Insulin sensitivity in subjects with type 2 diabetes - Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study

OBJECTIVE - Among nondiabetic subjects, insulin resistance has been associa ted with increased cardiovascular risk factors, including dyslipidemia, hyp ertension, impaired fibrinolysis, and coagulation. Less is known about the relationship between insulin resistance and cardiovascular risk factors in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS - to examine this issue, we determined insulin sensitivity (S-1) in 479 type 2 diabetic subjects by minimal model analyses of frequently sampled intravenous glucose tolerance tests in the Insulin R esistance Atherosclerosis Study (IRAS), a large multicenter study of insuli n sensitivity and cardiovascular disease in African-Americans, Hispanics, a nd non-Hispanic whites. We defined insulin-sensitive subjects as having S-1 greater than or equal to 1.61 X 10(-4) min(-1) . mu U-1 . ml(-1) (above me dian in nondiabetic subjects of all ethnic groups in the IRAS). Using this definition, only 37 type 2 diabetic subjects were insulin sensitive, and th e remaining 442 were insulin resistant. RESULTS - After adjustment for age, sex, ethnicity and clinic, insulin resi stance was significantly correlated with total triglycerides, VLDL choleste rol, VLDL triglyceride, fibrinogen, PAI-1, and fasting glucose, and was inv ersely correlated with HDL cholesterol level and LDL size. Carotid intimal- medial thickness was greater in insulin-resistant than in insulin-sensitive subjects, but this difference was nor statistically significant. After fur ther adjustment for waist circumference (marker of visceral adiposity), ins ulin resistant subjects continued to have higher plasminogen activator inhi bitor 1 and VLDL triglyceride levels, lower HDL cholesterol levels, and sma ller LDL particle size than did insulin-sensitive subjects. After further a djustment for fasting glucose levels, these results were very similar. CONCLUSIONS - We conclude that insulin-resistant type 2 diabetic subjects h ave more atherogenic cardiovascular risk factor profiles than insulin-sensi tive type 2 diabetic subjects and that this is only partially related to in creased obesity and an adverse body fat distribution.