April 2003 - American children whose genetic roots strongly reach back to Africa are less sensitive to insulin-a factor important in the development of type 2 diabetes-than those whose ancestors hailed heavily from Europe, according to study results recently released.
Rather than relying on broad categories of race, such as black or white, researchers in diabetes and obesity from the Keck School of Medicine of USC and the University of Alabama at Birmingham analyzed a group of children for 20 key genetic markers found far more often in those of African descent than those of European descent. They found that the more African-origin markers in children's genetic makeup, the less their bodies responded to insulin-and the more insulin in their blood.
Study results were published in the April issue of the journal Diabetes.
Medical researchers have long known that diabetes disproportionately afflicts black communities. But by using specific genetic markers of ancestry, the UAB and Keck School team is moving beyond general concepts of race and racial groupings to better understand how genes influence the development of disease.
"We have previously shown that African-American children are more insulin-resistant, but prior to this study, we lacked evidence suggesting a genetic basis of this effect," says Michael I. Goran, Ph.D., professor of preventive medicine and physiology and biophysics at the Keck School and a study coauthor. "With these results, we have evidence to suggest that at least part of the different profile in African Americans may be intrinsic rather than due to environmental factors."
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"Knowing that genes may play a role in ethnic differences in risk for type 2 diabetes may influence how physicians treat their patients," adds study co-author Barbara A. Gower, Ph.D., associate professor of nutrition sciences at UAB. "In particular, they may want to emphasize the importance of a healthy lifestyle to their African-American patients."
Gower indicated that follow-up analyses with individual markers will be a first step toward identifying specific genes associated with insulin secretion or action.
Researchers conducted their study in a group of 125 Alabama children between ages 5 and 16 who identified themselves either as African American or European American.
They tested for numerous insulin-related measures and body fat and obtained DNA samples. They also gathered information about children's socioeconomic status.
The researchers looked for 20 specific sequences of genetic code that are found more frequently in people of African descent than in those of European descent. This analysis measures the individuals' "African admixture," a term for the relative proportion of their genetic make-up that reflects African origin. Pennsylvania State University researchers came up with the genetic panel and analyzed the DNA.
Looking at the group as a whole, the more African-origin genetic markers found in the children, the less sensitive the children were to insulin.
Insulin works in this way: Normally, after a meal, the body breaks down carbohydrates into glucose, or sugar, in the blood. That signals the pancreas to secrete insulin, because insulin helps the body's cells pick up the glucose and convert it to energy. But when cells become less sensitive to insulin, as they gradually do in type 2 diabetes, they cannot absorb glucose as well as they should and the sugar remains in the blood.
The proportion of African-origin markers found in the children also was linked to higher fasting insulin (levels of insulin in the blood between meals) and greater acute insulin response (levels of insulin in response to glucose from food).
Socioeconomic status, meanwhile, only was related to acute insulin response. The lower the socioeconomic level of children's families, the greater the acute insulin response.
Researchers say the study suggests that genetic factors may influence the pancreas' function, the ability of the liver to get rid of insulin, or both. Because social and environmental factors also appear to play a role, though, identifying the specific factors at fault also will be important in understanding and preventing the racial and ethnic disparities seen in type 2 diabetes.
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In the future, the team hopes to use additional genetic markers to better characterize people's genetic makeup and eventually track down the specific genes that are associated with insulin sensitivity and acute insulin response.
The National Institutes of Health sponsored the research. Barbara A. Gower, Jos� R. Fern�ndez, T. Mark Beasley, Mark D. Shriver, and Michael I. Goran, "Using Genetic Admixture to Explain Racial Differences in Insulin-Related Phenotypes," Diabetes. April 2003, Vol. 52, No. 4.
Source: University of Southern California
