title: Insulin resistant young subjects at risk of accelerated atherosclerosis exhibit a marked reduction in peripheral endothelial function early in life but not differences in intima-media thickness.
abstract: Reduced bio-availability of nitric oxide leading to disturbed flow mediated (endothelial dependent) vasodilation (FMD) has been shown to be an early functional abnormality of the vascular system in insulin resistant individuals and other subjects at high risk for accelerated atherosclerosis. In addition, an increase of the intima-media thickness (IMT) is regarded as an early marker of morphological alterations of the vessel wall. Whether endothelial dysfunction (ED) is evident already at an early stage when morphological changes of the vessel wall are not apparent is still an open question. We, therefore, examined IMT and peripheral endothelial function in a group of young insulin resistant subjects in a cross-sectional study and compared these results with a metabolically healthy (insulin sensitive) control group. We measured IMT (distal common carotid arteries), endothelium-dependent and endothelium-independent vasodilation (flow mediated and glyceroltrinitrate induced vasodilation of the brachial artery) non-invasively with high resolution ultrasound (13 MHz) in 91 young normoglycemic subjects (40/51 M/F, median: 31 years, range 18-50 years). Insulin sensitivity was measured with a euglycemic, hyperinsulinemic glucose clamp. Despite a marked reduction in flow-mediated vasodilation in insulin resistant (IR) subjects (FMD: median 3.4%, range -4.0 to 12.5 in IR versus 6.6%, range -1.2 to 20.1% in insulin sensitive subjects; P = 0.017), there was no difference in endothelial independent vasodilation (16.3%, range 5.7-41.0% versus 16.1%, range 0.5-39.2%) and in IMT (0.50 mm, range 0.39-0.66 and 0.51, 0.40-0.70 mm, respectively). These data suggest that ED can be detected very early in the life of insulin resistant subjects whereas no significant structural changes, indicated by a thickening of the intima-media layer, could be found. We therefore conclude that for identification of subjects with a high risk for accelerated atherosclerosis at an early stage, measurement of flow mediated vasodilation of the brachial artery may be more helpful than measuring thickness of the vascular wall.
authors.affiliation: Department of Endocrinology, Diabetes and Vascular Medicine, University of Tübingen, Otfried-Müller Strasse 10, 72076, Tübingen, Germany. bernd.balletshofer@med.uni-tuebingen.de
authors.forename: Bernd M
authors.initials: BM
authors.lastname: Balletshofer
authors.forename: Kilian
authors.initials: K
authors.lastname: Rittig
authors.forename: Jan
authors.initials: J
authors.lastname: Stock
authors.forename: Angela
authors.initials: A
authors.lastname: Lehn-Stefan
authors.forename: Dietrich
authors.initials: D
authors.lastname: Overkamp
authors.forename: Klaus
authors.initials: K
authors.lastname: Dietz
authors.forename: Hans U
authors.initials: HU
authors.lastname: Häring
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D002340:Carotid Artery Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D017536:Carotid Artery, Common; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology* / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D011336:Probability; D018570:Risk Assessment; D012720:Severity of Illness Index; D017540:Tunica Media / Q000473:pathology*; D014664:Vasodilation