Fasting plasma glucose is a composite measure of hepatic glucose production (HGP) and non-insulin-dependent (basal) tissue glucose clearance rate (bGCR). A rise in fasting plasma glucose, within the nondiabetic range, is purported to be regulated by decreased bGCR rather than increased HGP. However, the role of bGCR in improving metabolic syndrome (MetS) is not yet fully understood. We sought to explore the novel impact of weight loss induced by exercise on bGCR in individuals with MetS. Fourteen sedentary adults with MetS (9 females, 68 years, 35.2 kg/m2) participated in a 12-week moderate intensity exercise program (~65% VO2max, 1 hr/day, 5 days/week). MetS was defined using ATP III guidelines. Insulin resistance (IR) was estimated using a hyperinsulinemic (40 mU/m2/min) euglycemic (90 mg/dL) clamp. Rate of glucose disappearance (Rd) was determined using [6,6-2H2]-glucose during fasting and insulin stimulation. GCR was calculated as Rd relative to the prevailing glucose concentration. At baseline, bGCR correlated with IR and adiponectin (r=0.69 and 0.68, P<0.01). Following exercise training and relative to pre-intervention: (i) body weight, VO2max and IR improved (6.6, 17 and 7.7%, respectively; P<0.05); (ii) cardiometabolic risk factors decreased (Triglycerides: 30%; Total Cholesterol: 15%; LDL: 15%; sBP: 11% and dBP: 14.5%; all P<0.05); (iii) fasting glucose and insulin concentration decreased (6% and 32%, P<0.05), and bGCR increased (~1.5 fold, P<0.01). The increase in bGCR correlated positively with changes in body weight, fat mass, suppression of HGP during the clamp, and serum triglycerides (r=0.5, 0.49, 0.61 and 0.62, respectively; P<0.05). Weight loss following aerobic exercise training breaks the vicious cycle of increased insulin resistance and secretion by increasing the contribution of bGCR to fasting glycemia. This evidences the unique and multifactorial benefits of exercise concomitant with weight loss in mediating cardiometabolic risk.
A. Hari: None. C.L. Axelrod: None. J.T. Mey: None. J.P. Kirwan: None.
National Institutes of Health; National Center for Research Resources