title: Basal and exercise-induced skeletal muscle blood flow is augmented in type I diabetes mellitus.
abstract: Hyperaemia occurs early in the renal and retinal microcirculation of patients with type I (insulin-dependent) diabetes mellitus, and may be critical in the development of nephropathy and retinopathy. We therefore sought to determine whether resting and exercise-induced hyperaemia was also apparent in the skeletal muscle circulation of young subjects with type I diabetes. Blood flow was assessed by venous occlusion plethysmography in 18 diabetic (DM) subjects and 20 matched controls. Exercise entailed 2 min of isotonic exercise against no load. Endothelium-dependent and -independent vasodilator function was assessed following intra-arterial infusion of acetylcholine and sodium nitroprusside respectively. Forearm blood flow (FBF) was higher in DM subjects than in controls (3.3+/-0.3 and 2.2+/-0.2 ml x min(-1) x 100 ml(-1) forearm respectively; P<0.005). This was not due to differences in forearm or body size, blood pressure, heart rate, lipid status or glycaemic control. Peripheral insulin levels were higher in DM subjects than in controls (48.5+/-8 and 15.5+/-1.5 micro-units/ml respectively; P<0.005). Resting FBF was closely correlated with insulin levels (r(2)=0.4; P<0.005). Parameters of exercise-induced hyperaemia [including peak flow (16.4+/-1.4 and 12.0+/-0.7 ml x min(-1) x 100 ml(-1) forearm in DM and control subjects respectively; P<0.01) and the volume repaid to the forearm at 5 min post-exercise (32.1+/-3.1 and 23.1+/-1.4 ml x 100 ml(-1) forearm respectively; P<0.05)] were also significantly greater in DM subjects, even when differences in resting FBF were taken into account. Peak hyperaemic blood flow and the volume repaid at 5 min were also related to insulin levels (r(2)=0.16; P<0.05 and r(2)=0.27; P<0.005 respectively). The vasodilator response to acetylcholine was reduced in DM subjects (P<0.05; analysis of variance), and the slope of this dose-flow relationship was inversely related to insulin levels (r(2)=0.2; P<0.05). These data show that both resting and exercise-induced skeletal muscle blood flow are augmented in young patients with type I diabetes, possibly due to the vasodilatory effect of increased insulin levels. Diminished vasodilator responses to acetylcholine may also, in part, be a consequence of insulin-augmented resting muscle blood flow.
authors.affiliation: Centre for Heart and Chest Research, Monash Medical Centre and Monash University, 246 Clayton Road, Clayton, Melbourne, Victoria 3168, Australia.
authors.forename: R A
authors.initials: RA
authors.lastname: Skyrme-Jones
authors.forename: K L
authors.initials: KL
authors.lastname: Berry
authors.forename: R C
authors.initials: RC
authors.lastname: O'Brien
authors.forename: I T
authors.initials: IT
authors.lastname: Meredith
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D015444:Exercise / Q000502:physiology*; D005260:Female; D005542:Forearm; D006801:Humans; D007328:Insulin / Q000097:blood; D016014:Linear Models; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009599:Nitroprusside / Q000494:pharmacology; D010991:Plethysmography; D012039:Regional Blood Flow; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D007328:Insulin; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine