Skin blood flow and nitric oxide during body heating in type 2 diabetes mellitus

Abstract

Individuals with type 2 diabetes mellitus (T2DM) often exhibit microvascular dysfunction that may contribute to impaired thermoregulation, but potential mechanisms remain unclear. Our goals were to quantify skin blood flow responses and nitric oxide-mediated vasodilation during body heating in individuals with T2DM compared with nondiabetic control subjects of similar age. We measured skin blood flow (laser-Doppler flowmetry) in conjunction with intradermal microdialysis of N(G)-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase inhibitor) or vehicle during 45-60 min of whole body heating (WBH) in 10 individuals with T2DM and 14 control subjects. In six individuals from each group, we also measured forearm blood flow (FBF) by venous occlusion plethysmography on the contralateral forearm. FBF responses showed diminished absolute cutaneous vasodilation during WBH in the T2DM group (P(ANOVA) < 0.01; peak FBF in control 13.1 +/- 1.7 vs. T2DM 9.0 +/- 1.6 ml.100 ml(-1).min(-1)). However, the relative contribution of nitric oxide to the cutaneous vasodilator response (expressed as % of maximal cutaneous vascular conductance) was not different between groups (P > 0.05). We conclude that cutaneous vasodilator responses to WBH are decreased in individuals with T2DM, but the contribution of nitric oxide to this smaller vasodilation is similar between T2DM and control individuals. This decrease in cutaneous vasodilation is likely an important contributor to impaired thermoregulation in T2DM.

Local sensory nerve control of skin blood flow during local warming in type 2 diabetes mellitus

“…We previously reported that cutaneous vasodilation during whole body heating exhibited a delayed onset in T2DM subjects (14) and that overall vasodilator responses were lower at a given core temperature in T2DM compared with control subjects of similar age and body size (13). Additionally, we found that the prolonged local warming response (nitric oxidedependent "plateau phase" vasodilation) was decreased in T2DM subjects (12,14).…”

“…Blood glucose was measured in all T2DM subjects before any procedures began. Two intradermal microdialysis fibers (MD-2000; Bioanalytical Systems) were placed in the skin on the ventral surface of the left forearm of each subject, as previously described (12,13). Ice was placed on the skin surface for 2-3 min to numb the area.…”

“…Subjects were asked whether they felt any pain or discomfort during the local warming; no subject reported feeling any pain or discomfort. SNP (28 mM) was then infused at both LIDO and untreated sites for ϳ40 min to elicit maximum CVC (12,13). Ambient temperature in the study room was held at 22-24°C during all experiments.…”

“…As the incidence and prevalence of T2DM are increasing, also increasing are the number of individuals who are otherwise relatively healthy and live with T2DM but manage it well so that the number of comorbid conditions is minimal. We have therefore focused our efforts on this growing population in our attempts to understand mechanisms of cutaneous microvascular dysfunction in T2DM (12)(13)(14). Recent studies in our laboratory have shown that relatively healthy individuals with T2DM exhibit less nitric oxide-dependent vasodilation during local and whole body thermal stimuli compared with age-matched controls (12,13).…”

“…We have therefore focused our efforts on this growing population in our attempts to understand mechanisms of cutaneous microvascular dysfunction in T2DM (12)(13)(14). Recent studies in our laboratory have shown that relatively healthy individuals with T2DM exhibit less nitric oxide-dependent vasodilation during local and whole body thermal stimuli compared with age-matched controls (12,13). Peripheral neuropathy is likely linked to microvascular dysfunction in T2DM, but specific mechanisms of diminished sensory nerve-mediated vasodilation during local warming of the skin are, as yet, undefined.…”