title: Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk study.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Pisa, Italy. m.kozakova@int.med.unipi.it
authors.forename: Michaela
authors.initials: M
authors.lastname: Kozakova
authors.forename: Andrea
authors.initials: A
authors.lastname: Natali
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Dekker
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Nielsen
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000328:Adult; D017677:Age Distribution; D001786:Blood Glucose / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D008078:Cholesterol, LDL / Q000378:metabolism; D015331:Cohort Studies; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D017678:Sex Distribution
chemical_list: D054392:Adipokines; D001786:Blood Glucose; D008078:Cholesterol, LDL; D005227:Fatty Acids
keywords: adipokine; atherosclerosis; carotid intima-media thickness; fatty acids; glucose