Effects of Exercise on sRAGE Levels and Cardiometabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized Controlled Trial

CONTEXT: Low levels of soluble receptor for advanced glycation end-products (sRAGE) have been linked to systemic inflammation and vascular complications in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: We examined the effects of exercise on sRAGE and its association with diverse cardiometabolic risk factors and indicators of atherosclerosis in patients with T2DM. DESIGN, SETTING, AND PARTICIPANTS: Seventy-five patients with T2DM were randomized into a control group and an aerobic exercise group (60 min at moderate intensity, five times/wk for 12 wk). MAIN OUTCOME MEASURES: We evaluated sRAGE, energy expenditure, dietary energy intake, cardiorespiratory fitness, inflammatory markers, visceral fat area, pulse-wave velocity, and flow-mediated dilatation. RESULTS: Baseline sRAGE concentrations were independently associated with age, glycated hemoglobin, glucose, triglyceride, and high-density lipoprotein cholesterol levels (R2=0.244). After 12 wk of exercise training, the exercise group showed significantly decreased body weight, waist circumference, blood pressure, glycated hemoglobin, apolipoprotein B, and free fatty acid levels. Concurrently, cardiorespiratory fitness assessed by oxygen uptake at anaerobic threshold was improved, and body fat percentage and visceral fat area were significantly decreased in the exercise group, although pulse-wave velocity and flow-mediated dilatation were not changed. Furthermore, sRAGE levels were increased and high-sensitivity C-reactive protein levels were decreased in the exercise group but not in the control group. Percent change of sRAGE level was negatively correlated with that of high-sensitivity C-reactive protein during the study period (r=-0.27; P=0.019). CONCLUSIONS: Aerobic exercise increases sRAGE levels along with improvement of various cardiometabolic risk factors in patients with T2DM.