Diabetes, Lipoproteins and Accelerated Vascular Disease
Condition: Cardiovascular Diseases; Heart Diseases; Coronary Disease; Atherosclerosis; Carotid Artery Diseases; Diabetes Mellitus, Non-insulin Dependent; Diabetes Mellitus
MeSH terms: Carotid Artery Diseases; Cardiovascular Diseases; Heart Diseases; Atherosclerosis; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Observational

Summary: 
      To better understand the excess cardiovascular disease associated with diabetes mellitus.
    

Detailed description: 
      BACKGROUND:

      Diabetes mellitus is associated with a 2-4 fold increase in risk for atherosclerotic
      cardiovascular disease. Atherosclerotic cardiovascular disease, particularly coronary artery
      disease, is the leading cause of death in diabetics. The study was a subproject within a
      program project grant, with Henry Ginsberg as principal investigator. The program project was
      part of an institute-initiated study on The Etiology of Excess Cardiovascular Disease in
      Diabetes Mellitus. The initiative originated after discussions between NHLBI and the Juvenile
      Diabetes Foundation International (JDFI). The Request for Applications (RFA) was originally
      issued in October 1994 and resulted in the award of one grant The RFA was reissued in
      December 1995 and resulted in the awarding of five program project grants, the one under
      discussion among them.

      DESIGN NARRATIVE:

      The study, subproject 3 within a program project grant, was entitled Atherogenic Triglyceride
      Rich Lipoproteins in Diabetes. The subproject examined the atherogenicity of
      hypertriglyceridemia in subjects with non-insulin dependent diabetes mellitus (NIDDM).
      Subproject 3 tested hypotheses concerning the impact of the size and number of
      triglyceride-rich lipoproteins (TGRL) on risk for atherosclerotic cardiovascular disease
      (ASCVD) in several human populations. A case-control study of diabetics with or without
      coronary artery disease determined if TGRL size and number differed between the groups. In
      this study, Whites, Blacks and Hispanics with documented coronary artery disease or with less
      than 50 percent coronary stenosis by angiography were recruited. The hypothesis was tested
      that increased apoB in small TGRL was associated with coronary artery disease. Fasting and
      postprandial blood samples were obtained for measurement of TGRL apoB level, TGRL TG:apoB
      ratio, the amount of apoB in apoE-rich TGRL, and retinyl palmitate clearance. Allelic
      differences in the apoB, apoE, LPL, and apoCIII genes were examined for effects on the size
      and number of TGRL: specific hypotheses were tested regarding the impact of these alleles.

      TGRL size and number were also compared in diabetics with and without carotid atherosclerosis
      in the Atherosclerosis Risk in Communities (ARIC) study, in Sioux and Pima Indian tribes that
      differed in ASCVD rates, and in Blacks, Whites and Hispanics with a range of insulin levels
      and insulin resistance in the Insulin Resistance and Atherosclerosis Study (IRAS). These
      studies served both to confirm findings in the case-control study and to provide the
      opportunity to investigate diverse populations. The collaboration with IRAS allowed
      determination of the effects of insulin resistance and insulin secretory capacity on TGRL
      size and number. Finally, experiments with cultured endothelial cells were performed to
      determine if small TGRL could cause endothelial dysfunction. PMI-1 and VCAM-1 were markers of
      TGRL effects. In the case-control study, plasma PMI and VCAM-1 were measured to examine their
      relationship to coronary artery disease and to TGRL size and number.

      Dollars awarded were estimated based on the CRISP assignment of $173,249 dollars in FY 1996
      for Subproject 3. This was approximately 25 percent of the total dollars awarded and was used
      to estimated committed dollars.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Individuals with type 2 diabetes mellitus (DM) with or without coronary artery disease
        (CAD)