title: Specific impairment of endothelium-dependent vasodilation in subjects with type 2 diabetes independent of obesity.
abstract: In subjects with type 2 diabetes in whom an impaired response to an endothelial-dependent vasodilator has been characterized, the populations have also been at least moderately obese. Obesity has been characterized as an independent predictor of endothelial dysfunction in nondiabetic subjects. We hypothesized that in normotensive subjects with type 2 diabetes compared with age-matched control subjects, 1) endothelium-dependent vasodilation, as demonstrated by the forearm blood flow (FABF) response to intraarterial acetylcholine, would be decreased; 2) endothelium-independent vasodilation, as demonstrated by the FABF response to intraarterial nitroprusside, would be similar; 3) the degree of insulin resistance, as measured by the insulin sensitivity index (SI), would predict greater impairment in the FABF response to acetylcholine; and 4) these relationships would be independent of obesity. We measured FABF by venous occlusion plethysmography during brachial arterial infusions of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator nitroprusside in 20 control and 17 subjects with type 2 diabetes. We measured SI using the frequently sampled i.v. glucose tolerance test. Among the diabetic relative to the control subjects we identified a decrease in the acetylcholine-mediated percent increase in FABF (P = 0.02). Using the absolute FABF response to acetylcholine and including adjustments for body mass index and other covariates, the overall group difference remained and was noted to be greatest in those subjects who had lower baseline FABFs. In contrast, no significant difference in the nitroprusside-mediated increase in the percent change FABF was identified between groups (P = 0.30). Finally, the degree of insulin resistance, as measured by SI, did not independently predict greater impairment of the FABF response to acetylcholine. This study is the first to identify specific endothelial cell dysfunction that remains significant after adjustment for obesity in a population of normotensive subjects with type 2 diabetes.
authors.affiliation: Department of Internal Medicine, University of Michigan, USA. hogikyan@umich.edu
authors.forename: R V
authors.initials: RV
authors.lastname: Hogikyan
authors.forename: A T
authors.initials: AT
authors.lastname: Galecki
authors.forename: B
authors.initials: B
authors.lastname: Pitt
authors.forename: J B
authors.initials: JB
authors.lastname: Halter
authors.forename: D A
authors.initials: DA
authors.lastname: Greene
authors.forename: M A
authors.initials: MA
authors.lastname: Supiano
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D001783:Blood Flow Velocity; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage; D014664:Vasodilation; D014665:Vasodilator Agents
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine