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Generational risk of diabetes

To test their hypothesis that environmental influences experienced by the father can be passed down to the next generation in the form of changed epigenetic information, Rando and colleagues fed different diets to two groups of male mice. The first group received a standard diet, while the second received a low-protein diet. To control for maternal influences, all females were fed the same, standard diet. Rando and colleagues observed that offspring of the mice fed the low-protein diet exhibited a marked increase in the genes responsible for lipid and cholesterol synthesis in comparison to offspring of the control group fed the standard diet.

These observations are consistent with epidemiological data from two well-known human studies suggesting that parental diet has an effect on the health of offspring. One of these studies, called the Överkalix Cohort Study, conducted among residents of an isolated community in the far northeast of Sweden, found that poor diet during the paternal grandfather’s adolescence increased the risk of diabetes, obesity and cardiovascular disease in second-generation offspring. However, because these studies are retrospective and involve dynamic populations, they are unable to completely account for all social and economic variables. “Our study begins to rule out the possibility that social and economic factors, or differences in the DNA sequence, may be contributing to what we’re seeing,” said Rando. “It strongly implicates epigenetic inheritance as a contributing factor to changes in gene function.”

The results also have implications for our understanding of evolutionary processes, says Hans A. Hofmann, PhD, associate professor of integrative biology at the University of Texas at Austin and a co-author of the study. “It has increasingly become clear in recent years that mothers can endow their offspring with information about the environment, for instance via early experience and maternal factors, and thus make them possibly better adapted to environmental change. Our results show that offspring can inherit such acquired characters even from a parent they have never directly interacted with, which provides a novel mechanism through which natural selection could act in the course of evolution.” Such a process was first proposed by the early evolutionist Jean-Baptiste Lamarck, but then dismissed by 20th century biologists when genetic evidence seemed to provide a sufficient explanation.

Taken together, these studies suggest that a better understanding of the environment experienced by our parents, such as diet, may be a useful clinical tool for assessing disease risk for illnesses, such as diabetes or heart disease. “We often look at a patient’s behavior and their genes to assess risk,” said Rando. “If the patient smokes, they are going to be at an increased risk for cancer. If the family has a long history of heart disease, they might carry a gene that makes them more susceptible to heart disease. But we’re more than just our genes and our behavior. Knowing what environmental factors your parents experienced is also important.”

The next step for Rando and colleagues is to explore how and why this genetic reprogramming is being transmitted from generation to generation. “We don’t know why these genes are being reprogrammed or how, precisely, that information is being passed down to the next generation,” said Rando. “It’s consistent with the idea that when parents go hungry, it’s best for offspring to hoard calories, however, it’s not clear if these changes are advantageous in the context of a low-protein diet.”

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Change lifestyle to reduce diabetes

Experts have suggested that an intensive lifestyle intervention helps individuals with type 2 diabetes lose weight and keep it off, along with improving fitness, control of blood glucose levels and risk factors for cardiovascular disease. Improving blood glucose control and cardiovascular risk factors in patients with type 2 diabetes is critical in preventing long-term complications of the disease.

The Look AHEAD (Action for Health in Diabetes) Research Group conducted a multicenter randomized clinical trial comparing the effects of an intensive lifestyle intervention to diabetes support and education among 5,145 overweight individuals with type 2 diabetes.

Of these, 2,570 were assigned to the lifestyle intervention, a combination of diet modification and physical activity designed to induce a 7 percent weight loss in the first year and maintain it in subsequent years. The 2,575 individuals assigned to the diabetes support and education group were invited to three group sessions each year. On average, across the four-year period, individuals in the lifestyle intervention group lost a significantly larger percentage of their weight than did those in the diabetes support group.

They also experienced greater improvements in fitness, hemoglobin A1c level (a measure of blood glucose), blood pressure and levels of high-density lipoprotein. Individuals in the diabetes support group, on the other hand, experienced greater reductions in low-density lipoprotein, owing to greater use of cholesterol-lowering medications in this group.

The report was published in the September 27 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

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