The diabetes genotype causes a predisposition for glucose intolerance. The development of type 2 diabetes is influenced by environmental factors, some clearly defined, others less so. The Nurses Health Survey showed the expected positive associations between obesity and lack of physical activity in the development of type 2 diabetes, but also protection related to abstinence from smoking and to moderate alcohol use (24). The protective effect of alcohol has been found in other studies, and was confirmed in a recent meta-analysis (25). Also obscure is a reported association between type 2 diabetes and sleep deprivation (26), and a protective effect of caffeine (27). More understandable are the numerous studies showing associations between risk of type 2 diabetes and high calorie diets, physical inactivity, and our modern lifestyle in general.

These predisposing factors share an ability to negatively impact glucose homeostasis through worsening of insulin resistance or impairment of B-cell function. Superimposing these factors onto a genetically compromised system augments the risk of hyperglycemia. The rapid emergence of these disadvantageous environmental factors is causing the worldwide diabetes epidemic. This concept was highlighted many years ago by nomadic or farm-based populations that moved to urban environments, followed by an explosion of diabetes, typically with profound obesity: Pima Indians in the Southwest United States, Saharan nomadic tribes, and Australian Aborigines are well-known examples. Studies that show reversal of the diabetes after members of these populations return to their prior way of life are particularly notable (28). A recent example of the effect of population shifts is the rapidly rising incidence of type 2 diabetes in China and India as people flood to the cities; there is a 0.1-0.2% incidence of diabetes in rural parts of China as opposed to more than 5% for city dwellers. Perhaps the most distressing example of rapid change is the rising incidence of obesity in children in the US. As many as 20% of US children are now obese, and they are developing all of the elements of the metabolic syndrome: insulin resistance, hypertension, hyperlipidemia, and glucose intolerance (29). Additionally gestational diabetes has doubled in prevalence in the U.S. over the last decade (30).

An obvious conclusion is that a return to a healthier lifestyle should reverse the diabetes trend. Indeed, many studies have shown diet and exercise markedly decrease the onset of diabetes in persons with IGT (2,31,32). The difficulty, of course, is trying to get people to change their habits. In addition, we are lacking long term studies of lifestyle modification in terms of a protective effect against cardiovascular disease.

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