An increased skin microvessel density is associated with neurovascular complications in type 1 diabetes mellitus

The aim of this study was to assess the blood vessel density and maturity in the skin of adults with type 1 diabetes in relation to the presence of late neurovascular complications. We included 148 patients (87 men) with a median (interquartile range) age of 41 (31-49) and median diabetes duration of 21 (17-30) years. Microvessel (CD133, CD34, CD31 and von Willebrand factor) markers were evaluated by indirect immunohistochemistry assay in material from a skin biopsy. Diabetic retinopathy was diagnosed using direct ophthalmoscopy, and diabetic kidney disease was estimated in people with increased albuminuria and a 10-year duration of diabetes or evidence of diabetic retinopathy . Diabetic peripheral neuropathy diagnosis was based on Toronto definition, cardiac autonomic neuropathy on validated ProSciCard III program. Microvessel density, assessed by CD34 and CD133, was significantly higher in patients with cardiac autonomic neuropathy [160 (125-175) vs 121 (100-154)/1 mm², p = 0.001 and 92 (83-104) vs 79 (63-92)/1 mm², p = 0.007, respectively] and CD34 in patients with diabetic peripheral neuropathy [135 (106-168) vs 121 (95-145)/1 mm², p = 0.018], as compared with subjects without complications. In multivariate logistic regression, density of CD34 and CD133 positive vessels was associated with presence of cardiac autonomic neuropathy [odds ratio 1.016 (95% confidence interval: 1.002-1.029), p = 0.019 and odds ratio 1.037 (95% confidence interval: 1.008-1.067), p = 0.011, respectively]. It was independent from age, sex, diabetes duration, smoking status, body mass index and HbA1c value. Density of CD34 positive vessels was also associated with diabetic peripheral neuropathy, independently from sex and diabetes duration [odds ratio 1.009 (95% confidence interval: 1.001-1.020), p = 0.037]. Skin microvessel density is increased in adults with clinical evidence of neurovascular complications of type 1 diabetes. This is associated with predominance of the vessels of low maturity.