin in mammals and showed that yeast cells lacking the enzyme exhibited a 90 percent reduction in the yeast's version of fat loss," Carman said.

The group worked out the sequence of the amino acids that make up the PAP enzyme, allowing them to backtrack along the path to its origin the gene that coded it linking the enzyme to the yeast gene PAH1 that made it. Carman and his group went on to confirm the link by introducing the yeast gene into bacteria, with similar results.

The researchers showed that the enzyme encoded by the PAH1 gene looks and acts very much like the lipin found in mammals. The yeast PAP enzyme shares a high resemblance to the lipin protein in mammals so they logically deduced the link between PAP enzyme function and lipin.

"These findings are of major importance to the AIDS community as well as to those concerned with the obesity epidemic," said Jean Chin, a program director at the National Institute of General Medical Sciences (NIGMS), the part of the National Institutes of Health that funded the research. Carman's research is also supported by the New Jersey Agricultural Experiment Station.

Fat fuels inflammation killer

Wed, 08 Mar 2006 21:59:00 PST

( from http://www.rxpgnews.com ) New research by the University of Warwick's Warwick Medical School shows that the biggest health threat to fat and obese people isn't the fat itself but the fact that the fat fuels a killer inflammation response in people.

The research published in the International Journal of Obesity on Tuesday 7th March shows that inflammation is a crucial and dangerous step in the development of obesity.

Warwick Medical School researchers Professor F P Cappuccio and Dr M A Miller have studied a large group of people, belonging to 3 different ethnic groups, and have measured a variety of markers of inflammatory activation and related these to measures of obesity or fatness such as body mass index (BMI) and waist-hip ratio (WHR). The study clearly showed that the levels of sE-selectin, a marker of inflammation produced by artery vessel walls, are strongly associated with measures of obesity, and in particular with the amount of fat around the waist. The research found that every 2% increase in sE-selectin led to the increase of 1 unit in Body Mass Index and 0.01 units in Waist - Hip Ratios.

This inflammation can directly trigger thrombosis, heart disease, strokes and diabetes.

There have been suggestions from earlier studies of small patient groups that inflammation had this importance but this is the first ever study to find these results across an unselected population of healthy subjects which covered both sexes and three ethnic groups (White, South Asian and people of African origin)

Dr Miller and Professor Cappuccio said:

"This study highlights the importance of the activation of the endothelium, the inner layer of the artery vessel wall, in the metabolic processes leading to obesity and cardiovascular disease". "This observation opens opportunities to develop new treatments that deal directly with inflammation either through diet or drugs".

Dairy is not associated with weight gain - Research

Wed, 08 Mar 2006 21:55:00 PST

( from http://www.rxpgnews.com ) Calcium intake was not associated with weight gain in men over a 12-year period, according to a new study published in the American Journal of Clinical Nutrition1. The study included more than 19,000 healthy men aged 40-75 years who were enrolled in the Health Professionals Follow-up Study. The researchers evaluated the relationship between total calcium intake from diet and supplements and changes in body weight based on self reported weight at the beginning and end of the 12-year study period. Study participants followed their normal diets, not calorie-restricted diets.

This research is consistent with the 2005 Dietary Guidelines for Americans which recommend 3 servings of low-fat dairy foods each day and recognize that intake of dairy foods does not contribute to extra weight gain.

In addition to research that demonstrates dairy foods do not contribute to extra weight gain, dozens of studies provide compelling evidence that consuming 3 servings a day of milk, cheese and yogurt as part of a reduced-calorie weight loss plan may help adults achieve better results than just cutting calories with little or no dairy, according to Greg Miller, PhD, executive vice president, National Dairy Council.

The current body of evidence includes randomized clinical trials (considered the "gold standard" of science), observational, animal and cellular studies conducted by leading research institutions throughout the country. This intriguing connection also is being studied worldwide with positive results reported in Denmark, Greece, Italy and other countries.

"The good news for the public is that you can follow the MyPyramid recommendation for 3 servings of dairy foods each day and get the nutrition benefits without concern of extra weight gain," Miller said. "If you're cutting calories to lose weight, it's important to get your 3 servings of dairy foods each day for good health and to enhance your weight loss efforts."

Though more research is needed to fully understand the relationship between dairy and weight, experts suggest this emerging role for dairy foods is another good reason for people to meet current Dietary Guidelines for Americans of 3 servings a day of low-fat or fat-free milk, yogurt or cheese.

Additional benefits to dairy consumption noted by this study include findings that dairy eaters were less likely to have high blood pressure or elevated cholesterol levels and tended to have a higher intake of cereal fiber and vitamin D.

The authors of this observational study acknowledge that the results regarding calcium and weight gain are not conclusive, noting that "whether calcium supplementation or increased dairy intake is beneficial in preventing weight gain needs to be further studied in long-term randomized trials."

Studies published in Obesity Research showed that adults on a reduced-calorie diet who consumed 3 servings of milk, cheese or yogurt each day lost significantly more weight and more body fat than those who just cut calories and consumed little or no dairy2,3,4.

Numerous observational studies exploring dietary intake patterns and body weight in various population groups have suggested that getting adequate amounts of dairy not only promotes an overall healthy diet, but may also promote a healthy weight.

Bottle-feeding could make infants obese

Wed, 08 Mar 2006 21:51:00 PST

( from http://www.rxpgnews.com ) Bottle-feeding could make your baby obese later in life, finds a University of Bristol study.

Researchers said babies feeding on formula milk who were weaned on to solid foods too early were heavier than expected by the age of five, putting them at an increased risk of obesity as they grow older, reported the online edition of Daily Mail.

The feeding habits of 881 babies at four months were examined and compared to their weight gain later in childhood by the researchers.

The study, published in the US journal Paediatrics, found that babies drinking formula milk rather than breast milk took in more calories and experienced weight gain at a crucial stage of growth.

"It seems that breast-fed infants are better able to regulate their energy intake than formula-fed infants, nutritionist doctor Pauline Emmett stated.

"It could be because parents feeding formula milk make sure that the baby finishes the bottle and do not necessarily reduce the quantity offered once weaning is established."

She added that excessive weight gain might lead to increased risk of obesity later in life.

"While there are obvious benefits in avoiding poor growth, excessive weight gain during infancy is also a problem."

Obese drivers face greater risk of crash deaths

Mon, 06 Mar 2006 17:22:00 PST

( from http://www.rxpgnews.com ) Male drivers who are obese are more likely to die in a car crash, suggests a US study.

Researchers of the Medical College of Wisconsin said the deaths could be due to the drivers' greater momentum in a crash and because of the effect obesity has on the body's ability to recover.

The researchers looked at information on 22,000 people from a nationwide crash data collection programme sponsored by the US Department of Transportation.

They found that drivers who had a body mass index that was either higher than 35 or lower than 22 had a "significantly increased risk of death" compared to those with an intermediate body mass index (BMI), reported the online edition of BBC News.

While the fatality rate for motor vehicle crashes was 0.87 percent for male drivers, it was 0.43 percent for women drivers, the researchers found.

Adventure Therapy effective in maintaining weight-loss

Wed, 01 Mar 2006 17:33:00 PST

( from http://www.rxpgnews.com ) Some overweight teens may have new hope for shedding pounds. A new study suggests that weight-loss programs that encourage peer-support, and focus on building confidence through challenges are effective in helping some adolescents lose weight. This is the finding of a research paper appearing in the January 2005 issue of the International Journal of Obesity by researchers at the Bradley Hasbro Children's Research Center (BHCRC) and The Miriam Hospital.

"Since weight gain in adolescence has been associated with a number of health problems in adulthood, we wanted to find a program that could offer teens an effective weight-loss strategy," says lead author Elissa Jelalian, PhD, a child psychologist with the BHCRC and Brown Medical School.

Seventy-six overweight adolescents (ages 13 to 16) were randomly assigned to one of two treatment plans for 16 weeks: cognitive-behavioral group treatment with Adventure Therapy based on Outward Bound (an educational program that promotes adventure and peer-building activities), or cognitive-behavioral group treatment in conjunction with aerobic exercise.

"We found that the older teens in our sample lost more weight through the Adventure Therapy regimen, and many kept it off at the 10 month follow-up," says Jelalian.

While average weight loss was similar for both groups, the authors saw significant differences between the groups six months after completion of the active intervention. Over twice as many adolescents in the Adventure Therapy group maintained their weight loss. Even more impressive, they found that older adolescents in the adventure therapy group demonstrated more than four times the weight loss of their counterparts in the aerobics group at follow-up.

"This study supports the idea that at ages 15 and 16, adolescents may benefit significantly from peer support. The Adventure Therapy model embraces positive peer encouragement which is why it's so effective," says Jelalian.

Rather than participating in a supervised exercise session together, adolescents assigned to the Adventure Therapy group were asked to work together in cooperative games, trust-building exercises, and problem solving challenges. The final challenge was for adolescents to participate in a ropes course.

Obesity in children and adolescents is a significant public health concern, the authors write. Data from the most recent National Health and Nutrition Examination Survey data (NHANES 1999-2000) indicate that approximately 15 percent of children and adolescents are overweight. The recent Surgeon General's "Call to Action" describes overweight and obesity as a public health epidemic, with specific focus on the impact of overweight for children and adolescents.

"The obesity epidemic our country is facing has created a tremendous need for innovative, effective weight loss strategies for overweight teens," says co-author Elizabeth Lloyd-Richardson, PhD, psychologist at The Miriam Hospital and Brown Medical School. The rise in prevalence of pediatric obesity has been associated with a rise in the diagnosis of non-insulin-dependent diabetes, as well as risk factors for heart disease. Weight increases during adolescence have also been associated with fasting insulin, HDL-cholesterol, and systolic blood pressure in young adulthood.

"Evidence suggests that losing even small amounts of weight (5 to 10 percent of body weight) can have a significant impact on health," says co-author Rena Wing, PhD, director of the Weight Control and Diabetes Research Center at The Miriam Hospital and Brown Medical School.

Furthermore, childhood and adolescent obesity are significant predictors of overweight status in adulthood and pose a risk factor for adult morbidity and mortality, particularly for males, the authors write.

Obesity increases the risk of cancers

Tue, 28 Feb 2006 21:11:00 PST

( from http://www.rxpgnews.com ) Obesity increases the risk of contracting cancer, states Dr. Javier Salvador, Director of the Department of Endocrinology and Nutrition at the University Hospital of the University of Navarra.

Overweight has become a worldwide epidemic, not only in industrialised countries, but also in developing ones where problems of malnutrition go hand in glove with high percentages of obesity. The rates are currently rising at an alarming pace. In Spain some 15% of the population suffer from obesity and 54% from an excess of weight. Rates are going up because of the imbalance between ingestion and calorie consumption - due both to the growth and proliferation of unhealthy eating habits and an increase in sedentary life habits and styles.

One of the main problems in Western society is the rise in infant obesity the incidence of which has now reached that of obesity amongst adults. It is known that a very high proportion of these children will be obese when they become adults. Treatment is complicated and so we have to take action on prevention and on encouraging healthy lifestyles and habits in the home, at school and so on.

Clinical repercussion

Overweight produces significant changes in health, particularly those of a cardiovascular nature such as high arterial (blood) pressure, cardiopathy and ischemia; but also problems of a metabolic nature such as diabetes type 2 and changes in blood fat, apnea during sleep, alterations in the joints, and so on. Obesity is also involved in changes in hepatic function as a consequence of the infiltration of fat, the liver deteriorates and may end up with hepatic cirrhosis.

Society at large is aware that obesity is damaging in these ways to our health. What has not been known to date is that it is associated with certain cancers. This is important, for example, for women with a family history of breast cancer obese members of these families are more likely to contract the disease.

Apart from clinical pathologies overweight causes psychological problems of self-esteem, symptoms of depression, anxiety, and so on. Thus, dealing with and treating all these means high health costs.

Chocolate milk may help athletes

Sun, 26 Feb 2006 17:06:00 PST

( from http://www.rxpgnews.com ) Chocolate milk may be as good - or better - than common sports drinks like Gatorade or Endurox R4 at helping athletes recover from strenuous exercise, says a new study.

Intense endurance exercise reduces supply of stored glucose or glycogen, a key source of fuel for exercise, to the muscles.

To maximise glycogen replacement, sportsmen use to take a serving of carbohydrates within 30 minutes after a long and vigorous workout.

Common sports drinks such as Gatorade supply those carbohydrates, as well as fluids and electrolytes lost through sweat. More recent research suggests that adding protein to the mix may further hasten recovery.

The new study, published in the International Journal of Sport Nutrition and Exercise Metabolism counter the notion that high-tech, expensive supplements are better than whole foods when it comes to athletic performance, it said.

A team of researchers led by Joel M. Stager of Indiana University found that milk contains key nutrients, such as calcium and vitamin D, in quantities that sports drinks can't match.

In the study, nine male cyclists rode until their muscles were depleted of energy, then rested four hours and biked again until exhaustion.

During the rest period, the cyclists drank low-fat chocolate milk, Gatorade, or another sports drinks Endurox R4. During a second round of exercise, the cyclists who drank the chocolate milk were able to bike about 50 percent longer than those who drank Endurox, and about as long as those who drank the Gatorade.

The findings suggest that chocolate milk has an optimal ratio of carbohydrates to protein to help refuel tired muscles, Stager said.

No risk reduction from reducing total dietary fat - Women's Health Initiative (WHI) study

Wed, 08 Feb 2006 11:15:00 PST

( from http://www.rxpgnews.com ) Despite findings being announced this week that a low-fat diet introduced in the middle-age years didn't reduce the risk of breast cancer, heart disease, stroke or colon cancer, one of the researchers says people still need to focus on the types of fat they eat. The national diet study of almost 50,000 healthy postmenopausal women was part of the massive Women's Health Initiative (WHI) study.

The hypothesis that low-fat diets could help reduce the risk of certain diseases had been assumed, but never tested. But, do the findings mean that what we eat doesn't matter?

"Nutrition knowledge has progressed dramatically since the study began," said Mara Vitolins, Dr.Ph., associate professor of public health sciences at Wake Forest University Baptist Medical Center. "Today, we know that reducing total fat may not be enough we need to focus on the types of fat we eat."

Vitolins, a registered dietician, is an author on the three papers that report the results in the Feb. 8 edition of the Journal of the American Medical Association. Wake Forest was a Vanguard Center, one of 16 university sites chosen to launch the WHI.

The study compared a group of women who followed their normal eating patterns with a group who followed a study diet designed to reduce total fat. At the end of the first year, the low-fat diet group was consuming about 24 percent of calories from fat, compared to 35 percent in the normal-diet group.

At the end of the study's sixth year, the low-fat diet group consumed about 29 percent of calories from fat, compared to 37 percent in the normal-diet group. The low-fat diet group also increased their consumption of vegetables, fruits and grains.

Researchers found no difference between the two groups in terms of risk of breast cancer, colon cancer, heart disease or stroke.

Vitolins said one explanation for the results is that the low-fat diet was designed to reduce total fat and didn't make a distinction between good fats, such as those found in nuts, fish, and vegetables oils, and bad fats, such as the saturated fat in meats and the trans fat used in baked goods and potato chips.

"The study was testing the belief that lowering total fat would reduce the risk of cancer," said Vitolins. "Since the study began, we've learned a lot more about how the types of fats we consume make a difference."

Vitolins and others said the study's findings should not change recommendations for staying healthy.

"The results of this study do not change established recommendations on disease prevention," said National Heart, Lung, and Blood Institute Director Elizabeth G. Nabel, M.D., in an NIH press release. "Women should continue to get regular mammograms and screenings for colorectal cancer, and work with their doctors to reduce their risks for heart disease including following a diet low in saturated fat, trans fat and cholesterol."

Current dietary guidelines call for keeping saturated fats to less than 10 percent of calories, with most fats coming from fish, nuts and vegetable oils. They also call for limiting levels of trans fat. Vitolins said that only recently has trans fat become recognized as harmful it must now be listed on food labels.

Vitolins also said it's important to remember that participants began the low-fat diet later in life. Women were 50 to 79 years old when the study began and were followed for an average of 8.1 years.

"Our diets start when we are born and it makes sense that what you eat over a lifetime will make a difference," she said.

About 3,300 women in the Piedmont Triad were participants in the Women's Health Initiative, according to local principal investigator Denise E. Bonds, M.D., M.P.H., assistant professor of public health sciences at Wake Forest University Baptist Medical Center. Of those, 988 participated in the diet study, which was one of three WHI trials. The other trials evaluated hormone therapy and the effects of calcium and vitamin D on prevention of osteoporosis-related bone fractures and colon cancer.

Nationally, the WHI enrolled 157,000 women between 50 and 79 years old at 40 clinical centers, making it the largest clinical trial ever undertaken in the United States.

Whole grains in diet reduce risk of metabolic syndrome

Tue, 07 Feb 2006 15:27:00 PST

( from http://www.rxpgnews.com ) With the recent revision of the Food Guide Pyramid, the Dietary Guidelines for Americans have for the first time provided the public with a quantitative recommendation for whole-grain intake. In a study published in the January issue of American Journal of Clinical Nutrition, researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (HNRCA) found that consuming a diet rich in whole-grain foods may lower an elderly person's risk for cardiovascular disease and reduce the onset of metabolic syndrome. Metabolic syndrome, which is a collection of risk factors, puts people at an increased risk of cardiovascular disease and type 2 diabetes.

The study, a collaborative effort that included Paul Jacques, DSc, director of the Nutritional Epidemiology Program at the HNRCA, Nicola McKeown, PhD, scientist in the same program, and others, examined the relationship between whole-grain intake and cardiovascular disease risk factors, metabolic syndrome, and the incidence of death due to cardiovascular disease in the elderly.

"Previous studies have found a link between whole-grain intake and reduced risk of metabolic syndrome in middle-aged populations. What's unique about our study," says McKeown, "is that we went back to data that was collected 20 years ago, using diet records that captured food intake, and found that whole-grain foods had a subsequent benefit in the elderly." The ability of researchers to differentiate whole grains from refined grains more accurately through the use of diet records is a major advantage when assessing dietary intake. "In past studies," states McKeown, "fixed food categories have made it difficult to accurately separate whole and refined grains for some food items â such as breads."

According to Jacques, who is also a professor at the Friedman School of Nutrition Science and Policy at Tufts, "consuming a high whole-grain diet is likely to have positive metabolic effects in elderly individuals, who are prone to greater insulin resistance and impaired glucose tolerance."

McKeown and Jacques found that, indeed, as whole-grain intake increased, fasting blood sugar levels were lower in these subjects. Refined grain intake, on the other hand, was associated with higher fasting blood sugar levels. Elevated fasting blood sugar levels can indicate impaired glucose tolerance and the presence of diabetes. In addition, people who consumed high amounts of refined grains had twice the risk of having metabolic syndrome than those people who consumed the fewest servings of refined grains.

"It is important to note," cautions McKeown, "that the subjects in the study were not a representative sample of the elderly, so we do not know the implications of applying these results to other populations. Based on the research, whole-grain intake is one modifiable dietary risk factor that may lead to substantial health benefits at the population level, even among an older population. Older adults should be encouraged to increase their daily intake of whole grain foods to three or more servings a day by substituting whole grains for refined grains."

Babies of obese mothers have higher risk of some birth defects

Sun, 05 Feb 2006 00:30:00 PST

( from http://www.rxpgnews.com ) Compared to normal-weight women, overweight and obese women suffer more pregnancy complications and their babies have more medical problems at birth, according to a position paper of the Public Affairs Committee of the Teratology Society.

Obesity afflicts men and women of all ages across the United States and it is on the rise. Among women aged 20 to 39, more than half are overweight and nearly a third are obese, according to the National Health and Nutrition Examination Survey.

Obese women face increased risk of infertility and problems during pregnancy, including hypertension, gestational diabetes and thromboembolic events and are more likely to need a cesarean section. One French study found that overweight women had higher prenatal medical costs, and spent more time in the hospital recovering from childbirth.

In addition, the babies of obese mothers are more likely to be admitted to neonatal intensive care units. They also have a higher incidence of neural tube defects. "The literature suggests that compared to normal weight women, women whose body mass index (BMI) is greater than or equal to 30 have approximately double the risk of having an affected child," according to the Public Affairs Committee. The increased risk cannot be explained by folic acid intake, or by maternal diabetes.

The relationship between obesity and other birth defects remains unclear, according to the paper, because limited data is available, though some studies suggest a correlation.

"The Public Affairs Committee views obesity as a pregnancy risk factor and supports the public health initiatives identified by the FDA and the research initiatives identified by the NIH," the Committee writes. The national agencies are addressing the problem of obesity and acknowledging pregnancy as an important subject of further study.

The paper suggests that weight reduction efforts should be made well before conception is attempted, and dieters should avoid pregnancy. "Adequate nutrition is important for pregnant women and women planning pregnancy," the paper says. The committee recommends that clinicians counsel pregnant women about appropriate caloric intake and exercise.

While weight reduction surgery can improve the health and also the fertility of overweight women, the committee does not make a recommendation regarding surgery. They note that some recent reports have shown that women with gastric banding can have normal pregnancies and better pregnancy outcomes than obese women who do not have the surgery.

"Because some weight loss procedures can result in nutritional deficiencies, it appears reasonable to recommend that pregnancy be delayed until surgery-related weight loss has stabilized," writes the Committee.

Lastly, the paper recommends that all parents be educated about appropriate childhood nutrition, including the value of breastfeeding, which has been shown to have a protective effect against childhood obesity. "Prevention of childhood obesity is expected to be important in the prevention of obesity during the reproductive years," the paper concludes.

FDA questions on long term benefits of Orlistat

Sat, 21 Jan 2006 17:13:00 PST

( from http://www.rxpgnews.com ) Efficacy concerns surrounding GlaxoSmithKline's orlistat may prove to be a bigger hurdle to overcome than safety or self-selection issues as the firm pursues an Rx-to-OTC switch of the drug.

Although the proposed OTC dose of 60 mg shows statistically significant weight loss, 'there is no evidence presented that a modest, transient weight loss due to orlistat will afford any long-term clinical benefit through either a change in behavior or a reduced risk of serious clinical diseases manifested by being overweight,' an FDA review of studies on the drug finds.

The FDA documents, released Jan. 20, question whether GSK's proposed six-month treatment submitted under the trade name Alli would be beneficial for a 'chronic' condition such as obesity.

The documents were released in advance of a Jan. 23 review of the switch proposal by the agency's Nonprescription Drugs and Endocrinologic & Metabolic Drugs advisory committees.

GSK filed the orlistat switch application in June after purchasing licensing rights to the drug's OTC version from Roche in July 2004.

According to the agency, drug treatment for chronic conditions 'must be maintained long-term or chronically' to result in clinical benefit.

"It is difficult to define the clinical benefits of short-term treatment with orlistat," FDA states.

"Although not studied by the sponsor, it is well known that once weight-loss treatment is stopped, lost weight is quickly regained and improvements in co-morbidities become undone."

Efficacy of orlistat use in �mildly overweight� people with a Body Mass Index of 25-28 also was questioned in the agency's review.

Comparing studies conducted for orlistat's Rx approval and proposed switch "raise[s] the possibility that orlistat may be less effective in mildly overweight individuals than in obese subjects," the agency states.

The prescription NDA study was conducted in people with a BMI of at least 28. Among the subjects, a 5% or greater weight loss was achieved by 42% of those who took a 60 mg dose, 45% of subjects who took a 120 mg dose and 23% of those taking placebo.

In a more recent study conducted to support an orlistat switch, participants had a BMI of 25-28. A 5% or more weight loss was achieved in 36% of those taking the 60 mg dose and 28% taking placebo.

The difficulty in determining the benefits of short-term treatment is "further complicated," the agency states, because "some evidence suggests that the overweight BMI range of 25- <30 is not associated with increased mortality

Chronic stress at work and metabolic syndrome

Fri, 20 Jan 2006 15:19:00 PST

( from http://www.rxpgnews.com ) Stress at work is an important risk factor for the development of heart disease and diabetes, finds a study published online by the BMJ today.

Stress at work has been linked with heart disease, but the biological processes were unclear. This study provides new evidence for the biological plausibility of the link between work stress and heart disease.

Researchers examined the association between work stress and the metabolic syndrome (a cluster of factors that increases the risk of heart disease and type 2 diabetes) in 10,308 British civil servants aged between 35 and 55, over a 14 year period.

Work stress was measured on four occasions between 1985 and 1999. Components of the metabolic syndrome, such as obesity, high blood pressure, and high cholesterol levels, were measured between 1997 and 1999. Social position and health damaging behaviours, such as smoking, heavy alcohol consumption, and lack of exercise, were also recorded.

A dose-response relation was found between exposure to job stress and the metabolic syndrome, even after adjusting for other risk factors. For example, men with chronic work stress were nearly twice as likely to develop the syndrome than those with no exposure to work stress. Women with chronic work stress were also more likely to have the syndrome, but they formed a small group.

Both men and women from lower employment grades were more likely to have the syndrome, confirming previous reports that the syndrome has a social gradient.

The association between the metabolic syndrome and exposure to health damaging behaviours was stronger among men than women. Poor diet (no fruit and vegetable consumption), smoking, heavy alcohol consumption, and physical inactivity were all associated with higher odds of the syndrome.

Despite some study limitations, a dose-response relation exists between exposure to work stress and the metabolic syndrome, even after other risk factors are taken into account, say the authors.

One possible explanation is that prolonged exposure to work stress may affect the nervous system. Alternatively, chronic stress may reduce biological resilience and thus disturb the bodys physiological balance (homoeostasis).

This study provides evidence for the biological plausibility of psychosocial stress mechanisms linking stressors from everyday life with heart disease, they conclude.

Fat overload kills mammalian cells

Thu, 19 Jan 2006 15:46:00 PST

( from http://www.rxpgnews.com ) Investigating the harmful health effects of excess fat, researchers at Washington University School of Medicine in St. Louis have identified a protein that triggers death in mammalian cells overloaded with saturated fat.

The internal "skeleton" (in red) of cells is altered by exposure to high fat.

When the researchers halted production of this protein, called EF1A-1, the cells were able to thrive in ordinarily damaging amounts of the saturated fat palmitate, a fat abundant in Western diets. At the same concentration of palmitate, normal cells still producing EF1A-1 rapidly died. The study will be published in the February 2006 issue of Molecular Biology of the Cell.

"When lipids (fats) accumulate in tissues other than adipose tissue, cellular dysfunction or cell death results," says senior author Jean Schaffer, M.D., associate professor of medicine and of molecular biology and pharmacology. "For example, preliminary studies on animals suggest that the accumulation of fat in the pancreas contributes to the development of diabetes, and accumulation of lipids in skeletal muscle of leads to insulin resistance."

Other studies have linked the genesis of heart failure to fat-induced cell dysfunction and cell death in the heart. "As physicians our primary focus in diabetic patients is on glucose control," says Schaffer, a member of the Center for Cardiovascular Research at the School of Medicine and a cardiologist at Barnes-Jewish Hospital. "But it appears we should also be more aggressive with respect to lowering lipids such as triglycerides and fatty acids."

With the discovery of EF1A-1's role, this study is the first to identify a critical step in the pathway that leads from high cellular fat to cell death, according to Schaffer. EF1A-1 is an extremely abundant protein with several diverse functions within cells, including protein synthesis and maintenance of the cytoskeleton, the cell's internal support structure.

In mammalian cells grown in culture, the researchers saw that EF1A-1 and the fat palmitate work hand in hand: the presence of EF1A-1 dictated sensitivity to palmitate-induced cell death, and palmitate caused a rapid increase of the amount of EF1A-1 produced.

Schaffer's laboratory earlier had developed a transgenic mouse that accumulates fat in its heart muscle cells resulting in the death of cells, heart failure and premature death. They found that EF1A-1 was increased nearly three-fold in the hearts of these animals.

Removal of EF1A-1 protected cells from palmitate-induced death, and its absence allowed cells to withstand assault by highly reactive oxygen molecules. According to study authors, this indicates that EF1A-1 probably contributes to cell death from oxidative stress, which is known to stem from high lipid levels. Cytoskeletal changes seen in cells missing EF1A-1 suggested to the researchers that EF1A-1's cytoskeletal role also is important in cell death resulting from fat overload.

"Cells have a lot of mechanisms for incorporating fatty acids into storage forms, for metabolizing them or for using them in cellular membranes," Schaffer says. "But saturated fats like palmitate are poorly stored in the tiny fat droplets normally found in most cells and therefore are more likely to enter into pathways that lead to cell death such as the one in which EF1A-1 is involved."

In the process of identifying the role of EF1A-1, the lab members uncovered other proteins implicated in the toxicity of excess fats. They are now investigating each to find out what part it plays.

Future investigations by Schaffer's research team will study the EF1A-1 protein to see whether fatty molecules directly alter the protein, or if they cause it to relocate within the cell.

Teen Weight Control Behaviour May Reflect Mothers' Attitudes On Weight

Thu, 08 Dec 2005 15:14:00 PST

( from http://www.rxpgnews.com ) Teenagers are more likely to think about wanting to be thin, and to be frequent dieters, if they accurately perceive that being thin is important to their mothers, according to a study in the December issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

The association between body weight of children and their parents is known to be affected by genetic and cultural factors. However, less is known about the relationship between the weight concerns and weight control practices of parents and their children. Mothers are thought to play a role in the transmission of cultural values about body weight and shape. Studies show that girls whose mothers diet and are concerned with their weight and shape are more likely than their peers to develop unhealthy weight control practices, according to background information in the article.

Alison E. Field, Sc.D., of Harvard-affiliated Brigham and Womens Hospital and Childrens Hospital, Boston, and colleagues assessed the association between weight concerns and weight control practices of adolescents and their mothers. The authors conducted a cross-sectional study of 5,331 girls and 3,881 boys, with a mean [average] age of 14.9 years (range, 11.8 to 18.4 years), and their mothers. Participants were included in the analysis if both the adolescent and his or her mother returned a questionnaire mailed in 1999 and provided information on weight, height, and weight concerns.

Weight concerns were more common among girls, with 33 percent of girls and 8 percent of boys thinking frequently about wanting to be thinner. Approximately 54 percent of mothers reported that they thought about wanting to be thinner a lot or always, and 22 percent reported frequently attempting to lose weight during the past year. Also, 0.4 percent of girls and 3.7 percent of boys accurately perceived that their weight was important to their mother. Eight percent of girls had frequently dieted during the past year.

Although few adolescents accurately perceived that their weight was important to their mother, adolescent boys and adolescent girls who accurately perceived that their weight was important to their mother were more likely to think frequently about wanting to be thinner and to frequently diet than their peers who accurately perceived that their weight was not important to their mother, the authors report.

Being overweight is associated with many adverse health consequences, so parents are justified in not wanting their adolescents to be overweight, the authors write. However, it is essential to strike a balance between promoting a healthy weight and not placing too much emphasis on the importance of weight.

Parents should be encouraged to be role models in incorporating physical activity and healthy nutrition into everyday lifestyle patterns, rather than implementing them as weight control strategies, they conclude. In addition, it would be advisable for clinicians who treat overweight and weight-concerned adolescents and young adults to promote physical activity for benefits other than weight control, such as helping to improve self-esteem.

Food Incentives In Middle Schools Associated With Overweight Students

Thu, 08 Dec 2005 15:10:00 PST

( from http://www.rxpgnews.com ) Schoolwide food practices and policies that allow frequent snacking and consumption of foods and beverages high in calories and low in nutrients throughout the school day, and that permit use of food as incentives and rewards, were associated with higher body mass index in middle school students, according to an article in the December issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

Obesity has become one of the more complex and challenging public health issues of this decade, affecting two thirds of adults and almost one third (30 percent) of children according to background information in the article. School environmental factors have been implicated in the rising childhood obesity rates. A la carte and vending programs that sell foods and beverages high in calories and low in nutrients are pervasive in schools, and other school food practices that may contribute to childhood obesity, such as fundraising and student incentives, are also documented.

Martha Y. Kubik, Ph.D., R.N., and colleagues from the University of Minnesota, Minneapolis, examined data from sixteen middle schools and their eighth-grade students (n = 3,088) to investigate the association between body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) in young adolescents and schoolwide food practices. BMI was calculated from students self-reported height and weight. School administrators were interviewed about food-related school policies and practices, schoolwide food use guidelines and school-based health promotion activities. Based on interview answers, a food practice score was determined for each school, higher scores indicating more practices were allowed.

The researchers found that students BMI increased ten percent for every additional food practice permitted in their school. Average BMI of the students was 21. Eight percent of students were classified as overweight, while fifteen percent were categorized as being at risk for overweight. The average number of food practices allowed was three (range, 0 7). Of the seven food practice scale items, the most prevalent was the use of food as incentive and rewards (69 percent) and in classroom fundraising (56 percent). Thirty-one percent of schools allowed food in the classroom, while 38 percent allowed beverages in the classroom. Nineteen percent of schools allowed beverages in hallways, while 31 percent allowed snacks in the hallway.

Food choice at school includes more than the foods and beverages offered as a part of school meal programs, a la carte, and in vending machines. Similarly, opportunities for eating during the school day extend well beyond the school lunchroom and breakfast and lunch, the authors write. Adolescence is a critical period for the development of obesity that persists into adulthood.School nutrition policies that consistently promote and support healthy dietary practices among young adolescents are urgently needed, they conclude.

Low-carb diet better at improving metabolic syndrome

Wed, 16 Nov 2005 19:25:00 PST

( from http://www.rxpgnews.com ) Diabetes and cardiovascular disease associated with it. In an article published today in the open access journal Nutrition & Metabolism, Jeff Volek and Richard Feinman review the literature and show that the features of metabolic syndrome are precisely those that are improved by reducing carbohydrates in the diet. Metabolic syndrome is a cluster of health signs that may occur together and indicate a risk for diabetes, stroke and heart disease. The markers of metabolic syndrome - high blood pressure, low HDL levels, high triglycerides, obesity, high blood glucose and high insulin levels are all improved by a low carbohydrate diet. By contrast, the evidence shows that they are not improved, and can even be worsened by low fat/high carbohydrate diets.

Previous research has never explicitly connected low carbohydrate intake and improvement of metabolic syndrome. The general recommendation to patients has been to focus on reducing fat intake. Volek et al. argue that the cause of metabolic syndrome is linked to insulin imbalance. Carbohydrates are the main stimulus for insulin, and reducing carbohydrate can be effective at restoring insulin responses. So reducing carbohydrate intake, not fat intake, should be the main aspect of treatment for metabolic syndrome, the authors argue. This is supported by data from previous research, which shows that carbohydrate reduction is more effective than fat reduction at improving all the components of metabolic syndrome.

Family meals cut teenage fatness

Wed, 02 Nov 2005 13:07:00 PST

( from http://www.rxpgnews.com ) They might prefer to be in front of the TV or Playstation, but Brisbane teenagers are likely to be healthier if they eat meals with mum and dad.

University of Queensland researchers working on the world's longest health study found teens who ate regularly with their family were less likely to be overweight.

Lead researcher, Dr Abdullah Al Mamun from UQ's School of Population Health said regular family meals could reduce snacking and make for healthier food and social habits.

"Eating together will enable the parent to have better knowledge of the child's food choices and amount that they tend to eat," Dr Mamun said of the study, which appears in the latest edition of American journal, Obesity Research.

The study found having a healthy maternal attitude to family eating and diet was more important than the frequency of shared meals.

Even though most mothers said they had a family meal at least once a day, only 43 percent of them said eating together was very or quite important.

The findings have been drawn from the world's longest running health study -- the Mater-University of Queensland Study of Pregnancy, which has followed the progress of Brisbane mothers and their families since 1981.

The survey of 3795 mothers and their teenagers was collected in Brisbane when the teenagers were at age 14, in 1995.

It showed about half the families ate red meat most days and one-fourth had fast food most days or two to three times per week.

Even though more than half of the families had children who played sports four to seven days a week about 40 percent still found enough time to watch five or more hours of TV a day.

Dr Mamun's paper was co-written, with Mater and University of Bristol researchers and fellow UQ researcher and Mater Study founder, Professor Jake Najman.

The Mater Study was started in 1981 by Professor Najman as a health and social study of 7223 pregnant women.

Researchers have followed the children's growth over the decades and study was widened to include prenatal, postnatal, childhood and adolescent periods of the child with those babies now in their early 20s.

Genetics affect the severity of metabolic syndrome

Tue, 25 Oct 2005 22:01:00 PST

( from http://www.rxpgnews.com ) Hereditary factors appear to make obese individuals more susceptible to metabolic syndrome, a disorder associated with excess fat around the abdomen that increases the chances of heart disease, stroke and diabetes.

"Our goal is to gain further understanding of the genetic events that contribute to the metabolic syndrome in obese individuals," said co-researcher Dr. Luigi Bouchard, Université Laval. "The knowledge of genes involved in that syndrome may have considerable public health implications."

Dr. Bouchard's research findings will be presented today at the Canadian Cardiovascular Congress, hosted by the Heart and Stroke Foundation of Canada and the Canadian Cardiovascular Society.

More specifically, metabolic syndrome is defined as a cluster of health conditions including: high blood pressure, high levels of blood fats, insulin resistance, abdominal obesity, and low levels of good cholesterol.

Increased death rate associated with obesity can be explained by the presence of several of these health conditions that define metabolic syndrome. However, a significant proportion of obese individuals can escape many of the health conditions defining this syndrome and remain healthy, whereas other obese individuals show little to many of the metabolic complications associated with metabolic syndrome.

The research team, funded by the Canadian Institutes of Health Research (CIHR) through the strategic initiative Obesity and Healthy Body Weight of the Institute of Nutrition, Metabolism and Diabetes, took a novel approach to the study of the severity of the metabolic syndrome in obese individuals. The study compared the gene expression profiles of the fat cells known as 'visceral adipose tissues' found within the abdominal cavity of obese men, with and without the metabolic syndrome.

"Obesity places a substantial burden on the health of Canadians," said Dr. Diane Finegood, Scientific Director, CIHR's Institute of Nutrition, Metabolism and Diabetes. "Understanding the biologic basis for obesity as a risk factor for co-morbidities such as cardiovascular disease and diabetes may lead to important new therapeutic approaches to preventing these devastating diseases."

"The work of Dr. Bouchard and his team could one day help us identify which obese individuals are most at risk of developing serious health complications", said Dr. Jacques Genest, a Heart and Stroke Foundation researcher and spokesperson.

The study found differences in the gene expression profiles between the study groups. Thereafter, a converging genomic approach was used to prioritize and increase our confidence in the proposed genetic targets that will be further studied. This approach compares differentially expressed genes to chromosomal regions that have been found to harbor metabolic syndrome-genes using a genome scan approach. In summary, this study shows that converging genomics is a powerful method to identify target genes for the metabolic syndrome.

"This kind of research is a perfect example of the multidisciplinary research environment encouraged at CIHR," said Dr. Bruce McManus, Scientific Director, CIHR's Institute of Circulatory and Respiratory Health.

Dr. Bouchard will be presented at the Congress with a Heart and Stroke Foundation/sanofi-aventis Fellowship Award for his work.

The Canadian Institutes of Health Research (CIHR) is the Government of Canada's agency for health research. CIHR's mission is to create new scientific knowledge and to catalyze its translation into improved health, more effective health services and products, and a strengthened Canadian health care system. Composed of 13 Institutes, CIHR provides leadership and support to close to 10,000 health researchers and trainees across Canada.

Systematic review of size and growth in infancy and later obesity

Fri, 14 Oct 2005 21:43:00 PST

( from http://www.rxpgnews.com ) Large infants, and those who grow rapidly during the first two years of life, are at increased risk of obesity in childhood and adulthood, a study published online by the BMJ today (14 October 2005) has found.

There is an urgent need to tackle rising levels of obesity in the population. However it is not clear how early in life prevention could begin. This study examines the relation between infant size and growth and later obesity.

Researchers analysed 24 studies which assessed the relation between infant size and growth and the development of obesity at any later age. They found that the heaviest infants, those with the highest body mass index, and those who gained weight rapidly during the first and second year of life, were more likely to be obese in childhood, adolescence, and early adulthood than other infants.

The authors believe that factors during or before infancy that are related to infant growth probably influence the risk of later obesity.

They suggest that future studies need to investigate what determines these patterns of growth, and to explore whether interventions to alter infant growth could be associated with other benefits or harms.

It will also be important to assess whether factors influencing infant growth are amenable to change, to establish which strategies might alter infant growth, and to find out whether these are acceptable to parents, they conclude.

Is School-Based Enchanced Physical Activity Relevant?

Thu, 06 Oct 2005 21:13:00 PST

( from http://www.rxpgnews.com ) Overweight children who took part in lifestyle-focused, fitness-oriented gym classes showed significant improvement in body composition, fitness, and insulin levels, according to a study in the October issue of the Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

Obesity and poor physical fitness constitute a health problem affecting an increasing number of children. Childhood obesity and poor physical fitness are associated with insulin resistance, type 2 diabetes mellitus, blood lipid abnormalities, and high blood pressure in later life, according to background information in the article. The causes of childhood obesity include a pervasive "toxic" environment that facilitates increased caloric intake and reduced physical activity. In order to alter the children's environment, the authors suggest, an effective strategy for prevention and treatment of childhood obesity must be pervasive and collaborative. The school setting is an attractive starting point for a collaborative effort.

Aaron L. Carrel, M.D., and colleagues at the University of Wisconsin, Madison, conducted a randomized, controlled study to determine whether a school-based fitness program can improve body composition, cardiovascular fitness level, and insulin sensitivity in overweight children. Fifty overweight middle school children were randomized to lifestyle-focused, fitness-oriented gym classes (the treatment group) or standard gym classes (the control group) for nine months. The children were evaluated for fasting insulin and glucose levels, body composition, and maximum oxygen consumption treadmill testing before the school year, and at the end of the school year. There were no differences in age, body mass index, or sex distribution between the groups at baseline.

Fitness-oriented gym classes were designed to make fitness and good nutrition fun and achievable and to maximize the amount of movement during the class period. Class size was limited to 14 students to allow for increased instructor attention, increased opportunity for motivation, and less time standing in line.

"Children enrolled in fitness-oriented gym classes showed greater loss of body fat, increase in cardiovascular fitness, and improvement in fasting insulin levels than control subjects," the authors report.

The authors say the study results suggest that school curricula may be an effective vehicle for increasing physical activity and improving cardiovascular health for children, and they believe further study is warranted. "In this study, even a small change in the amount of physical activity showed beneficial effects on body composition, fitness, and insulin levels in children. Similar benefits have been shown by lifestyle improvements in adults with known glucose intolerance," they write.

The authors emphasize that it is important to develop and evaluate interventions designed to start in childhood, because childhood obesity is predictive of adult obesity. They suggest partnering with school districts should be part of a public health approach to improving the health of overweight children.

"These findings should help to encourage the development of physical education programs that are effective in providing children with substantial amounts of physical activity," they conclude. "Clearly, however, an effective public health approach must promote increased physical activity inside and outside of school, as physical activity recommendations cannot be met through physical education alone."

In an editorial accompanying the article, Oded Bar-Or, M.D., of the Children's Exercise and Nutrition Centre, Hamilton, Ontario, writes that enhanced physical activity is a major pillar in the treatment of juvenile obesity. "To the practicing physician, who is not conversant with exercise sciences, a simple exercise prescription would be an increment of 30 minutes daily, above and beyond the activity already preformed by the patient. To free time for this added activity, the prescription should also include a 30-minute reduction in 'screen time' (computer, video, and, in particular, television). The detailed content of the added activity-preferably outdoors-is not important, as long as the child moves from one place to another and, especially, finds it FUN."

O-GlcNAc sugar helps control cell division

Wed, 28 Sep 2005 13:27:00 PST

( from http://www.rxpgnews.com ) Johns Hopkins scientists have discovered that a deceptively simple sugar is in fact a critical regulator of cells' natural life cycle.

The discovery reveals that, when disturbed, this process could contribute to cancer or other diseases by failing to properly control the steps and timing of cell division, the researchers say. The findings are described in the Sept. 23 issue of the Journal of Biological Chemistry, available online now.

The sugar, known as O-GlcNAc (pronounced oh-GLUCK-nack), is used inside cells to modify proteins, turning the proteins off or on, helping or preventing their interactions with other proteins, keeping them from destruction or allowing their destruction. The comings and goings of the sugar on proteins seem to be important controllers of cell division, say the researchers.

"The dogma for decades has been that the cycle of cell division is controlled by the appearance and disappearance of certain proteins called cyclins, but experiments have shown that you can knock out any of these and still get perfectly normal cell division," says the study's first author, Chad Slawson, Ph.D., a postdoctoral fellow in biological chemistry in Johns Hopkins' Institute for Basic Biomedical Sciences. "In contrast, our experiments show that by increasing or decreasing the amount of sugar attached to proteins, the cell cycle is disrupted and isn't salvageable unless O-GlcNAc levels are fixed."

In experiments with human cells and mouse cells, Slawson and his colleagues showed that preventing a cell from removing the sugar from proteins causes the cell to copy its genetic material and make new nuclei, but to fail to divide in two. The end result is cells with more than one nucleus -- a situation fairly common in cancer cells.

"Cells with more than one nucleus can survive, but they are dysregulated -- things just don't go right," says Slawson. "The longer they survive, the worse it gets."

On the other hand, cells that had higher than normal amounts of the enzyme that removes the sugar from proteins ended up with nuclei that didn't look right under a powerful microscope. Instead of being disseminated fairly uniformly through the entire nucleus, the genetic material of these cells was bunched up, giving the contents of the nucleus a "wrinkly" appearance.

Exactly what is going wrong is still unclear, adds Gerald Hart, Ph.D., professor and director of biological chemistry. He's been studying O-GlcNAc since his lab discovered it attached to proteins inside cells 20 years ago. They now know which enzymes put the sugar onto proteins and which enzymes take it off -- and knocking out or blocking these enzymes allowed the researchers to control whether proteins were sugar-laden or sugar-free.

"Normally, the enzyme that adds the sugar to proteins is enriched at the hub of activity during cell division," notes Slawson. "When we knock it out or block it with a chemical, the cell cycle lengthens and cell division doesn't happen properly. Clearly the enzyme is there for a reason."

But understanding what the sugar itself is doing and how its presence on or absence from proteins affects the cell depends solely on what protein it's being attached to or removed from.

"Whether it's turning something on or off depends on the protein to which the sugar is attached," says Hart. "It's harder than having discovered an enzyme that does just one thing. To figure out the sugar's effect, we have to look at what it's modifying, and the extent and the location of the modification."

The sugar seems to modify as many proteins as the ubiquitous phosphate groups widely recognized as protein controllers, and it frequently seems to compete with phosphate groups for the same spots on proteins. Hart suggests that a particular balance between O-GlcNAc and phosphates on proteins may help fine-tune their activities.

The researchers' next steps are to examine select proteins modified by O-GlcNAc and found at locations important for various steps in cell division to figure out why an imbalance of O-GlcNAc on the cells' proteins has such a dramatic effect on the process.

Inactivity leads to significant increases in visceral fat

Thu, 15 Sep 2005 18:02:00 PST

( from http://www.rxpgnews.com ) Visceral fat, the form which accumulates around the organs inside the belly, particularly concerns physicians because increased levels have been associated with insulin resistance, cardiovascular disease and other metabolic syndromes. Visceral fat is located deeper in the body than subcutaneous fat, which lies just under the skin.

"In our study, the control group that did not exercise saw a sizable and significant 8.6 percent increase in visceral fat in only six months," said Duke exercise physiologist Cris Slentz, Ph.D., lead author of a study published in the October issue of the Journal of Applied Physiology. "We also found that a modest exercise program equivalent to a brisk 30-minute walk six times a week can prevent accumulation of visceral fat, while even more exercise can actually reverse the amount of visceral fat.

"We believe that these results shine a clear spotlight on the high costs Americans are paying for their continued inactivity," Slentz continued. "I don't believe that people in general have gotten lazier it's more that they are working too hard or are at their desks working on computers with fewer opportunities for exercise. The situation is out of balance."

The modest exercise program cited by Slentz is consistent with the latest recommendations by the Centers for Disease Control and Prevention and the American College of Sports Medicine. However, Slentz believes that the public health message needs to be modified, especially for a country where two out of three adults are overweight or obese.

"Until we are able to prevent the weight many dieters regain following short-term dieting success, we should place a greater national emphasis toward prevention," Slentz said. "It will be a challenge to change the message from 'exercise now to lose weight' to 'exercise now so in five years you won't be 20 pounds heavier.'"

To better understand the effects of differing amounts of exercise, the researchers studied 175 overweight sedentary men and women who were beginning to show signs of lipid problems. They were randomized into one of four groups: no exercise, low dose/moderate intensity (equivalent of 12 miles of walking per week), low dose/vigorous intensity (12 miles of jogging per week) or high dose/vigorous intensity (20 miles of jogging per week).

Since the trial was designed solely to better understand the role of exercise, patients were told not to alter their diet during the course of the trial, which lasted six months for the group that did not exercise or eight-months for the exercise groups. The additional two months for the exercise group came at the beginning of trial, when participants slowly ramped up their exercise to their designated levels.

The exercise was carried out on treadmills, elliptical trainers or cycle ergometers in a supervised setting. The researchers used computed tomography (CT) both before the exercise program began and eight months later to determine the extent and distribution of fat change.

"There were no significant changes in visceral, subcutaneous or total fat in either of the low exercise groups for men or women, which suggest that this amount of exercise is adequate to prevent significant gain in fat around the stomach, and that the amount of exercise is more important than the intensity," Slentz said.

"On the other hand, participants who exercised at a level equivalent to 17 miles of jogging each week saw significant declines in visceral fat, subcutaneous abdominal fat and total abdominal fat," Slentz continued. "While this may seem like a lot of exercise, our previously sedentary and overweight subjects were quite capable of doing this amount."

Specifically, those participants exercising at the highest level saw a 6.9 percent decrease in visceral fat and a 7 percent decrease in subcutaneous fat.

Effective diet with no limits on portion size

Mon, 12 Sep 2005 23:08:00 PST

( from http://www.rxpgnews.com ) The study, involving 59 overweight, postmenopausal women, was conducted by Neal D. Barnard, M.D., president of the Physicians Committee for Responsible Medicine (PCRM), together with colleagues at Georgetown University Hospital and George Washington University. Half of the study participants followed a vegan diet; the other half followed a control diet based on National Cholesterol Education Program guidelines.

"The study participants following the vegan diet enjoyed unlimited servings of fruits, vegetables, whole grains, and other healthful foods that enabled them to lose weight without feeling hungry," says Dr. Barnard, the lead author. "As they began to experience the positive effects, weight loss and improved insulin sensitivity, the women in the intervention group became even more motivated to follow the plant-based eating plan."

Scientific studies show that obesity and overweight are far less prevalent in populations following a plant-based diet. In a recent study of more than 55,000 Swedish women, Tufts University researcher P. Kirstin Newby and her colleagues found that 40 percent of meat-eaters were overweight or obese while only 25 to 29 percent of vegetarians and vegans were. Worldwide, vegetarian populations experience lower rates of heart disease, diabetes, high blood pressure, and other life-threatening diseases. A new study appearing in September's Journal of Urology shows that a low-fat, primarily vegan diet may slow the progression of prostate cancer.

The simplicity of a vegan diet appeals to people who are busy with work and family, and many familiar recipes are easy to adapt. At least four studies published in peer-reviewed journals show that patients give the low-fat vegetarian diet a high rating in terms of acceptability, and that the transition only takes about three weeks or less.

Is suburban life making people overweight?

Sat, 10 Sep 2005 23:21:00 PST

( from http://www.rxpgnews.com ) In a study recently published in the Journal of Regional Science, researchers from Oregon State University found that the relationship between obesity and urban sprawl may be a two-way street.

Economists Andrew Plantinga from OSU's Department of Agricultural and Resource Economics and Stephanie Bernell from OSU's Department of Public Health expanded previous studies that showed that people living in areas of urban sprawl tend to have higher body mass indices. Their analysis suggests that the relationship between obesity and urban sprawl may be due to personal preferences when choosing a home location rather than to direct impacts of the suburban environment on physical activity and weight.

Location, location, location. Research by Plantinga and Bernell suggests that an individual's body weight is a factor determining the desirability of a residential location. They found the relationship between obesity and urban sprawl can be explained by the way people sort themselves by personal preference.

In a follow-up study, Plantinga and Bernell used a national data set to test whether body mass index influences the decisions of adults to locate in counties with a high or low degree of sprawl. To measure body weight, the researchers used data from the U.S. Department of Labor's National Longitudinal Survey of Youth, which has tracked statistics on thousands of individuals since their youth in 1979. The researchers examined many factors, among them ethnicity, gender, age, income, education, marital status and body weight.

"Among people who moved recently, we find that in addition to a high body mass index, being female, younger, and married increases the probability of choosing to reside in a sprawling county," Bernell said.

"In many sprawling areas, distances are too great for people to walk to work or to the store," Plantinga explained. "Transportation infrastructure is often designed for automobiles, with the result that walking and bicycling are impractical and unsafe. The incentives are for people to drive instead of walk. In contrast, in urban neighborhoods like the Pearl District in Portland, Ore., people can walk to work, school, or shopping. In many cases, it's easier to walk to the store than to drive."

Previous studies had suggested that the relationship between obesity and urban sprawl is related to suburban environments that discourage routine physical activity such as walking and biking. However, previous studies did not consider the choices people make in selecting where to live.

"When you select a residential location, you are really choosing a bundle of attributes," Plantinga said. "The house you choose may be near a shopping center or a park, or it may have a three-car garage and a bonus room. The market prices each of these attributes. It follows that individuals, given their income, will choose locations that provide the attributes of greatest value to them. People who value walking will tend to choose walkable neighborhoods. People who do not care for walking will tend not to."

These findings have implications for urban planners and public health officials, according to Plantinga. Many recent planning initiatives include funding for bicycle and pedestrian facilities in order to increase physical activity. However, making communities more exercise-friendly may simply attract people who are predisposed to physical activity.

Potential health risks from 'Ephedra-free' dietary supplements

Sat, 10 Sep 2005 23:08:00 PST

( from http://www.rxpgnews.com ) The research examined the effects on blood pressure and heart rate of two dietary supplements containing bitter orange extract -- a substance that has rapidly replaced ephedra in weight-loss products since it was banned by the FDA in 2004 because of concerns about serious health effects.

The study involved 10 healthy adults given single doses of one of the two supplements or a placebo. The two supplements tested were Advantra Z and Xenadrine EFX. Single doses of both products increased heart rate by an average of 11 to 16 beats per minute over baseline, the scientists found. This would be the equivalent of an 18 percent increase if baseline rate is 80 beats per minute.

In addition, Xenadrine EFX also significantly increased blood pressure by 7 to 12 percent (9-10 mm Hg), the researchers reported. Xenadrine EFX appears to have similar acute cardiovascular stimulant actions as banned ephedra products, according to their report.

"These findings indicate that ephedra-free dietary supplements could have some of the same adverse health effects associated with previously available ephedra products, such as Metabolife 356 and Ripped Fuel," said Christine Haller, MD, UCSF assistant professor of medicine and lead author of the paper.

The scientists call for further research on the safety and effectiveness of bitter orange- containing supplements -- particularly among those most likely to take them: overweight people who may have other health conditions.

Bitter orange extract, or Citrus aurantium, is extracted from the dried fruit peel of bitter orange. Known in Chinese herbal medicine as Zhi shi, it is a traditional remedy for gastrointestinal ailments, the scientists said.

The predominant constituent of bitter orange is synephrine, which in pharmaceutical form is commonly used to treat low blood pressure and nasal congestion.

Advantra Z contains only bitter orange, while one dose of Xenadrine EFX contains several other ingredients, including caffeine equivalent to the amount in 3 cups of coffee, the researchers found. The increased blood pressure from taking Xenadrine EFX is likely not due to caffeine alone, they concluded, but potentially related to the actions or interaction of other constituents in the multi-ingredient supplement.

The scientists call for longer term dosing studies to determine whether the blood pressure effects of Xenadrine EFX persist with repeated use. Until such data are available, they conclude, doctors should caution patients about using ephedra-free weight-loss dietary supplements and should monitor blood pressure in those who choose to use the products.

In particular, people with hypertension, heart disease or other pre-existing conditions that could be aggravated by the supplements should avoid them.

"Consumers should be aware that ephedra-free dietary supplements have not been extensively tested for safety and the health effects are not well known," Haller noted.

Among other physiological measures, heart rate and blood pressure were recorded in the study for an hour before dosing and then at several intervals afterwards.

To rate physical symptoms, moods and emotions, questionnaires were administered one, two and six hours six hours after taking the supplements or placebo.

The caffeine-containing Xenadrine EFX product also increased alertness according to responses on the questionnaire. But neither product appears to have a significant effect on mood, the study found.

Obesity strongly linked to DVT & PE

Sat, 10 Sep 2005 15:08:00 PST

( from http://www.rxpgnews.com ) Since 1927, obesity has been thought to be a risk factor for fatal pulmonary embolism (PE). Because of the high proportion of obesity in the general population, previous studies have not determined whether obesity is an independent risk factor for PE or deep venous thrombosis (DVT). In an extensive study published in the September issue of The American Journal of Medicine, researchers from St. Joseph Mercy Oakland Hospital, Pontiac, Michigan; Wayne State University, Detroit, Michigan; and Oakland University, Rochester, Michigan; analyzed over 20 years of patient records compiled by the National Hospital Discharge Survey (NHDS) to further investigate the potential risk of obesity in venous thromboembolism. The investigators concluded that obesity is a risk factor for venous thromboembolic disease in men as well as women, particularly those under age 40.

The NHDS is comprehensive in its scope including data on patients of all races and ages obtained annually from 181,000 to 307,000 sampled patient abstracts from 400 to 494 non-Federal short-stay hospitals in 50 states and the District of Columbia. There were more than 12,000,000 obese patients and almost 700,000,000 non-obese patients in the sampled data.

The relative risk of DVT, comparing obese patients with non-obese patients, was 2.50. The relative risk of PE was 2.21. Obese females had a greater relative risk for DVT than obese males, 2.75 versus 2.02. Obesity had the greatest impact on patients aged less than 40 years, in whom the relative risk for PE in obese patients was 5.19 and the relative risk for DVT was 5.20. In females aged less than 40 years, the relative risk for DVT comparing obese with non-obese patients was 6.10. In males less than 40 years of age, the relative risk for DVT was 3.71.

Paul D. Stein, MD, writes "Now that we know with certainty that obesity is a risk factor for PE, particularly in men and women under age 40, the presence of obesity may alert physicians to a possibility of the diagnosis. The diagnosis of PE is frequently missed even though PE is the third most common acute cardiovascular disease after myocardial infarction and stroke."

Potential metabolic effects of telmisartan in preliminary studies

Thu, 08 Sep 2005 01:34:00 PST

( from http://www.rxpgnews.com ) Preclinical studies show that the angiotensin II receptor blocker (ARB), Micardis® (telmisartan), has a beneficial effect on metabolic parameters including plasma glucose, insulin resistance and lipid abnormalities, in addition to its proven effect on high blood pressure, due to its partial activation of PPAR-gamma (peroxisome proliferator-activated receptor-gamma).1-4 PPAR-gamma is a hormone receptor known to have an important role in regulating carbohydrate and lipid metabolism, by increasing insulin sensitivity.1-5 High blood pressure, lipid abnormalities, insulin resistance and obesity are key components of metabolic syndrome, a common precursor of cardiovascular disease and type 2 diabetes.6 The implications of these findings were discussed today by leading experts at a meeting in Stockholm, Sweden, coinciding with the European Society of Cardiology Annual Meeting.

These preclinical findings are very exciting and suggest Micardis® may have a uniquely beneficial metabolic effect. We have effective treatments for some of the individual components of metabolic syndrome, such as high blood pressure, but we need to tackle the different risk factors concurrently, Professor Ted Kurtz, University of California, USA, commented. These are very early days but given the major impact of the metabolic syndrome on cardiovascular morbidity and mortality, any treatment that could tackle more than one of the components of metabolic syndrome would provide a huge advantage to patients and physicians in the fight against cardiovascular disease.

The Micardis® molecule is structurally similar to the PPAR-gamma activator, pioglitazone,3 which has been approved for the treatment of type 2 diabetes.7 Micardis® partially activates PPAR-gamma resulting in metabolic effects that differentiate it from other ARBs, according to preclinical data.1-4 These data demonstrate that Micardis® has a beneficial effect on insulin resistance and blood lipids, independent of its effect on the renin-angiotensin-aldosterone system (RAAS).1-4

Studies by Schupp et al and Kurtz et al showed Micardis® is a more potent PPAR-gamma activator compared to other commercially available ARBs.1-2 Furthermore, an in vitro and in vivo study reported by Benson et al showed Micardis® significantly reduced serum glucose levels (p<0<0<0

How glycerol may hold water 'in reserve' in body for use later

Sun, 04 Sep 2005 09:02:00 PST

( from http://www.rxpgnews.com ) For over 20 years, the U.S. Army Research Institute of Environmental Medicine has studied the effect of temperature and the environment on physical performance. According to Michael Sawka, chief of USARIEM's Thermal and Mountain Medicine Division, "we're filling in the data gaps regarding the interaction of temperature and hydration on physical performance so we can set guidelines to optimize results relevant not just to soldiers or navy divers, but to athletes, firefighters and hunters anyone who's in extreme environments without access to food or water for long periods."

Several recent USARIEM studies in the Journal of Applied Physiology describe experiments in both warm and cold temperatures. One report showed that dehydration reduces physical performance, in this case cycling, 8% in temperate/cool air (68 degrees Fahrenheit), but only 3% in a cold 36 degrees F. Furthermore it found that cold weather itself had an insignificant impact on physical performance, irrespective of hydration level.

A second USARIEM-generated study found that ingesting glycerol, a sweetish syrup, was an effective hyperhydration agent, causing "nearly twice as much fluid" to be retained after four hours of cold-air exposure (CAE) compared with water ingestion alone. "This study also demonstrates that hyperhydration doesn't modify cardiovascular or thermoregulatory responses during resting CAE," the reported added.

How glycerol may hold water 'in reserve' in body for use later

The implications of the second study are particularly interesting for prolonged outdoor exposure when rehydration is not possible. "Because glycerol is freely distributed in body water, hyperhydration with GI (glycerol ingestion) may better preserve the extravascular fluid volume, accounting for the improved TBW (total body water), compared with water alone. This extravascular 'reserve' could later be called on during exercise or heat stress, when hydration becomes important to performance and thermoregulation," the paper noted.

Catherine O'Brien, lead author of the glycerol study, said "there's a window of two to six hours where GI could be beneficial. That's a narrow niche where it might be useful for instance for soldiers on short-range patrol with inadequate access to rehydration." The paper noted that the experiments supported earlier findings "suggesting that glycerol induced hyperhydration through renal reabsorption of water and glycerol. Finally, this study provides insight into the hormonal mechanisms of cold-induced diuresis and fluid shifts due to hyperhydration."

Next steps

"Whether the degree of hyperhydration" in the current study "is sufficient to improve physical performance in the cold or thermoregulation during subsequent body warming due to exercise or heat exposure remains to be demonstrated," the paper noted.

In addition, O'Brien said: "We learned previously that hydration doesn't seem to affect susceptibility to frostbite. But soldiers and outdoorsmen are more affected by their hands and fingers getting stiff. We're going to look at how physical performance such as manual dexterity can better be maintained in the cold."

Some dehydration shows no performance effect in cold, but does as temperature rises

It's well recognized that athletes perform progressively better as the temperature falls from hot to cool. It is also known that dehydration worsens performance in the heat, but its effect in milder environments is not well understood. A USARIEM team led by Samuel N. Cheuvront found that dehydration by 3% of body weight had little adverse impact on cycling performance in the cold (36F), but markedly reduced performance in temperate air (68F).

"We induced a 3% body weight loss because that's about how much water the average marathon runner loses," Cheuvront noted. The team found that while this much dehydration produced only a minor negative affect at 36F, at 68F it made a significant 8% cut in performance. "We measured performance as work performed (in kilojoules), but the real indicator is time: 8% over the course of a marathon is the difference between finishing in 2 hours 30 minutes or 2 hours 42 minutes and that's a big difference!" Cheuvront said.

He added a quick note of realism, though: "Remember that although we're testing healthy and fit Army recruits, the average competitive runner's performance might not drop as drastically." The other important finding in the experiment was that with hydration kept steady, cold in and of itself did not negatively impact performance.

Some elegant measures of "importance" and exertion

Interestingly, the researchers found that during exercise the subjects "thought" they were working at exactly the same rate of exertion, even though there was a major difference between their actual performances.

Another measure they used is called the "zone of indifference," which can indicate not just whether a finding is or is not "statistically significant, but if it's biologically important or meaningful," Cheuvront said. "In this case the results were both statistically significant and meaningful," he added. The "spirit of this approach, most closely related to equivalence testing in the clinical sciences, has recently been championed as a performance interpretation tool for the exercise sciences by Dr. William G. Hopkins," the paper noted.

Next steps: "The preservation of endurance performance in cold air when hypohydrated may be explained by differences in cardiovascular function and oxygen uptake dynamics," the paper said. "Although the present experiment was not designed to assess the mechanism behind performance changes, the explanation is reasonable based on the work of others," it added.

A Genetic Link to Obesity: The Numbers Don't Add Up for GAD2

Wed, 31 Aug 2005 02:09:00 PST

( from http://www.rxpgnews.com ) Obesity is a leading cause of preventable death and is often linked to type II diabetes and heart disease. Being a complex trait, obesity is likely caused by the interplay of multiple environmental factors and many genes. Common genetic differences between individuals within a region of Chromosome 10 have previously been associated with obesity. This region contains several genes with the potential to be directly involved in the disease. One of these genes, GAD2, has been the subject of many studies. A new study by Michael Swarbrick, Björn Waldenmaier, Christian Vaisse, and their colleagues takes a new look at GAD2 and provides strong evidence that the gene might not be as relevant to obesity as previously thought.

GAD2 encodes a protein (called GAD-65) involved in the production of GABA, a neurotransmitter involved in a variety of brain functions, including appetite stimulation and energy consumption. Studies in mice have shown that increased levels of GABA result in hunger and overeating. In healthy mice, the levels of GAD2, and hence, GABA, are controlled, making sure that the balance between weight gain and loss is maintained. A 2003 study of a French population found that three genetic mutations in and around the GAD2 gene occurred at a high level in individuals with obesity. The 2003 study, conducted by different researchers, was also published in PLoS Biology. When Swarbrick et al. surveyed German, Caucasian-American, and Canadian populations for this genetic correlation, however, they found no statistically significant link between obesity and any of the mutations.

There are many possible reasons why different studies may show different results: ethnic differences between populations, as well as behavioral and dietary differences, could account for varying results when it comes to studying a trait as complex as obesity. Also, studies that seek to show an association between genetic differences and complex diseases rely heavily on the statistical power of their tests, which depends on the number of subjects involved. Swarbrick et al. have not only studied 2,359 German, 729 US, and 1,137 Canadian subjects, but also conducted a meta-analysisa statistical analysis of a collection of individual studiesof their data and the previously published data from 1,221 French subjects. Meta-analyses help identify patterns from multiple individual studies that may not be visible in any one study alone, and also help rule out chance differences that may be apparent in one single study. In this case, the meta-analysis showed that when the results from French subjects are put together with the results from other ethnic populations, there is no evidence for a link between changes in GAD2 and obesity.

Although GAD2's role in controlling appetite made it an exciting candidate for a link to obesity-related conditions, Swarbrick et al. show that the numbers simply don't add up. The search for serious obesity gene contenders in this region of Chromosome 10 is all set to continueand attention can now turn to several other potential gene candidates located nearby.

That steaming cup of java is also the top antioxidant source

Mon, 29 Aug 2005 22:52:00 PST

( from http://www.rxpgnews.com ) Coffee provides more than just a morning jolt; that steaming cup of java is also the number one source of antioxidants in the U.S. diet, according to a new study by researchers at the University of Scranton (Pa.). Their study was described today at the 230th national meeting of the American Chemical Society, the world's largest scientific society.

"Americans get more of their antioxidants from coffee than any other dietary source. Nothing else comes close," says study leader Joe Vinson, Ph.D., a chemistry professor at the university. Although fruits and vegetables are generally promoted as good sources of antioxidants, the new finding is surprising because it represents the first time that coffee has been shown to be the primary source from which most Americans get their antioxidants, Vinson says. Both caffeinated and decaf versions appear to provide similar antioxidant levels, he adds.

He cautions that high antioxidant levels in foods and beverages don't necessarily translate into levels found in the body. The potential health benefits of these antioxidants ultimately depends on how they are absorbed and utilized in the body, a process that is still poorly understood, says Vinson, whose study was primarily funded by the American Cocoa Research Institute.

The news follows a growing number of reports touting the potential health benefits of drinking coffee. It also comes at an appropriate time: Coffee consumption is on the rise in the United States and over half of Americans drink it everyday, according to the National Coffee Association.

Antioxidants in general have been linked to a number of potential health benefits, including protection against heart disease and cancer. For the current study, Vinson and his associates analyzed the antioxidant content of more than 100 different food items, including vegetables, fruits, nuts, spices, oils and common beverages. The data was compared to an existing U.S. Department of Agriculture database on the contribution of each type of food item to the average estimated U.S. per capita consumption.

Coffee came out on top, on the combined basis of both antioxidants per serving size and frequency of consumption, Vinson says. Java easily outranked such popular antioxidant sources as tea, milk, chocolate and cranberries, he says. Of all the foods and beverages studied, dates actually have the most antioxidants of all based solely on serving size, according to Vinson. But since dates are not consumed at anywhere near the level of coffee, the blue ribbon goes to our favorite morning pick-me-up as the number one source of antioxidants, he says.

Besides keeping you alert and awake, coffee has been linked to an increasing number of potential health benefits, including protection against liver and colon cancer, type 2 diabetes, and Parkinson's disease, according to some recently published studies. But there's also a downside: Java can make you jittery and cause stomach pains, while some studies have tied it to elevated blood pressure and heart rates. More research is needed, particularly human studies, to firmly establish its health benefits, Vinson says.

While the findings would seem to encourage people to go out and drink more coffee, Vinson emphasizes moderation. "One to two cups a day appear to be beneficial," he says. If you don't like coffee, consider drinking black tea, which is the second most consumed antioxidant source in the U.S. diet, Vinson says. Bananas, dry beans and corn placed third, fourth and fifth, respectively.

But don't forget about fresh fruits and veggies, the researcher cautions. "Unfortunately, consumers are still not eating enough fruits and vegetables, which are better for you from an overall nutritional point of view due to their higher content of vitamins, minerals and fiber," Vinson says. Dates, cranberries and red grapes are among the top fruits for antioxidants on the basis of concentration (antioxidants per serving size), he says.

Graffiti linked to obesity in city dwellers

Fri, 19 Aug 2005 13:57:00 PST

( from http://www.rxpgnews.com ) City dwellers living in areas with little greenery and high levels of graffiti and litter are more likely to be obese than those living in pleasant areas with lots of greenery, say researchers in a study published on bmj.com today.

Obesity levels are high and increasing worldwide, and studies have suggested that place of residence may be associated with levels of obesity and physical activity. Evidence also suggests that levels of incivilities, such as litter and graffiti, are linked to poorer health.

Based on this work, the team set out to test the theory that areas which are pleasant with lots of greenery and few incivilities might encourage people to take exercise and thereby influence levels of obesity.

They analysed data from a large housing and health survey conducted in eight European cities in 2002-3. Questionnaires captured information on height and weight, which was then used to calculate body mass index, and level of physical activity.

Surveyors then assessed the immediate residential environment, including the amount of graffiti, litter, and dog mess, as well as the level of vegetation and greenery visible on the dwelling and streets immediately surrounding it. Factors such as age, sex, and social status, were also taken into account.

For respondents whose residential environment contained high levels of greenery, the likelihood of being more physically active was over three times as high, and the likelihood of being overweight and obese was about 40% less.

In contrast, for respondents whose residential environment contained high levels of incivilities, the likelihood of being more physically active was about 50% less, and the likelihood of being overweight or obese was about 50% higher.

Despite some limitations, these findings suggest that efforts to promote physical activity and reduce weight should take into account environmental facilitators and barriers as well as individual factors, conclude the authors.

Possible drug targets for treating metabolic syndrome outlined

Thu, 11 Aug 2005 17:29:00 PST

( from http://www.rxpgnews.com ) Ongoing studies by researchers at UT Southwestern Medical Center and other institutions have uncovered the biochemical basis of many of the factors contributing to what is known as the metabolic syndrome, suggesting potential new drug targets for treating the condition.

The metabolic syndrome, which affects more than 47 million Americans, is a constellation of disorders of the body's metabolism - such as abdominal obesity, hypertension and insulin resistance - that increase one's risk of heart disease, dangerous plaque buildup in artery walls and non-insulin-dependent diabetes.

In a review article in the Aug. 11 issue of The New England Journal of Medicine, UT Southwestern's Dr. David Mangelsdorf, professor of pharmacology and biochemistry, and Dr. Andrew Shulman, a Medical Scientist Training Program fellow, examine how one category of proteins found in the cell's nucleus, called retinoid X receptor heterodimers, are promising novel drug targets for treating the metabolic syndrome.

"Our research has taught us that that these receptors are potentially legitimate therapeutic targets that show great promise," Dr. Mangelsdorf said. "But we also have learned that, as with any drug development, it is going to be a challenge to come up with the right drug or drugs to do the job."

The metabolic syndrome, sometimes referred to as syndrome X, is characterized by multiple risk factors, with the underlying causes being obesity, physical inactivity and genetic factors. The characteristic disorders present in the metabolic syndrome include: excessive fat tissue in and around the abdomen; high blood pressure; insulin resistance or glucose intolerance; blood fat disorders, mainly high triglycerides and low high-density lipoproteins, or "good" cholesterol; and abnormalities in blood clotting.

Any one of these disorders by itself is a risk for certain diseases, but in combination they can dramatically boost one's chances for developing life-threatening illnesses, said Dr. Mangelsdorf, a Howard Hughes Medical Institute investigator.

"One person may have a more severe case of type 2 diabetes, for example, or another person may not have hypertension, yet they may all have the syndrome," he said. "There's not one factor that overrides everything else.

Lipid, or fat, metabolism is an important component, however, and in fact, lipid metabolism may drive the syndrome. The question is, why?"

The answer may lie in research conducted by Dr. Mangelsdorf and others that identified the protein retinoid X receptor, or RXR, which play`s a key role in lipid metabolism. This protein can bind to several other so-called nuclear receptors to form distinct molecular complexes called heterodimers. Each complex then can go on to control certain genes involved in regulating lipid and cholesterol metabolism.

"When RXR is paired with a nuclear receptor called PPAR-gamma, for example, it activates one set of genes," Dr. Mangelsdorf said. "When RXR is paired with another receptor called LXR, it acts on a different set of genes. All of the genes, however, are involved with lipid metabolism."

Drugs that target RXR and its binding partners are already in clinical use or trials for the treatment of cancer, dermatological disorders, endocrine disorders and some aspects of the metabolic syndrome. In their review article, Drs. Mangelsdorf and Shulman outline promising research findings on how drugs that target RXR complexes may be used in the management of the metabolic syndrome.

One of the challenges to developing therapies targeting these receptors is that activating or blocking a given receptor can have both positive and negative effects on the body. The trick, Dr. Mangelsdorf said, is to develop drugs that selectively act on a particular receptor to activate only the good effects while dialing out the bad effects.

For example, activating the LXR receptor, which binds with RXR to modulate cholesterol levels, also has the effect of increasing fat synthesis, which is undesirable, Dr. Mangelsdorf said.

Some drugs that selectively modulate nuclear receptors have already proved successful as cancer drugs. For instance, tamoxifen citrate acts on estrogen receptors to selectively block the activity of estrogen in breast tissue while acting like estrogen in other tissues, where it slows bone loss and lowers blood cholesterol.

Little evidence for dietary antioxidant supplements

Thu, 11 Aug 2005 03:12:00 PST

( from http://www.rxpgnews.com ) A leading researcher at the University of New South Wales (UNSW) points out that there is little convincing evidence that dietary antioxidant supplements such as vitamin E prevent heart disease, despite claims to the contrary.

Instead there has been a surprise finding, which relates to a synthetic antioxidant, the drug Probucol, which is no longer prescribed in Australia.

"There has been a lot of hype which suggested that antioxidant vitamin supplements had a beneficial outcome for cardiovascular disease. There is no good scientific support for the notion that people who suffer from atherosclerosis, or who are at elevated risk of heart disease, gain benefit by supplements of vitamin E," said Professor Roland Stocker, from the Centre for Vascular Research at UNSW, who will present his research at the ISTH Congress in Sydney today.

Stocker reported, "Our research is now leading towards the development of a new drug, based on Probucol. Probucol was previously used to reduce so-called "bad" cholesterol for those with heart disease, but it also had side effects, such as reducing "good" cholesterol and possibly inducing an irregular heartbeat.

This new compound, which has a similar structure to probucol, is very effective in protecting against atherosclerosis (the principal cause of coronary heart disease) in animal models but doesn't have the same side effects"

He went onto say, "We have shown that this novel probucol-analog induces a pathway in the vessel wall which is both anti-oxidative and anti-inflammatory. The early signs are that it provides strong protection for blood vessel walls. We are now progressing these studies further with a pharmaceutical company."

"This compound potentially represents a new approach for treating people with or at risk of heart disease at the source of the problem in the vessel wall. Vitamin E is not depleted or deficient in people with heart disease. It is in my view, a naïve idea that vitamin E supplements would work," said Stocker.

Taking a break from fractures: A closer look at vitamin D

Wed, 10 Aug 2005 12:51:00 PST

( from http://www.rxpgnews.com ) With an aging population, and with people living longer, experts say bone fractures will become a bigger and more costly problem unless more is done to prevent them. Osteoporosis (reduced bone mineral density) is most common in older adults, particularly women. It is a major risk factor for bone fractures, which can cause significant suffering while carrying high economic costs. While vitamin D has been shown to reduce the risk of fracture in the elderly, a study recently published in the Journal of the American Medical Association (JAMA) raises the question of how much vitamin D is enough.
The Recommended Dietary Allowance (RDA) of vitamin D for older adults is between 400 and 600 International Units (IU) per day. In their review of the existing literature, a team of scientists including senior author Bess Dawson-Hughes, MD, director of the Bone Metabolism Laboratory at the Jean Mayer USDA Human Nutrition and Research Center on Aging at Tufts University, found that this dose was not effective in reducing nonvertebral fracture rates among study participants. The researchers concluded, though, that higher daily doses, in the range of 700 to 800 IU, may reduce the risk of fracture by approximately 25 percent.

Dawson-Hughes and her colleagues analyzed the results of seven experimental trials that all compared fracture rates among subjects 60 years of age and older given vitamin D supplements (with or without calcium supplements) to those among similar subjects given only calcium or placebo. Each study lasted between one and five years, and looked specifically at hip fractures or other fractures that did not involve the spine. The researchers found that only subjects receiving higher doses of vitamin D supplementation had significantly fewer fractures than did subjects in the comparison groups.

"In the future, we may need to reconsider the current recommended daily values of vitamin D for older adults," says Dawson-Hughes. She adds, "We also need to look more closely at the possible role that calcium supplementation may have in mediating the effects of vitamin D. Fractures in the elderly can lead to severe health consequences, including death. One promising prevention strategy may be dietary supplementation with both calcium and vitamin D."

Another meta-analysis on vitamin D published in JAMA last year found that older adults can reduce their risk related to falls by more than 20 percent by ensuring they get enough vitamin D. Dawson-Hughes, an author on that paper, noted that "vitamin D may also improve muscle strength, thereby reducing fracture risk through fall prevention."

Obesity interventions in children have limited effect

Wed, 20 Jul 2005 15:07:00 PST

( from http://www.rxpgnews.com ) Many diet and exercise interventions aimed at preventing childhood obesity promote healthy diets and increased physical activity, but do not appear to have radical impacts on reducing overweight and obesity gain.

The epidemic of child obesity demands serious action, and around the world many people have looked at ways of helping children eat less and exercise more. In preparing this review, the Cochrane Review Authors identified 22 studies that between them tested a variety of different approaches involving changes to diet, exercise, or diet and exercise. By pooling data, the review drew on findings from about 10,000 participants who were under 18 years old and came from Asia, South America, Europe and North America.

While the authors were unable to identify one particular program that could prevent obesity in children lead-author, Carolyn Summerbell, a Professor of Human Nutrition who works at the University of Teesside, England, believes that any intervention that leads to a better lifestyle will reduce obesity if it is kept up for long enough.

Summerbell believes that the most effective programmes are the ones that put fun into fitness and good food. This means that features like dance and martial arts should be included alongside traditional sports and physical exercise in the school curriculum.

Despite the importance of childhood obesity, the review was only able to find a limited number of studies to draw findings from and some of these were pilot projects that showed great promise but were not designed to be able to measure changes in body weight.

"It is becoming increasingly clear that decision-makers need much more information on which to base policy and program decisions," says Professor Elizabeth Waters, who is a professor of Public Health based at Deakin University, Melbourne, Australia.

The authors note that there are many different programmes underway at the moment, and look forward to seeing the outcomes. "We believe that programmes aimed at creating environments that enable and support long-term behaviour change are likely to make more of a positive impact than the interventions that people have studied so far," Waters adds.

"This review made a central contribution to the WHO Expert Consultation on childhood obesity at Kobe, Japan, in June 2005, and the report of this consultation will be published in June 2006. As one of a number of reviews where a controlled evaluation has been used it makes a valuable contribution to our understanding of childhood obesity. But given the importance of tackling childhood obesity it is clear that there is a need for much more research in the area, and research that is thoroughly designed so that it generates useful data," says Summerbell

Metabolic syndrome increase risk of blocked arteries

Thu, 26 May 2005 18:47:00 PST

( from http://www.rxpgnews.com ) Now, researchers at Cedars-Sinai Medical Center have found that patients with metabolic syndrome and a moderate level of calcium in the coronary arteries had a greater chance of having blockage of those arteries, as detected on a stress imaging test. The findings, reported in the June issue of Diabetes Care, show that analyzing a patient's metabolic profile in relation to their coronary calcium levels will help physicians identify patients who need stress testing so that effective treatment measures can be taken.

"Metabolic syndrome is very similar to diabetes in accelerating heart disease," said Daniel Berman, M.D., the director of Cardiac Imaging at Cedars-Sinai Medical Center and senior author of the study. "Importantly, our findings reveal that patients with the metabolic syndrome who had only moderate amounts of calcium in their coronary arteries had a significantly greater chance of having ischemia too little blood flow to the heart during a stress test."

Coronary calcium indicates the presence of atherosclerosis plaque build-up in the arteries surrounding the heart. The amount of coronary calcium in the arteries, called a calcium score, is measured by using computed tomography (CT) scanning to obtain cross-sectional pictures of the heart and surrounding arteries. Even when patients have no symptoms, their coronary calcium score directly correlates with their long-term risk of cardiac events, such as a heart attack, or sudden death. Calcium scores of zero are the best scores; scores between one and 100 are considered mild and correlate with a low risk for any cardiac event over the ensuing five years. Patients with moderate calcium scores of 100 to 400 are at increased or intermediate risk for cardiac events, and patients with extensive coronary calcium (score over 400) are at even higher risk.

"Although coronary calcium scores provide an excellent measure of plaque build-up in the arteries, the presence of calcium doesn't mean that we will see evidence of ischemia or artery blockage when a patient does a stress test," Berman said. "In most patients, the calcium buildup causes the artery to expand outward, without blocking the vessel, and does not cause ischemia. This occurrence is associated with a low likelihood of a cardiac event over the next few years but a relatively high long-term risk. Regardless, the calcium scan correctly identifies these patients as needing aggressive medical treatment to reduce their risk for a cardiac event, but they don't need to be considered for angioplasty or bypass surgery."

Still, some patients with coronary calcium have arteries that are partially blocked, restricting blood flow to the heart muscle during stress. The most widely used approach to detect blocked coronary arteries is stress imaging, during which patients exercise on a treadmill or, if they can't, are given medication that causes the heart's arteries to dilate. Once the patient reaches "peak" stress, a small amount of radioactive imaging agent is given that concentrates in the heart according to blood flow, emitting signals that are captured by a special type of camera. The cardiac images show the parts of the heart which do not get enough blood flow during stress and is very effective in predicting short-term risk of a cardiac event and determining whether it is necessary to consider angioplasty or surgery at that time.

To test whether the presence of metabolic syndrome might help identify patients at highest risk for coronary artery blockage, the researchers evaluated 1,043 patients without any known heart disease who underwent a coronary calcium scan and stress imaging within a three-month time period. They found that metabolic abnormalities were present in a total of 313 or 30 percent of patients. Among these patients, 140 had diabetes, while 173 had metabolic syndrome without diabetes.

The investigators then compared coronary calcium scores and stress test results of the three groups of patients: those without metabolic syndrome, those with metabolic syndrome, and those with diabetes. They found that 15 percent of metabolic syndrome patients with moderate calcium scores between 100-399 (a level which is generally not considered high enough to require stress testing) had ischemia on stress imaging indicating blocked arteries. Importantly, these patients were also as likely to have these stress test abnormalities as were patients who had extensive calcification but no metabolic abnormalities. Similar findings were observed in patients with diabetes and those with the metabolic syndrome.

When coronary calcium scores were greater than 400, the amount of blockage identified on stress tests among patients with metabolic syndrome was significantly higher compared to those without the disorder, (23.4 percent vs. 13.6 percent). Among patients with calcium scores below 100, only about three percent had artery blockage that was detected by stress testing.

"Our findings suggest that patients' coronary calcium scans need to be interpreted in light of whether or not they have metabolic syndrome or diabetes, in order for us to best determine which patients need to be referred for stress testing. Contrary to previous thinking, our data show that patients with the metabolic syndrome or diabetes deserve earlier stress testing than patients without those metabolic abnormalities," Berman said. "If our findings are confirmed in additional clinical trials, the practice guidelines for stress testing are likely to be changed so that more patients with metabolic syndrome can be stress tested, allowing those with ischemia those who are at highest risk for heart attack to be identified and appropriately treated."

Metabolic syndrome - bad prognosis in MI

Thu, 26 May 2005 03:00:00 PST

( from http://www.rxpgnews.com ) Nearly half of heart attack patients also met criteria for metabolic syndrome, putting them at a higher risk for development of heart failure, according to an article in the May 23 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

Metabolic syndrome is a group of risk factors in an individual that may precede type 2 diabetes mellitus, according to background information in the article. The definition for metabolic syndrome includes thresholds for waist circumference, concentrations of triglycerides, high-density lipoprotein (HDL) cholesterol (the "good cholesterol"), fasting blood glucose levels, and elevated blood pressure. A survey found that metabolic syndrome was prevalent in 25 percent of white Americans and 44 percent of people 50 years and older. The effect of metabolic syndrome after acute myocardial infarction (AMI, heart attack) has not yet been studied.

Marianne Zeller, Ph.D., from the University of Burgundy, Dijon, France, and colleagues examined the prevalence of metabolic syndrome in 633 patients hospitalized with AMI. Patients were enrolled if they were 18 years or older and were admitted to the hospital within 24 hours of the onset of heart attack symptoms. Participants were diagnosed with metabolic syndrome if they had three of five criteria: a waist circumference greater than 102 cm (40 inches) in men and 88 cm (35 inches) in women, high triglyceride levels, low HDL cholesterol levels, high blood glucose level, and high blood pressure.

The researchers found that 46 percent (n = 290) of patients met the criteria for metabolic syndrome. Patients with metabolic syndrome were older, more likely to be women, had a more frequent history of previous MI than patients without metabolic syndrome, and had a higher number of cardiovascular risk factors. The metabolic syndrome was associated with worse in-hospital outcomes, and an increased risk of heart failure. Examining the metabolic syndrome criteria independently, the researchers found that hyperglycemia (high blood glucose level) was a major determining factor associated with severe heart failure.

"Our study showed the high prevalence of metabolic syndrome among patients with AMI and highlights the detrimental impact of metabolic syndrome on short-term outcomes, particularly heart failure," the authors write. "Finally, our study suggests that, among metabolic syndrome components, hyperglycemia has the strongest relation to increased incidence of congestive heart failure in patients with metabolic syndrome and MI. Given the ever-increasing prevalence of metabolic syndrome worldwide, this finding has important clinical implications and confirms the importance of evaluating glycemic control during the acute phase of MI."

Liver X Receptors Key To Diet-Dependent Differences in Blood Lipid Levels

Fri, 13 May 2005 20:25:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Pennsylvania School of Medicine have discovered that a molecule found in liver cells is an important link in explaining the relationship among diet, lipid levels in blood, and atherosclerosis. The research team surmises that drugs targeted at the liver may one day help lower elevated lipids and battle cardiovascular disease. Mitchell Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism at Penn, and colleagues report their findings in the May 2005 issue of Cell Metabolism.

The high-cholesterol, high-fat so-called Western diet has accelerated an epidemic of atherosclerotic cardiovascular disease, the leading cause of death in industrialized nations. And, understanding interactions between genes and the reality of what most people eat are increasingly recognized as critical for effective treatment.

Molecules found in the nucleus of liver cells called LXRs (for Liver X Receptors) have emerged in the last few years as crucial regulators of cholesterol and lipid metabolism. The conventional wisdomborne out of drug-development studies done before this paperwas that LXRs are good in terms of decreasing atherosclerosis and bad in terms of increased triglycerides, explains Lazar. Indeed, although LXR-based experimental drugs, which dramatically increase LXR activity throughout the body, reduce cholesterol levels in the blood, they also lead to high levels of triglycerides.

Surmising that a targeted approach might work better, the researchers used transgenic mice engineered to have an excess of LXR in their liver only, which gave the mice high levels of cholesterol and an increased risk of heart disease. They found that LXR, which senses fat in the liver, could adjust the consequences of eating a high-fat Western diet.

The team found that the increased liver LXR worsened levels of cholesterol and triglycerides in mice fed a normal, low-fat diet. However, surprisingly, when the same transgenic mice with increased LXR were fed a high-fat/high-cholesterol diet, similar in composition to a standard Western diet, their blood cholesterol and triglyceride levels actually improved. Furthermore, the mice were protected from the atherosclerotic cardiovascular disease that normally results from this diet. However, the beneficial effect of the increased LXR levels was lost when mice were treated with the experimental drug.

The researchers concluded that increased expression of LXR in the liver is beneficial in a body full of natural molecules that bind to the LXR receptor, which are generated by the Western diet, but not when on a low-fat, healthy diet. However, this benefit is lost when a potent drug is added to the system. The reason is that a different set of target genes is turned on by this synthetic molecule, as opposed to the natural molecule, says Lazar. Were saying, maybe what we need are drugs that mimic the natural ligand rather than a sledgehammer like the potent pharmaceutical drugs that too powerfully activate LXRs throughout the body. The hope is that these will decrease cholesterol without increasing triglycerides.

One of the main questions facing the study of complex metabolic diseases is, if two people eat a high-fat diet, why does one persons cholesterol go up but the others does not. If we find natural variations in people in the amount of LXR in their livers, this may help explain this conundrum of the difference in susceptibility to high cholesterol and heart disease, depending on diet, says Lazar. The answer is genetics. Our work suggests that one of the new genetic factors to pay attention to is the amount of LXR in the liver.

Positive Clinical Trial Results of Novel Anti-Obesity Compound

Thu, 12 May 2005 18:09:00 PST

( from http://www.rxpgnews.com ) Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced today positive top-line results from its Phase 2 clinical trial of APD356, Arena's orally administered, internally discovered drug candidate for the treatment of obesity. Over the 28 day treatment period, there was a highly statistically significant (p=.0002) average weight loss of 2.9 pounds in patients taking the 15 mg dose of APD356 versus 0.7 pounds for the placebo group. APD356 was generally well tolerated at all doses investigated in the trial. APD356 is a selective agonist of 5-HT2C serotonin receptors, which are located in the hypothalamus, an area of the brain known to play an important role in regulating food intake and metabolism.

"The prevalence of obesity has increased substantially in recent years and has reached alarming rates. Obesity is a serious health risk and is associated with several conditions, including diabetes, stroke and heart disease. Patients and their physicians need novel methods to treat obesity," stated Steven Smith, M.D., Principal Investigator and Associate Professor of the Pennington Biomedical Research Center. "The results of this trial are very supportive of further study and provide hope that obese individuals could have a new therapeutic option in the future to help control their weight in an effective, safe and controlled manner."

This Phase 2 clinical trial of APD356 was a randomized, double-blinded, multiple-dose study examining 352 obese volunteers at 24 clinical sites in the United States. The trial was to enroll otherwise healthy male and female patients with a body mass index (BMI) of between 30 and 45. Patients were randomized into four groups to compare doses of 1, 5 and 15 mg of APD356 versus placebo. The trial evaluated safety and weight loss after oral administration of APD356 once daily for 28 days. The trial protocol provided that patients should maintain their normal diet and level of activity, but required that patients abstain from consuming alcohol. In addition to standard safety evaluations, patients were assessed by echocardiogram upon enrollment, and were scheduled for follow-up echocardiograms at 29 and 90 days after receiving their first dose.

Patient demographic characteristics at baseline were well balanced across treatment groups. Eighty percent of participants were women, 55% were Caucasian, 25% African-American and 18% Hispanic. At baseline, the average age was 40 years, the average weight was 223 pounds (range 158-468 pounds), and the average BMI was 36.

The primary efficacy endpoint of the Phase 2 study was a reduction in weight in patients completing the 28 day treatment period (Day 29). Compared to placebo, treatment with APD356 was associated with a highly statistically significant average weight loss of 2.9 pounds in the 15 mg group versus 0.7 pounds in the placebo group. No statistically significant weight loss was observed in the 1 mg or 5 mg groups. Similar results were observed in the intent-to-treat, last observation carried forward (LOCF) analysis. The table below summarizes the mean weight change for all patients completing the study in each group.

Group Mean Weight Change p value
from Baseline
(pounds) (relative to placebo)

Placebo (n=71) -0.7 --
1.0 mg (n=75) -0.7 Not statistically significant
5.0 mg (n=72) -0.9 Not statistically significant
15.0 mg (n=69) -2.9 p = 0.0002

APD356 was generally well tolerated at all doses investigated, and there were no serious adverse events in the trial. Events that occurred in 5% or more of patients in a treatment group are listed below.

Event Placebo 1 mg 5 mg 15 mg

Nausea 3.5% 5.6% 5.6% 6.9%
Nasopharyngitis 5.8% 4.4% 3.4% 1.1%
Headache 14.0% 15.6% 7.9% 20.7%
Cough 1.2% 5.6% 2.2% 1.1%

There was no apparent drug effect on the heart as assessed by Day 29 echocardiograms. Post day 29 echocardiograms are pending.

"All of us at Arena are excited with these results, and we would like to thank all the patients, clinicians and nurses participating in our study. We intend to use these results to build on our APD356 clinical program and soon initiate a Phase 2b trial enrolling approximately 300 to 400 patients in a study designed to investigate the efficacy and safety of APD356 over a three- month period," stated Jack Lief, Arena's President and CEO. "In addition to supporting the continued development of APD356, these top-line results should strongly support our partnering efforts and further validate our research and development capabilities."

Oleoyl estrone in Phase Ib Trial

Wed, 04 May 2005 21:51:00 PST

( from http://www.rxpgnews.com ) Manhattan Pharmaceuticals, Inc. ("Manhattan" OTCBB: MHTT), has concluded its Phase Ia trial and begun patient dosing in the Phase Ib trial to evaluate the safety and tolerability of defined doses of orally administered Oleoyl estrone (OE) in obese adults. Like the Phase Ia trial, the Phase Ib trial will be conducted in Basel, Switzerland under Swiss Medic Approval.

The Phase Ia trial, conducted with the approval of the U.S. Food & Drug Administration (FDA) and SwissMedic, the Swiss regulatory authority, was a single-dose, dose-escalation trial that evaluated six cohorts of six patients, randomized 2:1 study drug to placebo. Manhattan is currently reviewing and analyzing the results of the trial, which will ultimately be used to obtain approval to move forward with Phase II studies.

The recently commenced Phase Ib trial is a repeat-dose, dose-escalation trial that will evaluate four cohorts of six patients each, randomized 2:1 study drug to placebo. Results from this study will also be used, in conjunction with extensive preclinical work, to establish the protocol and obtain approval from the US FDA to begin Phase II clinical trials.

"We are pleased that OE's clinical development is proceeding according to our anticipated timeline," said Douglas Abel, CEO of Manhattan Pharmaceuticals. "This Phase I trial will provide needed additional information about OE's tolerability and move us closer to securing the approvals necessary to bring this treatment to a patient population clearly in need of an alternative to the current therapeutics."

Oleoyl estrone - Targeting the Obesity Epidemic

Oleoyl estrone is believed to be a signaling molecule that acts on the hypothalamus to communicate satiety. It is hypothesized that, in healthy individuals, levels of naturally occurring OE are related to the size of the body's fat stores, while in obese individuals circulating OE levels are lower than would be expected for the level of body fat. Orally administered formulations of OE has been demonstrated, in extensive preclinical animal studies, to cause significant weight loss and reduced caloric consumption without the need for dietary modifications.

In such studies, OE appears to be safe and effective without side effects or evidence of rebound weight gain after treatment was stopped. The Company believes that OE may prove to be a safe and effective treatment for obesity, representing a significant advantage over currently available anti-obesity medications.

Manhattan believes OE could help address the obesity epidemic - one of the world's top health concerns. Nearly two-thirds of the U.S. adult population is estimated to be overweight and at least half of these are clinically obese. Though there are currently two FDA approved therapeutics on the market for the long-term treatment of obesity, market penetration remains low, possibly as a result of the modest efficacy (an average of 8-10% weight loss in the first year), and side effects reported with use of these treatment options.

Manhattan has reported favorable, peer-reviewed preclinical safety and pharmacokinetic data regarding OE at the 2004 annual meetings of the European Congress on Obesity, and the North American Association for the Study of Obesity.

Effect of Plant Extracts on Metabolic Syndrome to be Investigated

Wed, 04 May 2005 18:17:00 PST

( from http://www.rxpgnews.com ) Rutgers University plant scientists are truly into something hot. They are working with a research laboratory named for the late Tabasco® Pepper Sauce heir, John S. McIlhenny, and built with a gift from the trust he established, the Coypu Foundation. The lab is part of the Pennington Biomedical Research Center, a campus of the Louisiana State University system. At this facility, researchers collaborating with Rutgers colleagues will investigate whether plant extracts can cut risk factors for heart disease, stroke, diabetes or other serious illnesses.

An $8 million, five-year botanical research grant from the National Institutes of Health (NIH) will enable Rutgers plant scientists to collaborate with Pennington researchers in forming the NIH Center for Botanicals and Metabolic Syndrome, one of five newly funded NIH dietary supplement research centers.

Center researchers will study the effects of plant extracts on metabolic syndrome, a collection of risk factors that predispose a person to potentially life-threatening disorders. Common risk factors include obesity, hypertension and high insulin levels. In combination, the risk factors can produce a whole the syndrome that is truly greater than the sum of its parts.

This center is one of five NIH dietary supplement research centers, jointly funded by the National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements, focusing on studies of botanical products.

With $1.4 million from the NIH grant and matching funds from Rutgers, research will be conducted in the laboratory of Ilya Raskin at the Biotechnology Center for Agriculture and the Environment on Rutgers' Cook College campus.

"We will grow most of the plants and use biochemistry to isolate the bioactive compounds," said Raskin, professor of plant science at Rutgers, The State University of New Jersey, and associate director of the new NIH center. "We will determine which chemical compounds in the plants have therapeutic potential and, with the assistance of the LSU Agricultural Center, learn how to best grow them to produce the highest concentrations of the compounds."

The "Tabasco contingent," led by Pennington's Dr. William Cefalu, NIH center director, will do the medical testing and, in the third and fourth years of the study, conduct the human clinical trials. Pennington, the largest academically based nutrition research center in the world, conducts both clinical and basic research and is acknowledged to be the premier institution in its field.

"Metabolic syndrome represents one of the most important public health problems facing our society as the prevalence is reaching epidemic proportions worldwide," Cefalu said.

The treatment of metabolic syndrome is a particularly promising area for botanicals because the complex syndrome has many different targets. Most botanicals derive their effectiveness from a mixture of active molecules, acting in concert. Multiple agents attacking multiple targets simultaneously present decided advantages over conventional drugs which are each based on one compound that produces one action, Raskin explained. "When you have a complex condition like metabolic syndrome in which so many things can go wrong, it will not be possible to deal with all of them with just one single chemical," he said.

Unexpected Discovery About Iron Overload

Thu, 28 Apr 2005 20:56:00 PST

( from http://www.rxpgnews.com ) UAB and international scientists studying iron-overload disorders have made the unexpected discovery that Asians and Pacific Islanders have the highest levels of iron in their blood of all racial/ethnic groups who were screened.

Individuals who develop hemochromatosis/iron overload absorb an excessive amount of iron from food and supplements ingested. The abnormality affects many people worldwide, is prevalent in the South, and sometimes causes organ damage when severe iron deposition occurs due to inadequate control of iron absorption by the small intestine.

The first major report of findings in the five-year, 100,000-person study will be published tomorrow, April 28, in The New England Journal of Medicine (NEJM). The University of Alabama at Birmingham received $3.1 million of study funds to screen 20,000 people for the group of disorders called hemochromatosis and iron overload.

Ronald T. Acton, Ph.D., professor of microbiology and director of the UAB Immunogenetics Program, is principal investigator for the Birmingham Field Center that did the screening. James C. Barton, M.D., director of the Southern Iron Disorders Center and UAB clinical professor of medicine, is co-principal investigator. They exceeded the goal of screening 10,000 African-Americans and 10,000 whites for blood iron levels or the presence of mutations in a gene, called the HFE gene, which evidence suggests regulates iron absorption.

Hemochromatosis and iron overload are easily treatable if diagnosed early, but the simple blood test that could detect these conditions is not performed as part of routine medical exams, said Acton. Delaying treatment the weekly removal of a pint of blood by phlebotomy can permit the progressive accumulation of iron deposits in target organs that may result in complications such as cirrhosis of the liver, liver cancer, arthritis, diabetes, impotence and heart failure.

The finding that Asians and Pacific Islanders have high levels of iron in the blood is surprising because they also have the lowest prevalence of the particular gene mutation that is found in Caucasians with the typical form of hemochromatosis, he said. This may mean that the Asians and Pacific Islanders have a different genetic mutation that has not yet been discovered, or that they do not, for some reason, develop hemochromatosis/iron overload despite their high blood levels of iron.

He said that the NEJM paper is the first report from analysis of the massive data arising from the study, called the Hemochromatosis and Iron Overload Screening (HEIRS) Study. The study is funded by the National Heart, Lung and Blood Institute and the National Human Genome Research Institute.

The other HEIRS Study Field Centers were located at University of California, Irvine; London Health Sciences Centre, Ontario, Canada; Howard University, Washington, D.C.; and Kaiser Permanente Center for Health Research (Oregon and Hawaii). Wake Forest University in Winston-Salem, N.C. coordinated the Study, and the Studys Central Laboratory is located at the University of Minnesota in Minneapolis.

At the beginning of the study in 2000, it was known that most cases of hemochromatosis in Caucasians resulted from common mutations in the HFE gene, first discovered in 1996. At that time, little was known about the causes of iron overload in other racial/ethnic groups.

Major findings of the study include:

* Caucasians had the highest prevalence of persons who had two copies of the C282Y mutation of the HFE gene (4.4 per 1,000 people).

* Prevalence of two copies of the C282Y mutation of the HFE gene in other racial/ethnic groups were: Native Americans (1.1 per 1,000), Hispanics (2.7 per 10,000), African-Americans (1.4 per 10,000), Pacific Islanders (1.2 per 10,000) and Asians (3.9 per 10 million).

* Most participants who had two copies of the C282Y mutation of the HFE gene also had elevated levels of iron in their blood.

* Men who had two copies of the C282Y mutation of the HFE gene were more likely to report a history of liver disease than participants without HFE mutations.

Our findings in Caucasians confirm reports from previous smaller studies, said Acton. Our findings in non-Caucasians help everyone understand the prevalence of these conditions in other racial/ethnic groups.

He added that many white Alabamians have Celtic origins, with some counties reporting Irish ancestry in 17 percent of the population. The hemochromatosis C282Y mutation is thought to have occurred among Celtic or Scandinavian populations 1,500-3,000 years ago, and the mutation may have helped them survive iron-poor diets.

Hemochromatosis or iron overload occur in 0.3-0.5 percent of white persons of northern, central, and western European descent. In fact, a health-screening program conducted by Barton and Acton at an Alabama forest products mill detected the disorder in 0.39 percent of all white participants, and 0.53 percent of white men.

Acton and Barton said they hope that results of the study will prompt more primary care physicians to consider hemochromatosis and iron overload as a diagnosis. Nationwide studies indicate it takes an average of nine years and three physicians to obtain a correct diagnosis, partly because physicians incorrectly believe that such disorders are rare, or that they affect only older men. A previous UAB study found that primary care physicians provided fewer than 70 percent correct responses about screening at-risk populations for hemochromatosis, iron overload, and associated abnormalities.

As the HEIRS Study shows, iron overload was mistakenly believed to be a disorder that is limited to Caucasians, said Acton. He, Barton, and others have begun studying the role of iron overload and HFE mutations in the development of type 2 diabetes in persons of various racial/ethnic groups.

Reversible Metabolic Hibernation Induced Successfully

Tue, 26 Apr 2005 19:02:00 PST

( from http://www.rxpgnews.com ) Scientists at Fred Hutchinson Cancer Research Center have, for the first time, induced a state of reversible metabolic hibernation in mice. This achievement, the first demonstration of "hibernation on demand" in a mammal, ultimately could lead to new ways to treat cancer and prevent injury and death from insufficient blood supply to organs and tissues.

"We are, in essence, temporarily converting mice from warm-blooded to cold-blooded creatures, which is exactly the same thing that happens naturally when mammals hibernate," said lead investigator Mark Roth, Ph.D., whose findings will be published in the April 22 issue of Science.

"We think this may be a latent ability that all mammals have potentially even humans and we're just harnessing it and turning it on and off, inducing a state of hibernation on demand," said Roth, a member of Fred Hutchinson's Basic Sciences Division.

During a hibernation-like state, cellular activity slows to a near standstill, which reduces dramatically an organism's need for oxygen. If such temporary metabolic inactivity and subsequent freedom from oxygen dependence could be replicated in humans, it could help buy time for critically ill patients on organ-transplant lists and in operating rooms, ERs and battlefields, Roth said.

"Manipulating this metabolic mechanism for clinical benefit potentially could revolutionize treatment for a host of human ills related to ischemia, or damage to living tissue from lack of oxygen," said Roth, also an affiliate professor of biochemistry at the University of Washington School of Medicine.

Collaborators on the research included first author Eric Blackstone, a graduate research assistant in Roth's laboratory and a member of the joint Fred Hutchinson/University of Washington Molecular and Cellular Biology Program; and co-author Mike Morrison, Ph.D., a staff scientist in Roth's lab.

Clinical applications of induced metabolic hibernation could include treating severe blood-loss injury, hypothermia, malignant fever, cardiac arrest and stroke.

The potential medical benefits also include improving cancer treatment by allowing patients to tolerate higher radiation doses without damaging healthy tissue. Cancer cells, Roth explained, aren't dependent on oxygen to grow. As a result, they are more resistant to radiation than surrounding healthy cells, which need oxygen to live. Roth hypothesizes that temporarily eliminating oxygen dependence in healthy cells could make them a less-vulnerable target for radiation and chemotherapy and thus spare normal tissue during high-dose cancer therapy.

"Right now in most forms of cancer treatment we're killing off the normal cells long before we're killing off the tumor cells. By inducing metabolic hibernation in healthy tissue we'd at least level the playing field," he said. The delivery of such treatment could be as simple as an intravenous infusion of saline solution mixed with trace amounts of an agent that would interfere with the body's ability to use oxygen, Roth said.

Using oxygen deprivation to depress metabolic activity also might extend the amount of time that organs and tissues could be preserved outside the body prior to transplantation, Roth said. Yet another potential application of oxygen deprivation would include accelerating wound healing in patients, such as diabetics, whose ability to do so is compromised. This could reduce the number of amputations caused by irreparable tissue damage from wounds that won't heal. A wound to the skin allows the entry of oxygen, which initiates cell death. In healthy people, cell death subsides when a clot forms, which allows the healing process to begin. Exposing a diabetic's clot-resistant wound to an oxygen-free environment would speed the healing process.

While the notion of putting a human or a human organ into an oxygen-free state of biological limbo and then reversing the process at will with no ill effects may sound like science fiction, dozens of documented cases exist of humans surviving prolonged hibernation-like states with no lingering physical or neurological damage. For example:

* In May 1999, a female Norwegian skier was rescued after submersion in icy water for more than an hour. When rescued she was clinically dead with no heartbeat, no respiration, and her body temperature had fallen to 57 degrees Fahrenheit (normal is 98.6 F). She was resuscitated and since has made a good physical and mental recovery.

* More recently, in February 2001, Canadian toddler Erika Nordby made headlines around the world and a complete recovery after she wandered outside at night and nearly froze to death. Before she was resuscitated her heart had stopped beating for two hours and her temperature had plunged to 61 F.

"Understanding the connections between random instances of seemingly miraculous, unexplained survival in so-called clinically dead humans and our ability to induce and reverse metabolic quiescence in model organisms could have dramatic implications for medical care," Roth said. "In the end I suspect there will be clinical benefits and it will change the way medicine is practiced, because we will, in short, be able to buy patients time."

In the Science paper, Roth and colleagues report inducing a state of clinical torpor in mice for up to six hours before restoring their normal metabolic function and activity.

They achieved this by placing the mice in a chamber filled with normal room air laced with 80 parts per million of hydrogen sulfide, a chemical normally produced in humans and animals that is believed to help regulate body temperature and metabolic activity.

Within minutes of breathing the hydrogen sulfide and room-air cocktail, the mice stopped moving and appeared to lose consciousness, their respiration dropped from the normal 120 breaths per minute to fewer than 10 breaths per minute, and their core temperature dropped from the normal 37 degrees Celsius to as low as 11 C, depending on the controlled ambient temperature within the chamber.

"We have, on demand, reversibly demonstrated the widest range of metabolic flexibility that anyone has ever seen in a non-hibernating animal," Roth said.

"The cool thing about this gas we're using, hydrogen sulfide, is that it isn't something manufactured that we're taking down from a shelf it isn't 'better living through chemistry' it's simply an agent that all of us make in our bodies all the time to buffer our metabolic flexibility. It's what allows our core temperature to stay at 98.6 degrees, regardless of whether we're in Alaska or Tahiti," Roth said.

In addition to mice, Roth and colleagues in previously published work have demonstrated the ability to metabolically arrest and subsequently re-animate such model organisms as yeast and worms, as well as the embryos of fruit flies and zebrafish.

In each case they achieved metabolic suspension through oxygen deprivation caused by exposure to gases such as hydrogen sulfide and carbon monoxide. Known as oxygen mimetics, these chemicals are very similar to oxygen at the molecular level and so bind to many of the same receptor sites. As a result, they compete for and interfere with the body's ability to use oxygen for energy production - a process within the cell's power-generating machinery called oxidative phosphorylation. The inhibition of this function, in turn, is what the researchers believe causes the organism to shut down metabolically and enter a hibernation-like state. In each case, upon re-exposure to normal room air, the organisms quickly regained normal function and metabolic activity with no long-term negative effects.

If Roth and colleagues are able to replicate these findings in larger animal models, they foresee the first clinical use of this technology in humans could involve treating people suffering from severe fevers of unknown origin. Currently, when a person comes to an ER with such a fever they run the risk of brain-damaging seizures during the crucial time it takes to diagnose the bacterial or viral cause and administer the proper antibiotic.

"Here's a patient group, quite commonly found in emergency rooms around the country, who would do well if they could just have their core body temperature taken down in order to buy them time until the pathology reports come back and they can get on the right course of treatment," Roth said. "Today, physicians have no way of dealing with uncontrolled fever other than literally putting people on ice. Well, we believe we know how to flip the breaker on the patient's furnace; if they have a fever, we believe we know how to stop it on a dime." Roth anticipates that such clinical trials in humans could be under way within about five years.

Simple Actions Wipe Out Huge Higher Heart Risks For Asian Diabetics

Mon, 25 Apr 2005 19:41:00 PST

( from http://www.rxpgnews.com ) New research, to be revealed on Tuesday 26th of April at the launch of the University of Warwick Medical School's new Clinical Sciences Research Institute at the University Hospital campus at Walsgrave in Coventry, has shown that very simple interventions to target the health care of UK Asian diabetics can almost wipe out the 40% higher risks of heart disease linked to diabetes in that community.

Warwick Medical School researcher Dr Paul O'Hare will use the launch of the Clinical Sciences Research Institute to outline that diabetes is four times more common in the UK Asian population than it is among Caucasians. Onset of diabetes can also be over a decade earlier among Asian patients and Asian diabetics face a much higher risk of renal and heart complications leading to a 40% higher mortality rate compared with Caucasians.

The researchers also point out that, on top of these increased diabetes risk faced by the Asian population, cultural and communication differences make health care delivery much more challenging for this community group.

The researchers studied what the effect would be of a special effort to target and reach out to the Asian community on the issue of diabetic and related health care. This effort attempted to overcome the health care delivery challenges posed by that community and tried to address the substantially increased health risks they faced in this case. They observed the results of this special pilot package of diabetes health care outreach to over 500 UK Asians in Coventry and Birmingham. The simple package included the use of multi-lingual Asian health workers led by a community diabetes specialist nurse.

The researchers found this approach provided a number of benefits but one of the most significant was an average drop in blood pressure of around 4mmHg in the Asian patients - research has shown that such a drop in blood pressure leads to a 35% reduction in the risk of heart disease. The simple tools of this new pilot outreach effort to the UK Asians had thus, in just one parameter, almost completely wiped out the huge 40% increased risk of heart disease traditionally faced by that community.

The researchers have now scaled their research up to a study of around 2000 people that will consider a wide range of possible diabetes-related health effects and implications for the NHS.

New Erchonia Laser Revolutionizes Liposuction

Sun, 24 Apr 2005 08:07:00 PST

( from http://www.rxpgnews.com ) The Stern Center for Aesthetic Surgery, PC, a Bellevue based practice focused on staying on the cutting edge of new cosmetic surgery advances announced their use of the new Erchonia laser during liposuction.

The Stern Center for Aesthetic Surgery, PC, led by Dr. Fredric A. Stern, uses the Erchonia 4L laser, the first and only low-level laser approved by the FDA for use during liposuction.

The painless laser treatment is administered a few minutes prior to liposuction, and works by liquefying the fat. As a result, fat removal is made easier and quicker, and there is less post-op pain and bruising, with a speedier recovery time. Less pain medication is required for this procedure compared to traditional liposuction methods.

The FDA approved the laser based on the results of an IRB approved, multi-center, double blind randomized study. The comparison between the actively treated patients and the placebo-treated patients resulted in an impressive difference between groups in the emulsification of fat, ease of extraction, amount of swelling, and degree of pain.

Use of the Erchonia laser during liposuction offers our patients tremendous benefits, and will revolutionize the procedure, making liposuction as close to a no down time cosmetic surgical procedure as there is. We are excited to incorporate this new FDA approved device into our practice, states Dr. Stern.

Dr. Fredric A. Stern has been in practice since 1987, and established The Stern Center for Aesthetic Surgery, PC, in Bellevue in 1997. Erchonia was founded in 1996 and is dedicated to advancing the science of health through the development of superior bio-medical laser products.

Excess Deaths Associated with Underweight, Overweight and Obesity

Thu, 21 Apr 2005 17:20:00 PST

( from http://www.rxpgnews.com ) Using data collected from the most recent NHANES, Katherine Flegal, Ph.D., CDCs National Center for Health Statistics, and her co-authors from CDC and the National Cancer Institute, part of the National Institutes of Health, found that both obesity and being underweight are associated with excess deaths when compared with the normal weight population.

The study found:

* There were 112,000 more deaths than expected in 2000 among obese individuals (BMI of 30 or higher).

* Underweight individuals (BMI of less than 18.5) had a higher risk of death with nearly 34,000 more deaths than expected.

* Most of the excess deaths among the underweight occurred in people age 70 or older. Among the obese, the increased risk of death was most pronounced among people younger than 70.

* Being overweight (BMI of 25-29.9) was not associated with excess mortality. The study found that 87,000 fewer deaths than expected were associated with being overweight.

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