Researchers Look To Our Ancestors For Diabetic Genetic Connection: Throughout history, the root causes of complex diseases like obesity and type 2 diabetes have been very hard to identify. In recent years, the diseases happen where genes and the environment collide making it very hard to see the genetic culprit behind them. But now, researchers at the Stanford University School of Medicine have identified genetic discrepancies in a hormone involved in the secretion of insulin, a molecule that occurs in more humans than others and is known to control blood sugars.

The human populations that share this new discrepancy were thought to have appeared in history 2,000 to 12,000 years ago. They had higher fasting levels of blood glucose then the traditional gene that is found today. When a body has high blood glucose levels that are connected with diabetes, the body is unable to produce or respond to insulin.

With this new study, scientists may be able to understand human metabolism, which occurred between the transitions from human hunters/gatherers to a more agriculturally based civilization. It could also help doctors track diabetes in patients to allow them to see which individuals are more likely to develop diabetes and can help provide an early development in treatment and therapies alike.

Sheau Yu “Teddy” Hsu, PhD, an assistant professor of obstetrics and gynecology and one of the senior author behind this study had this to say,”These studies are fascinating because it shows how much the selection process has affected human energy-balance regulation in just a few thousand years and how complex it could be for the future practice of personalized medicine.”

Hsu and his colleagues at Chang Gung Memorial Hospital in Taiwan and Texas A&M University first identified 207 genetic regions, which have been connected with obesity and diabetes. These genetic regions were then looked into further to see which ones had started to increase when humans departed from Africa more than 60,000 years ago. Fifty-nine genetic regions became of great interest that occurred in 30 percent of people associated with the HapMap Project. The HapMap Project is a worldwide survey of the genetic differences in mixed populations.

Five genes with different genetics occurred more frequently in Asians and Europeans. “We thought GIP was the most interesting because the newly selected form occurs in about 50 percent of people from Europe or Asia, but in only about 5 percent of Africans. That indicates this gene is highly adaptable to new environments,” said Hsu.

Hsu and his team identified 3 separate changes in the region of GIP, the DNA neighbor to the GIP gene, which affects when and how it is decoded into protein, which reduces the levels of the hormone itself. The three separate changes also appeared with another alteration in the coding region causing the result of a different form of protein, which is degraded slowly in human blood.

Hsu said. “So now we know there are two different forms of the protein, which allowed one form to be selected in one population, and the other in a different population, but we still needed to show that these variants led to phenotypic differences in modern humans.”

Hsu and his colleagues next focused their study on pregnant women. Out of 123 East Asian pregnant women, those who held two copies of the newly developed alternate had considerably lower levels of GIP circulating in their blood. They were also at a considerably increased risk to have fasting blood glucose levels that surpassed the suggested amount of 140 mg/dL. The finding many help doctors in determining which pregnant women may be at more risk of developing gestational diabetes. It may also shine some light on how our ancestors adapted to the changing world.

“Like other humans at the time, the Eurasian population really had to fight for survival.” Now we’re starting to pinpoint how they did that on a molecular level. These gene variants, and the resulting higher blood sugar levels it fostered, may have helped women maintain successful pregnancies in the face of the inevitable famines that occur in an agriculturally based society. Now, in a more food-secure environment, variations in GIP could contribute to the development of diabetes or obesity.” said Hsu.