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Type 2 Diabetes
Are We Closer to Knowing "Why?"

by Wayne Clark

Notably, a relationship has been observed between the risk of diabetes associated with low birth weight and the risk of later development of diabetes in the father. This could indicate a genetic link in support of the fetal origins hypothesis.

Given the genetic link, prevention of diabetes even in the presence of the predisposition is a major research goal. Clinical trials have demonstrated that the number of people who develop diabetes can be reduced by 25% to 62% over a period of three to six years. The concept is to reduce body fat or to counter the effect that excess fat has on insulin resistance.

The Finnish Diabetes Study in Finland and the Diabetes Prevention Program in the United States showed that reducing caloric intake and increasing physical activity can reduce the risk that people with impaired glucose tolerance (sometimes called prediabetes) will go on to develop diabetes. The “Xenical in the Prevention of Diabetes in Obese Subjects” study combined this kind of intensive lifestyle modification with the weight-loss drug orlistat and produced a 37% relative risk reduction for diabetes compared with lifestyle intervention alone. Several studies using the diabetes drugs known as glitazones (Actos and Avandia), metformin, and acarbose (brand name Precose) have also resulted in significant risk reductions.

There is another way to reduce body fat, and to reduce it dramatically: bariatric surgery. A trial in Australia randomly assigned study participants with recently diagnosed Type 2 diabetes to either lifestyle modification or laparoscopic adjustable gastric banding (commonly referred to as the Lap-Band procedure). After two years, 73% of the people who had had the Lap-Band surgery were diabetes- free, compared with just 13% of those in the lifestyle group.

An even more dramatic result has been reported in studies of the impact of the Roux-en-Y gastric bypass procedure on diabetes and obesity. Some 84% of people who have the surgery have complete remission of diabetes following the procedure. What’s more, a third of those people go into remission before they even leave the hospital, and most of the rest are diabetes-free within a month.

“It’s true that gastric bypass surgery causes diabetes to remit long before it would be expected to do so as a result of the weight loss,” Dr. Cummings says. “Also, people who lose weight due to bypass surgery have better glucose tolerance later on than do those who have lost equivalent weight due to diet or banding.”

Scientists speculate that the bypass surgery brings other factors into play beyond the loss of weight. One theory is that after bypass, food is brought to the far end of the small intestine more quickly, where it stimulates production of the hormone glucagon-like peptide 1 (GLP-1). GLP-1 stimulates the secretion of insulin and may also send signals of satiety (fullness) to the brain. This “antidiabetic” effect could account for the rapid resolution of diabetes. Another possibility is that the procedure impairs the production of the hormone ghrelin in the stomach. Ghrelin is a hunger hormone and has the opposite effect of GLP-1.

This is a treatment, or arguably a cure, for existing Type 2 diabetes. The exciting possibility, however, is the potential for using the procedure to prevent diabetes from developing in obese people who have insulin resistance. Dr. Cummings explains that early in the development of diabetes, the beta cells are overwhelmed and eventually lose the ability to secrete the insulin they’re still producing. However, the cells are not destroyed, and significant weight loss can bring them back to normal functioning.

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