Kingsley‐Berg, Shirley M.

Local warming in human skin elicits a biphasic vasodilation with a local sensory nerve component (initial peak) and nitric oxide mediated plateau. Though microvascular dysfunction in type 2 diabetes mellitus (T2DM) is well known, effects at the neural level of control in individuals with well managed T2DM are less understood. We tested the hypothesis that local sensory nerve contributions to vasodilation are less in T2DM compared to healthy controls (C). We measured skin blood flow using laser‐Doppler flowmetry (LDF) and arterial pressure using Finometer in T2DM and C subjects at baseline and during 35 minutes of local warming (LW) of the skin to 42 °C. Two LDF sites received Ringers via microdialysis throughout LW; one site was pretreated with local lidocaine (LIDO) to block local sensory innervation. Maximum cutaneous vascular conductance (CVC) was evaluated using microdialysis of nitroprusside. In preliminary studies (N = 4 T2DM, 6 C), CVC during the initial peak at the untreated site was decreased in T2DM (73 ± 4 vs. C: 85 ± 5 % max; P = 0.05), but was not different at the LIDO site (T2DM: 54 ± 9 vs. C: 66 ± 6 % max; P > 0.05). The difference between sites (sensory nerve contribution) was similar between groups (T2DM: 19 ± 7 vs. C: 18 ± 7 % max; P > 0.05), and was lower with LIDO than was previously shown with local EMLA. Our results suggest a non‐neural component which is decreased in T2DM. Supported by NIH HL73884 and CTSA UL1 RR024150.

Thermoregulatory increases in skin blood flow in humans are brought about by a combination of cutaneous vasodilation and increased cardiac output. As such, whole body heating (WBH) in humans is associated with increased heart rate and decreased blood pressure compared to normothermic baseline conditions. We hypothesized that the tachycardia and hypotension associated with WBH in resting humans would be diminished in individuals with type 2 diabetes mellitus (T2DM) compared to controls (C) of similar age due to altered autonomic control of cardiac function in T2DM. We measured heart rate (HR; ECG) and beat‐to‐beat blood pressure (Finometer) in 6 individuals with T2DM and 6 control subjects at baseline and during WBH with a water‐perfused suit. Resting HR and blood pressure were similar in C vs. T2DM (HR: C: 59 ± 2; T2DM: 62 ± 4, P > 0.05; MAP: C: 93 ± 7; T2DM: 95 ± 7, P > 0.05). During body heating, heart rate increased significantly in both groups; at peak of WBH, HR was 91 ± 4 in C and 92 ± 1 in T2DM. This represented a change of 32 ± 3 in C and 27 ± 3 in T2DM (P > 0.05). Our preliminary data suggest a similar increase in HR and decrease in BP during body heating in T2DM when compared with C. This may have implications for clinical applications in the treatment and management of T2DM, particularly with regard to heat exposure and/or exercise.

Cutaneous sensory nerve-mediated vasodilation is an important component of normal microvascular responsiveness to thermal and nonthermal stimuli. Since both neural and microvascular function can be impaired in type 2 diabetes mellitus (T2DM), we tested the hypothesis that local sensory nerve-mediated vasodilation during nonpainful local warming of the skin is less in T2DM compared with healthy controls (C) matched for age and body size. The rapid vasodilation during the first ∼5 min of this local warming (“initial peak”) was previously shown to rely primarily on local sensory nerves. We measured skin blood flow in T2DM and C subjects ( n = 7 in each group) at baseline and during 35 min of local warming of the skin to 42°C at two sites on the ventral forearm. One site was pretreated with 4% lidocaine (LIDO) to block local sensory innervation. During local warming, cutaneous vascular conductance (CVC) during the initial peak was not different between groups, either at the untreated site [T2DM 75 ± 2 vs. C 81 ± 6% of maximum CVC (%maxCVC); P > 0.05] or at the LIDO site (T2DM 63 ± 7 vs. C 64 ± 6%maxCVC; P > 0.05). The difference between untreated and LIDO sites (sensory nerve contribution) was also similar between groups (T2DM 13 ± 5 vs. C 18 ± 5%maxCVC; P > 0.05) and was smaller with LIDO than was previously shown with other local anesthetics. Our results suggest that relatively healthy individuals with T2DM do not exhibit impairments in local sensory nerve vasodilation during thermal stimulation compared with controls of similar age and body size.