Effects of Adding Exercise to a 16-Week Very Low-Calorie Diet in Obese, Insulin-Dependent Type 2 Diabetes Mellitus Patients

Context: Reduction of 50% excess body weight, using a very low-calorie diet (VLCD; 450 kcal/d) improves insulin sensitivity in obese type 2 diabetes mellitus patients. Objective: The objective of the study was to evaluate whether adding exercise to the VLCD has additional benefits. Design: This was a randomized intervention study. Setting: The study was conducted at a clinical research center in an academic medical center. Subjects: Twenty-seven obese [body mass index 37.2 +/- 0.9 kg/m(2) (mean +/- SEM)] insulin-treated type 2 diabetes mellitus patients. Intervention: Patients followed a 16-wk VLCD. Thirteen of them simultaneously participated in an exercise program (E) consisting of 1-h, in-hospital training and four 30-min training sessions on a cycloergometer weekly. Outcome Measures: Insulin resistance was measured by a hyperinsulinemic euglycemic clamp. Insulin signaling, mitochondrial DNA (mtDNA) content, and intramyocellular lipid content was measured in skeletal muscle biopsies. Results: Baseline characteristics were identical in both groups. Substantial weight loss occurred (-23.7 +/- 1.7 kg VLCD-only vs. -27.2 +/- 1.9 kg VLCD+E, P = NS within groups). The exercise group lost more fat mass. Insulin-stimulated glucose disposal increased similarly in both study groups [15.0 +/- 0.9 to 39.2 +/- 4.7 mu mol/min(-1) . kg lean body mass (LBM-1) VLCD-only vs. 17.0 +/- 1.0 to 37.5 +/- 3.5 mu mol/min(-1) . kg LBM-1 in VLCD+E], as did phosphorylation of the phosphatidylinositol 3-kinase-protein kinase B/AKT insulin signaling pathway. In contrast, skeletal muscle mtDNA content increased only in the VLCD+E group (1211 +/- 185 to 2288 +/- 358, arbitrary units, P = 0.016 vs. 1397 +/- 240 to 1196 +/- 179, P = NS, VLCD-only group). Maximum aerobic capacity also only increased significantly in the VLCD+E group (+6.6 +/- 1.7 ml/min(-1) . kg LBM-1 vs. +0.7 +/- 1.5 ml/min(-1) . kg LBM-1 VLCD-only, P = 0.017). Conclusion: Addition of exercise to a 16-wk VLCD induces more fat loss. Exercise augments maximum aerobic capacity and skeletal muscle mtDNA content. These changes are, however, not reflected in a higher insulin-stimulated glucose disposal rate. (J Clin Endocrinol Metab 97: 2512-2520, 2012)