USA - Is there an "obesity paradox" in diabetes?

NEW YORK - Obesity and diabetes might not be the double whammy you'd expect, according to a fresh look at older studies.

Surprisingly, researchers found that overweight and obese people who get diagnosed with the blood sugar disorder tend to live longer than their leaner peers.

This so-called "obesity paradox" has been observed before in chronic diseases like heart and kidney failure, said Mercedes R. Carnethon of the Feinberg School of Medicine at Northwestern University in Chicago.

But that doesn't mean you should start downing ice cream and other high-calorie foods if you just found out you have diabetes, Carnethon told Reuters Health. Nor does it mean that padding your waist is a good way to improve your prognosis before you get the disease.

In fact, it's probably not that excessive pounds are protective, said Carnethon, but rather that lean people who get diabetes are somehow predisposed to worse health.

"Perhaps those individuals are somehow genetically loaded to develop diabetes and have higher mortality," she said. "A normal-weight person who has diabetes has an extremely high mortality rate."

The new findings are based on data from five earlier studies that tracked people over time to identify risk factors for heart disease. More than 2,600 participants developed type 2 diabetes during the studies, and 12 per cent of them had a normal weight when they got the diagnosis.

The death rate was 1.5 per cent per year among overweight and obese people, compared to 2.8 per cent per year among their trimmer peers.

After accounting for several risk factors for heart disease - including age, blood pressure, high cholesterol and smoking - lean people were more than twice as likely to die at any given point as heavier people. The same held true for deaths caused by heart disease, which is linked to obesity.

"It was a little bit unexpected to see that," said Carnethon.

One potential limitation of the study is that the researchers couldn't always account for how much people smoked, which might explain part of the results.

It's also possible that a few people might have been diagnosed with diabetes outside of the studies and been told to slim down by their own doctor before they were seen by the study researchers. That could also have contributed to the findings, although Carnethon said the effect would be small.

She added that it's not clear how to best treat normal-weight people with type 2 diabetes, although weight training seems preferable over cardio exercise.

Older people and people of Asian descent are more likely to be normal-weight when diagnosed with diabetes, and Carnethon stressed that doctors need to take the disorder extra seriously when it's not accompanied by obesity.

"These findings do apply to a growing segment of the population," she said.

SOURCE: bit.ly/O0uT3Q Journal of the American Medical Association, online August 7, 2012.

Reuters

USA - More evidence for longevity pathway

New research reinforces the claim that resveratrol—a compound found in plants and food groups, notably red wine—prolongs lifespan and health-span by boosting the activity of mitochondria, the cell's energy supplier.

"The results were surprisingly clear," said David Sinclair, a professor of genetics at Harvard Medical School and the study's senior author. "Without the mitochondria-boosting gene SIRT1, resveratrol does not work."

The findings are to be published May 1 in the journal Cell Metabolism.

Over the last decade, Sinclair and colleagues including Leonard Guarente at Massachusetts Institute of Technology have published a body of research describing how resveratrol improves energy production and overall health in cells by activating a class of genes called sirtuins that are integral to mitochondrial function.

The cell's power supplier, mitochondria are essential not just for longevity but for overall health.

Sinclair and colleagues had studied sirtuins in a variety of model organisms: yeast, worms, flies and mice. For the first three organisms they were able to thoroughly knock out SIRT1 and show that cells lacking the gene don't respond to resveratrol. But no one had been able to demonstrate the effect in mice, which die at birth without the SIRT1 gene.

In order to solve this obstacle, Nathan Price and Ana Gomes, graduate students in the Sinclair lab, spent three years engineering a new mouse model. These mice, seemingly normal in every way, were designed so that SIRT1 would systemically switch off when the mice were given the drug Tamoxifen.

"This is a drug inducible, whole body deletion of a gene," said Sinclair. "This is something that's rarely been done so efficiently. Moving forward, this mouse model will be valuable to many different labs for other areas of research."

The results were plain: when mice were given low doses of resveratrol after SIRT1 was disabled, the researchers found no discernable improvement in mitochondrial function. In contrast, the mice with normal SIRT1 function given resveratrol showed dramatic increases in energy.

While the tantalizing prospect of increasing healthy lifespan has made resveratrol the subject of intense scientific interest, some researchers have questioned the link to SIRT1. A competing theory holds that resveratrol may work by activating a separate energy pathway called AMPK, which, while also related to mitochondria, does not involve sirtuin genes.

In their new paper, Sinclair and colleagues report that when mice lacking SIRT1 were given low doses of resveratrol, AMPK was unaffected. When doses were significantly increased in these mice, AMPK was activated, but still no benefit to mitochondrial function resulted.

"Resveratrol is a dirty molecule, so when you give very, very high doses, many things could be happening," said Sinclair. "It's standard when you study molecules that you use the lowest dose that gives you an effect because of the risk of hitting other things if you use too much. But for the downstream benefits on energy, you still need SIRT1. Our paper shows that SIRT1 is front and center for any dose of resveratrol."

More information: Cell Metabolism, May, 2012, Vol 15, No 5

Provided by Harvard Medical School (news : web)

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