Skin microvascular reactivity correlates to clinical microangiopathy in type 1 diabetes: A pilot study

Abstract

Aim: The aim of this study was to investigate the correlation between skin microvascular reactivity and clinical microangiopathy in patients with type 1 diabetes.

Methods: We included 61 patients with type 1 diabetes, that is, 31 patients with and 30 without clinical microangiopathy, and 31 healthy controls. A microangiopathy scoring system was introduced for comparison of data between patients with microangiopathy. Responses to iontophoresis of acetylcholine and sodium nitroprusside were assessed by laser Doppler imaging.

Results: Patients with microangiopathy had reduced acetylcholine- and sodium nitroprusside-mediated flux in forearm skin microcirculation compared to healthy controls (p = 0.03 and p < 0.001, respectively, repeated measures analysis of variance), whereas no significant differences were found between patients without microangiopathy and controls. Skin reactivity was reduced in patients with microangiopathy compared to patients without microangiopathy: 1.43 ± 0.38 versus 1.59 ± 0.39 arbitrary units for acetylcholine-mediated peak flux and 1.44 ± 0.46 versus 1.74 ± 0.34 arbitrary units for sodium nitroprusside-mediated peak flux (p < 0.05 for both). A tendency of gradual decrease in acetylcholine and sodium nitroprusside responses was found in patients with increasing microangiopathy scores.

Conclusion: We conclude that skin microvascular reactivity is associated with clinical microangiopathy in patients with type 1 diabetes. Impaired skin microvascular function in type 1 diabetes seems to be multifactorial and involves both endothelial-dependent and endothelial-independent pathways. We introduce a novel microangiopathy score that could easily be used in a clinical setting for comparison of patients with various degrees of microangiopathy.

Keywords: Type 1 diabetes; clinical microangiopathy; iontophoresis; skin microvascular function.

Figure 1.

Increases in skin microvascular flux in response to acetylcholine and sodium nitroprusside iontophoresis in patients with type 1 diabetes and healthy controls. Data show mean values and 95% CI of skin perfusion in arbitrary units (AU) before and after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Figure 1(a) and (c) shows results of patients with no microvascular complications (white circles), patients with microvascular complications (black circles) and healthy controls (red circles). Patients with microangiopathy had, compared to controls, reduced microvascular responses to ACh (p = 0.03, repeated measures ANOVA) and SNP (p < 0.001). Patients with microangiopathy also had reduced SNP-mediated responses compared to patients without complications (p = 0.01), while ACh-mediated responses were not significantly different. Subgroup analyses of patients with various microangiopathy scores (Figure 1(b) and (d)) show a gradual decrease in both ACh- and SNP-mediated responses in patients with increasing microangiopathy scores.