HOLLI W. HAYNIE

Dr. Samuel Dagogo-Jack monitors a study participant’s energy expenditure with the Metabolic CART equipment.

What factors cause one person to develop diabetes while someone else with a similar background never acquires the disorder?

Why is it that African-Americans develop diabetes at a twice the rate of Caucasians?

An innovative study at the University of Tennessee intends to answer those questions.

Last year, the University of Tennessee Health Science Center (UTHSC) was awarded a $2.9 million grant from the National Institutes of Health (NIH), under the leadership of Dr. Samuel Dagogo-Jack, program director of the UTHSC division of endocrinology, diabetes and metabolism, to identify the subtle mechanisms that deteriorate the metabolism long before diabetes occurs.

In particular, Dagogo-Jack has honed in on pre-diabetes, the health condition also known as impaired glucose tolerance.

Pre-diabetes is like the holding station for full blown diabetes, representing a score on the blood glucose test that lies between normal and diabetes. Almost everyone who is eventually diagnosed with diabetes, explained Dagogo-Jack, has spent some time at the pre-diabetic state.

According to the American Diabetes Association (ADA), pre-diabetes is a condition with no symptoms; 54 million people in the United States over age 20 are pre-diabetic. Current medical practice does not require people to be screened for the condition. However, knowing someone has pre-diabetes immediately identifies them as being at high risk for future diabetes.

The rate of progression from pre-diabetes to diabetes is approximately 10 percent a year. In five years, half of the pre-diabetic population has converted, and in a decade, almost every pre-diabetic has moved on to full-blown diabetes.

“We focused on pre-diabetes because recent research shows that individuals with pre-diabetes can be treated along with non-drug approaches and be redeemed,” explained Dagogo-Jack. “We have studies that show effects as much as a 60 to 65 percent reduction in the risk of progression from pre-diabetes to diabetes.”

Even more compelling was new evidence in the Diabetes Prevention Program study which observed, most surprisingly, noted Dagogo-Jack, that Caucasians, African-Americans and all other minority groups (which also suffer from diabetes disproportionately compared to Caucasians), progressed to diabetes at exactly similar rates once they reached the pre-diabetic stage. There were no two-fold differences between black or white.

“We didn’t see a shred of ethnic difference,” Dagogo-Jack said, adding that the information led him to an epiphany. “Perhaps once you get pre-diabetes, you’re locked into future diabetes so firmly that white or black no longer makes a difference, and if that is the case, perhaps the driving force for the eventual higher rates of diabetes in African-Americans must have been initiated much earlier, prior to the stage of pre-diabetes.”

The NIH had been soliciting research proposals, Dagogo-Jack explained, aimed at unraveling the biological, pathobiological and physiological explanations often quoted as racial/ethnic differences in the diabetes risk. While these differences have been known for more than half a century, the exact mechanisms and timing of the ethnic and racial differences in the development of diabetes are not well understood. The NIH chose the UTHSC Dagogo-Jack study as the most likely one to offer new insights and discoveries relevant to the ethnic disparity.

The study will compare African-Americans and Caucasians who have one or both parents with type 2 diabetes. Currently, the study is just over one-third full and still actively seeking eligible applicants.

Potential participants must not have had a diagnosis of pre-diabetes or diabetes. Over a five year period, explained Dagogo-Jack, researchers will repeatedly assess changes in body composition; diet and exercise habits; insulin sensitivity, resistance and secretion; fat cell derived hormones, as well as a variety of risk predictors.

His team is using innovative tools to measure and calculate the various factors, including the new metabolic CART system that measures total energy expenditure. Using this comprehensive machine, patients lay down on a bed and breathe into tubes for 10 to 15 minutes.

“With these measurements, we can see whether those who change their glucose control without gaining weight may have had some other subtle alterations in their hormonal metabolic milieu and whether it was a critical decrease in their ability to burn calories,” he explained.

Dagogo-Jack also explained that if, for example, 200 African-Americans and 200 Caucasians were both born into families with diabetes, that means they both have the genetic rift. If both groups are enrolled at a stage when their blood glucose is perfectly normal and they are tested repeatedly to find scientific markers using the latest biochemical and genetic measurements, “which one of these measurements predicts a change from perfect glucose to just five to 10 points higher?” asked Dagogo-Jack.

“What triggers a person that was born normal to have the metabolism deteriorate, their glucose controlling powers wane, the regulatory mechanisms diffuse and one day wake up and they are no longer normal, [but] now is in the stage of pre-diabetes?” Dagogo-Jack posited. “We want to be the first to crack open the mysteries in the transition from perfectly normal glucose to pre-diabetes, and if we understand what makes the body fail to regulate blood glucose in the normal range [and] we understood the determinants of the earliest stage of escape from normal glucose, we would discover something that would be helpful to all races and ethnicities.”

Dagogo-Jack is confident that by studying the earlier mechanisms for glucose abnormalities, his team will discover the biology of early glucose escape and that the ethnic disparity is occurring much earlier than pre-diabetes. The research team plans to communicate an abstract in March to the Southern Society for Clinical Investigation based on screening data.

“We’re pretty confident that this study in Memphis, when successfully completed, is probably going to place Memphis more brightly on the map in human endocrinology diabetes studies,” added Dagogo-Jack, “and it will be quoted a lot and often.”

Eligibility for Consideration and Contact Info

• Must be Caucasian or African American
• Age 18-65
• One or both parents have type 2 diabetes (do not have to be living)
• Cannot have a diagnosis of diabetes

There are other criteria that must be met which will be discussed after initial consideration.
Contact info: Local call 901-448-5299, out of area code call toll free 877-707-1222



November 2007