Metformin improves skin capillary reactivity in normoglycaemic subjects with the metabolic syndrome

Abstract

AIMS. Insulin resistance and a parental history of diabetes mellitus are independently associated with endothelial dysfunction. Oxidative stress has a pivotal role in the pathophysiology of vascular injury. Metformin, in addition to its glucose-lowering properties, has vasculoprotective effects. We investigated whether metformin has beneficial effects on the nutritive skin capillary circulation and deceases oxidative stress in a group at high risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease.
METHODS. Thirty normoglycaemic subjects with the metabolic syndrome (MS), who had first-degree relatives with T2DM, participated. The mean age was 39.1 ± 8.4 years and body mass index (BMI) 35.7 ± ± 4.8 kg/m² (mean ± SD). Subjects were randomized 1:1 to receive placebo (n = 14) or metformin (n = 16; 1700 mg/day) in a double-blind study. At baseline and post treatment, blood and urine samples were collected for biochemical and 8-epi-prostaglandin F_2α (8-epi-PGF_2α) analysis, respectively. Microcirculation was assessed by nailfold videocapillaroscopy, analysing afferent (AF), efferent (EF) and apical (AP) diameters of capillary loops, functional capillary density (FCD), red blood cell velocity at rest (RBCV), after 1 min arterial occlusion (RBCV_max) and time (TRBCV_max) taken to reach it.
RESULTS. Groups did not differ significantly in anthropometric, clinical, laboratory or microvascular measurements at baseline. In the metformin group, weight, BMI, systolic blood pressure and fasting plasma glucose fell, and lipid profile and microcirculatory parameters FCD, AF, EF, AP, RBCVmax and TRBCVmax improved (all p < 0.01). No relationship between clinico-laboratory parameters and microvascular reactivity was observed, except for changes in total and lowdensity lipoprotein-cholesterol and RBCV_max. 8-epi-PGF_2α did not change significantly in either group.
CONCLUSIONS. Metformin improved skin capillary reactivity in normoglycaemic MS subjects independently of significant changes in 8-epi-PGF_2α levels.