RESEARCH DESIGN AND METHODS -In the present study, we compared insulin sensitivity as assessed by a 4-h euglycemic ( 5 mmol/l) hyperinsulinemic ( 300 pmol/l) clamp with HOMA in 115 subjects with various degrees of glucose tolerance and insulin sensitivity.R E S U LT S -We found a strong correlation between clamp-measured total glucose disposal and HOMA-estimated insulin sensitivity (r = 0.820, P 0.0001), with no substantial diff e rences between men (r = 0.800) and women (r = 0.796), younger (aged 50 years, r = 0.832) and older (r = 0.800) subjects, nonobese (BMI 27 kg/m 2 , r = 0.800) and obese (r = 0.765) subjects, nondiabetic (r = 0.754) and diabetic (r = 0.695) subjects, and normotensive ( r = 0.786) and hypertensive (r = 0.762) subjects. Also, we found good agre ement between the two methods in the categorization of subjects according to insulin sensitivity (weighted k = 0.63).C O N C L U S I O N S -We conclude that the HOMA can be reliably used in large-scale or epidemiological studies in which only a fasting blood sample is available to assess insulin sensitivity. r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s Diabetes Care

OBJECTIVE -To evaluate whether homeostasis model assessment-estimated insulin resistance (HOMA-IR) is an independent predictor of cardiovascular disease (CVD) in type 2 diabetes.RESEARCH DESIGN AND METHODS -Conventional CVD risk factors (sex, age, smoking, plasma lipids, blood pressure, and metabolic control) and insulin resistance (estimated by HOMA) were evaluated at baseline in 1,326 patients with type 2 diabetes examined within the Verona Diabetes Complications Study. At baseline and after a mean follow-up of 4.5 years, CVD was assessed by medical history, physical examination, electrocardiography, and echo-Doppler of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow-up were carefully scrutinized to identify cardiovascular deaths. In statistical analyses, CVD was an aggregate end point including both fatal and nonfatal coronary, cerebrovascular, and peripheral vascular disease as well as ischemic electrocardiographic abnormalities and vascular lesions identified by echo-Doppler.RESULTS -At baseline, 441 subjects were coded positive for CVD (prevalent cases). Incident cases numbered 126. Multiple logistic regression analyses showed that, along with sex, age, smoking, HDL/total cholesterol ratio, and hypertension, HOMA-IR was an independent predictor of both prevalent and incident CVD. A 1-unit increase in (log)HOMA-IR value was associated with an odds ratio for prevalent CVD at baseline of 1.31 (95% CI 1.10 -1.56, P ϭ 0.002) and for incident CVD during follow-up of 1.56 (95% CI 1.14 -2.12, P Ͻ 0.001).CONCLUSIONS -HOMA-IR is an independent predictor of CVD in type 2 diabetes. The improvement of insulin resistance might have beneficial effects not only on glucose control but also on CVD in patients with type 2 diabetes.

In Type 2 diabetes, the presence of the Metabolic Syndrome is associated with an almost 5-fold increase in CVD risk.

These results confirm a reduced vasodilatory capacity in diabetes mellitus, with a more marked alteration in microalbuminuric diabetic subjects. This reliable, noninvasive evaluation of arterial function is particularly useful for early diagnosis of vascular involvement.

ACE inhibition improves endothelium-dependent vasodilation in the femoral artery of normotensive microalbuminuric type 1 diabetic patients. Captopril also ameliorates endothelium-independent vasodilation, possibly through its sulfhydryl donor properties. These results may be of pathophysiological relevance to prevent cardiovascular complications in these patients.