Insulin resistance and carotid atherosclerosis in patients with type 2 diabetes

Objective: Insulin resistance may provide a crucial link between type 2 diabetes and cardiovascular disease. However, it is still unclear whether insulin resistance itself or hyperinsulinemia is independently associated with subclinical atherosclerosis. We hypothesized that insulin resistance, but not hyperinsulinemia, would be associated with carotid atherosclerosis in patients with type 2 diabetes. Methods: We examined 2471 patients with type 2 diabetes, consecutively enrolled in Huh Diabetes Center. Insulin sensitivity was directly assessed by a rate constant for plasma glucose disappearance (Kitt) using short insulin tolerance test. Fasting insulin levels were used as a marker of hyperinsulinemia. Both carotid arteries were examined by B-mode ultrasound. Carotid atherosclerosis was defined by having a clearly isolated focal plaque or mean carotid intima-media thickness (IMT) ≥1.1 mm. Results: In multiple regression models, insulin sensitivity index (Kitt) but not hyperinsulinemia was significantly associated with carotid IMT adjusting for known risk factors such as age, sex, BMI, smoking, systolic pressure, HDL and LDL cholesterol. One standard deviation decrease in Kitt was associated with 0.046 mm increase in carotid IMT (p = 0.015). Furthermore, odds ratio for carotid atherosclerosis was 1.43 (95% CI: 1.10, 1.86) in type 2 diabetic patients with insulin resistance (lowest quartile of insulin sensitivity) adjusting for known risk factors. The results were consistent in all subgroups stratified by sex, age, smoking and hypertension. Conclusion: Insulin resistance measured by short insulin tolerance test, but not hyperinsulinemia, is independently associated with carotid atherosclerosis in patients with type 2 diabetes.