CVD Risk and Prevention in Early Glucose Intolerance

Diabetes is a common, major health problem in the United States, and it significantly increases the risk of developing heart disease, which is the leading cause of death. Research studies have shown that the risk of heart disease is increased, even in the "pre-diabetes" or impaired glucose tolerance (IGT) stage, before the onset of true diabetes. While many studies have shown that aggressive management of diabetes lowers the risk of heart disease, at the present time, it is not known how best to treat patients with impaired glucose tolerance (pre-diabetes) to prevent the development of heart disease. It is also not known where in the range of blood sugar levels risk begins to increase. The purpose of this study is to determine:

• whether medications, which target pathways involved in the development of heart disease, can decrease the risk of heart disease in individuals with impaired glucose tolerance; and
• whether a "high" blood sugar level measured one hour after drinking a standard high-sugar drink is associated with an increased risk of heart disease even in individuals who have no evidence of diabetes or pre-diabetes.

The purpose of Aim 1 of this study is to determine whether medications, which target pathways involved in the development of heart disease, can decrease the risk of heart disease in individuals with impaired glucose tolerance. One hundred-twenty volunteers with impaired glucose tolerance and 30 volunteers with normal glucose tolerance (normal blood sugars after ingesting a standard high-sugar drink) will be recruited from the "Screening for Impaired Glucose Tolerance" (SIGT) study. The 30 volunteers with normal glucose tolerance will not take any study medication, but will undergo medical testing to determine their risk of heart disease at the beginning of the study, after which their participation in the study will be complete. The 120 volunteers with impaired glucose tolerance will be randomly assigned to one of four medications to be taken over a one-year period:

• alpha lipoic acid (an antioxidant, dietary supplement);
• olmesartan (a drug used to treat high blood pressure);
• aspirin (an anti-inflammatory drug); and
• placebo (an inactive, "dummy" pill).

Subjects with impaired glucose tolerance will undergo medical testing to determine their risk of heart disease at the beginning of the study (before beginning study medications), after 3 months of intervention, and again at the end of the study (12 months after enrollment). Test results will be compared between the subjects taking each of the active medications and those taking placebo, to determine if the medications lead to a significant reduction in the risk for the development of heart disease. The medical tests used in this study are currently used in medical practice, and include blood and urine specimens, ultrasound testing of the artery at the arm, and an insulin sensitivity test (test of how effectively the body uses sugar). All visits and tests will be conducted in the General Clinical Research Centers of Emory University Hospital and Grady Memorial Hospital.