Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk study

OBJECTIVE:Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. APPROACH AND RESULTS: We studied a European cohort of 525 men and 655 women (mean age, 44 ± 8 years) free of conditions known to affect carotid wall (diabetes mellitus, hypertension, and dyslipidemia). All subjects received an oral glucose tolerance test, a euglycemic hyperinsulinemic clamp (M/I as a measure of insulin sensitivity), and B-mode carotid ultrasound. In 833 participants (380 men), the carotid ultrasound was repeated after 3 years. In men, baseline intima-media thickness in the common carotid artery (CCA-IMT) was significantly higher (P<0.05) in the lowest M/I tertile, whereas in women CCA-IMT was higher (P<0.0005) in the highest fasting plasma glucose tertile (after adjustment for established risk factors). In multiple regression models, with CCA-IMT as the dependent variable and with risk factors and univariate metabolic correlates as independent variables, circulating free fatty acids and the leptin:adiponectin ratio replaced M/I as independent metabolic determinants of CCA-IMT in men. The strongest metabolic determinant of CCA-IMT in women was fasting plasma glucose. Three-year CCA-IMT changes were not associated with any cardio-metabolic risk factor. CONCLUSIONS: In young-to-middle aged apparently healthy people, the association of CCA-IMT with insulin sensitivity and its metabolic correlates differs between men and women. Lower insulin sensitivity is associated with higher IMT only in men; this association seems to be mediated by circulating free fatty acids and adipocytokines. In women, CCA-IMT is independently associated with fasting plasma glucose.