Cardiovascular Disease (CVD) Risk and Prevention in Early Glucose Intolerance
Condition: Impaired Glucose Tolerance; Prediabetic State
MeSH terms: Cardiovascular Diseases; Glucose Intolerance; Prediabetic State
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether cardiovascular disease (CVD) risk markers,
      β-cell function, and insulin sensitivity can be improved by targeting mechanisms of both
      diabetes and CVD - using an antioxidant, an angiotensin II receptor blocker (ARB), or an
      anti-inflammatory agent - in patients with impaired glucose tolerance (IGT) in a randomized,
      controlled trial.
    

Detailed description: 
      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.

      The purpose of Aim 2 of this study is to determine whether a "high" blood sugar level
      measured one hour after drinking a standard high-sugar drink (1-hour blood sugar level) is
      associated with an increased risk of heart disease even in individuals who have no evidence
      of diabetes or pre-diabetes. Seventy-five volunteers with normal glucose tolerance (normal
      blood sugars after ingesting a standard high-sugar drink) will be recruited from the SIGT
      study, as well as 15 subjects with impaired glucose tolerance and 15 with diabetes. The
      subjects with normal glucose tolerance will be grouped into those with "low", "middle", and
      "high" 1-hour blood sugar levels. All subjects will undergo medical testing (as in Aim 1
      above) to determine their risk of heart disease. Test results of subjects with "low",
      "middle", and "high" 1-hour blood sugar levels will be compared against one another, as well
      as against those of subjects with IGT and diabetes. If subjects with normal glucose tolerance
      but "high" 1-hour blood sugar levels are found to have increased risk for heart disease
      compared to those with "low" 1-hour blood sugar levels, then the 1-hour blood sugar levels
      may provide important information regarding an increased risk of heart disease even in
      individuals with normal glucose tolerance but "high" 1-hour blood sugar levels - a population
      which otherwise would not be identified with the current standard tests used for the
      diagnosis of diabetes and pre-diabetes.

      Over 40 million Americans have pre-diabetes (impaired glucose tolerance), which is associated
      with an increased risk of the development of both diabetes and heart disease. Findings from
      these studies will provide important insights into the pathways that lead to the development
      of heart disease related to pre-diabetes, prevention of heart disease in the pre-diabetic
      population, and identification of individuals at high risk for heart disease earlier in their
      natural history - even before the onset of pre-diabetes.
    

Intervention name(s): Aspirin; Alpha lipoic acid; Olmesartan; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 325 mg PO QD; 600 mg PO BID; 40 mg PO QD; Identical placebo for each active comparator:
placebo aspirin 325 mg PO QD; placebo for alpha lipoic acid 600 mg PO BID; placebo for olmesartan 40 mg PO QD
Other intervention name(s): Bayer aspirin; Benicar
Intervention MeSH terms: Aspirin; Thioctic Acid; Olmesartan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Prediabetic state; Cardiovascular disease; Diabetes; Glucose intolerance