Reduced Skeletal Muscle Oxygen Uptake and Reduced β-Cell Function

Reduced Skeletal Muscle Oxygen Uptake and Reduced β-Cell Function Two early abnormalities in normal glucose-tolerant offspring of patients with type 2 diabetes Claus Thamer , MD 1 , Michael Stumvoll , MD 1 , Andreas Niess , MD 2 , Otto Tschritter , MD 1 , Michael Haap , MD 1 , Regine Becker , MD 1 , Fatemeh Shirkavand , MD 1 , Oliver Bachmann , MD 1 , Kristian Rett , MD 3 , Annette Volk , MD 1 , Hans Häring , MD 1 and Andreas Fritsche , MD 1 1 Department of Endocrinology and Metabolism, Eberhard-Karls-University, Tübingen, Germany 2 Center of Internal Medicine, Department of Rehabilitative & Preventive Sports Medicine, University of Freiburg, Freiburg, Germany 3 Deutsche Klinik für Diagnostik, Wiesbaden, Germany Address correspondence and reprint requests to PD Dr. med. Andreas Fritsche, Medizinische Universitätsklinik, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany. E-mail: andreas.fritsche{at}med.uni-tuebingen.de . Abstract OBJECTIVE —Studies on insulin sensitivity and insulin secretion in subjects with a familial predisposition for type 2 diabetes mellitus (T2DM) traditionally produce inconsistent results. This may be due to small sample size, subject selection, matching procedures, and perhaps lack of a measure of physical fitness. RESEARCH DESIGN AND METHODS —In the present study, we specifically tested the hypothesis that a family history of T2DM is associated with reduced V o 2max , measured by incremental bicycle ergometry, independent of insulin sensitivity estimated from an oral glucose tolerance test (OGTT; n = 424) and measured by a euglycemic-hyperinsulinemic clamp ( n = 185). Subjects included in the study were young (34 ± 10 years), healthy, and normal glucose tolerant with either a first-degree relative (FDR) with T2DM ( n = 183), a second-degree relative with T2DM ( n = 94), or no family history of T2DM (control subjects, n = 147). BMI, percent body fat, waist-to-hip ratio (WHR), and habitual physical activity (HPA; standard questionnaire) were comparable among groups. FDRs had significantly lower V o 2max than control subjects: 40.5 ± 0.6 vs. 45.2 ± 0.9 ml O 2 /kg lean body mass, P = 0.01 after adjusting for sex, age, BMI, HPA, and insulin sensitivity (euglycemic-hyperinsulinemic clamp). RESULTS —BMI, percent body fat, waist-to-hip ratio (WHR), and habitual physical activity (HPA; standard questionnaire) were comparable among groups. FDRs had significantly lower V o 2max than control subjects: 40.5 ± 0.6 vs. 45.2 ± 0.9 ml O 2 /kg lean