Paradoxical increase in dermal microvascular flow in pre-diabetes associated with elevated levels of CRP.

Although microvascular complications are frequent in diabetes, the pathogenesis underlying these morbidities remains unclear. Chronic inflammation appears to play a role both in the development of vascular dysfunction and diabetes. Evaluation of microvascular status in the prediabetic stages would provide a better insight into the natural progression of the disease, both from the vascular and metabolic perspective. Microvascular function was assessed in sixty rhesus monkeys using laser Doppler fluximetry. These included monkeys who had been calorie-restricted (CR); normal non-diabetic ad libitum fed (N) monkeys; Prediabetic (PreDM) monkeys with either impaired fasting glycemia, glucose intolerance or insulin resistance; and overtly diabetic monkeys (DM) with fasting glucose levels above 126 mg/dl. Body weight, per cent body fat, fasting glucose and insulin levels, glucose disposal rate during an intravenous glucose tolerance test (K(glucose)), and insulin sensitivity (M-rate) as assessed by the euglycemic, hyperinsulinemic clamp procedure were measured. Routine clinical chemistry and hematology were also performed. Our results show that in prediabetes, dermal microvascular flow is characterized by an increase in response to thermogenic provocation. We further show that this paradoxical increase is significantly and highly correlated with circulating high sensitivity CRP levels. The study demonstrates that both mild chronic inflammation and elevated skin microvascular perfusion precede overt diabetes.