Diabetes, Lipoproteins and Accelerated Vascular Disease

Sponsor
Columbia University (Other)
Overall Status
Completed
CT.gov ID
NCT00005479
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
164
1
156
1.1

Study Details

Study Description

Brief 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.

Study Design

Study Type:
Observational
Actual Enrollment :
164 participants
Observational Model:
Case-Control
Time Perspective:
Cross-Sectional
Official Title:
Measures of Postprandial Lipoproteins Are Not Associated With Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus
Study Start Date :
Sep 1, 1996
Actual Primary Completion Date :
Aug 1, 2001
Actual Study Completion Date :
Sep 1, 2009

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    35 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion criteria

    • Patients with type 2 diabetes mellitus (DM), defined by medical record diagnosis, fasting glucose >140 mg/dl, or the use of diabetes medications

    • Had a myocardial infarction (MI) any time in the past, a coronary angiogram within the previous year, or an exercise perfusion scan (stress thallium study) within one year

    • Patients with CAD group, defined by the following criteria: documented prior MI, PTCA/stent, CABG, or >75% stenosis in any vessel by coronary angiography.

    • Patients without CAD group, defined as: the absence of a prior MI and <50% stenosis in all vessels by coronary angiography within the past year, or the combination of a normal exercise perfusion scan and the absence of a prior MI or any interventional cardiac procedures.

    Exclusion criteria

    • MI or cardiac procedures within the past 3 months

    • Diagnoses of cancer, severe congestive heart failure (ejection fraction < 20%), kidney or liver disease, pancreatitis, other gastrointestinal conditions,

    • Laboratory values of creatinine levels > 1.3, abnormal liver function tests, abnormal CBC, fasting TG > 400 mg/dl, urine protein > 2+ on urinalysis or > 1000 mg/24 h, abnormal thyroid function tests, body mass index (BMI) > 34 for men and > 37 for women or BMI < 20 for both sexes

    • Age < 35 or > 75 years

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Columbia University New York New York United States 10032

    Sponsors and Collaborators

    • Columbia University
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Henry Ginsberg, MD, Herbert and Florence Irving Professor of Medicine; Director, Irv, Dept Medicine Preventive Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Columbia University
    ClinicalTrials.gov Identifier:
    NCT00005479
    Other Study ID Numbers:
    • CUMC ID unknown (4963)
    • P01HL057217
    First Posted:
    May 26, 2000
    Last Update Posted:
    Dec 28, 2015
    Last Verified:
    Dec 1, 2015

    Study Results

    No Results Posted as of Dec 28, 2015