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Randomized Controlled Trial Comparative Study Clinical Trial
Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT).
- Hanna Bloomfield Rubins, Sander J Robins, Dorothea Collins, David B Nelson, Marshall B Elam, Ernst J Schaefer, Fred H Faas, and James W Anderson.
- Section of General Internal Medicine (111O), Veterans Affairs Medical Center, 1 Veterans Dr, Minneapolis, MN 55417. bloom013@umn.edu
- Arch Intern Med. 2002 Dec 9;162(22):2597-604.
BackgroundDiabetes mellitus, impaired fasting glucose level, or insulin resistance are associated with increased risk of cardiovascular disease.ObjectivesTo determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes.MethodsSubgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, a randomized controlled trial that enrolled 2531 men with coronary heart disease (CHD), a high-density lipoprotein cholesterol level of 40 mg/dL or less (=1.04 mmol/L), and a low-density lipoprotein cholesterol level of 140 mg/dL or less (=3.63 mmol/L). Subjects received either gemfibrozil (1200 mg/d) or matching placebo and were followed up for an average of 5.1 years. In this article, we report the composite end point (CHD death, stroke, or myocardial infarction).ResultsCompared with those with a normal fasting glucose level, risk was increased in subjects with known diabetes (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.44-2.43; P =.001) and those with newly diagnosed diabetes (HR, 1.72; 95% CI, 1.10-2.68; P =.02). In persons without diabetes, a fasting plasma insulin level of 39 micro U/mL or greater (>/=271 pmol/L) was associated with a 31% increased risk of events (P =.03). Gemfibrozil was effective in persons with diabetes (risk reduction for composite end point, 32%; P =.004). The reduction in CHD death was 41% (HR, 0.59; 95% CI, 0.39-0.91; P =.02). Among individuals without diabetes, gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile (risk reduction, 35%; P =.04).ConclusionIn men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.
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