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

• Published in: The journal of clinical endocrinology and metabolism 2012-07, Vol.97 (7), p.2512-2520
• Main Authors: Snel, Marieke, Gastaldelli, Amalia, Ouwens, D. Margriet, Hesselink, Matthijs K. C, Schaart, Gert, Buzzigoli, Emma, Frölich, Marijke, Romijn, Johannes A, Pijl, Hanno, Meinders, A. Edo, Jazet, Ingrid M
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Caloric Restriction; Calorimetry, Indirect; Combined Modality Therapy; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diet therapy; Diabetes Mellitus, Type 2 - therapy; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exercise - physiology; Exercise Therapy; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hypoglycemic Agents - therapeutic use; Insulin - therapeutic use; Male; Medical sciences; Middle Aged; Obesity - complications; Obesity - diet therapy; Obesity - therapy; Time Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2011-3178

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/m2 (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 μmol/min−1 · kg lean body mass (LBM−1) VLCD-only vs. 17.0 ± 1.0 to 37.5 ± 3.5 μmol/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.