Influence of the PPAR-γ2 Pro12Ala and ACE I/D Polymorphisms on Insulin Sensitivity and Training Effects in Healthy Offspring of Type 2 Diabetic Subjects

T. Østergård; J. Ek; Y. Hamid; B. Saltin; O. B. Pedersen; T. Hansen; O. Schmitz

doi:10.1055/s-2005-861174

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2005; 37(2): 99-105
DOI: 10.1055/s-2005-861174

Original Clinical

Influence of the PPAR-γ2 Pro12Ala and ACE I/D Polymorphisms on Insulin Sensitivity and Training Effects in Healthy Offspring of Type 2 Diabetic Subjects

T. Østergård ¹ , J. Ek ² , Y. Hamid ² , B. Saltin ³ , O. B. Pedersen ² , T. Hansen ² , O. Schmitz ¹

¹Department of Endocrinology and Diabetes M, Aarhus University Hospital, Aarhus Sygehus, and Department of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark
²Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
³Copenhagen Muscle Research Center, Rigshospitalet, Copenhagen, Denmark

Abstract

Aerobic endurance training improves insulin sensitivity, and is of great importance in the prevention and treatment of type 2 diabetes. The improvement in insulin sensitivity and cardiovascular function through exercise is highly variable among individuals, and is probably partly determined by genetic components. This study evaluated the peroxisome proliferation-activated receptor-γ2 (PPAR-γ2) Pro12Ala polymorphism and the angiotensin converting enzyme (ACE) I/D polymorphism with respect to any potential influence that these highly prevalent polymorphisms may impose on changes in insulin sensitivity and maximal aerobic capacity induced by exercise. Seventy-nine healthy first-degree relatives of type 2 diabetic patients were compared to a control group consisting of 54 subjects without any family history of type 2 diabetes. All subjects had a normal OGTT. The groups were comparable with respect to age (34 ± 7 vs. 33 ± 7 years), gender ((m/f) 43/36 vs. 30/24) and BMI (25.7 ± 2.6 vs. 25.3 ± 2.5 kg/m²); p (all) = NS. Furthermore, a subgroup of 29 offspring and 17 control subjects were engaged in a standardized training program lasting ten weeks. Insulin sensitivity (hyperinsulinemic euglycemic clamp technique) and VO₂max (exhaustive exercise test) was assessed before and after the training period. We will demonstrate the allelic frequency of the Ala-allele of the Pro12Ala polymorphism to be lower in offspring to type 2 diabetic patients (13.3 %) compared to control subjects (21.3 %); p < 0.05. In offspring only, the Pro12Ala polymorphism of the PPAR-γ2 gene appeared to enhance weight changes brought about by exercise (Δweight = - 0.3 ± 1.4 kg vs. - 1.8 ± 1.8 kg; p < 0.05; (Pro/Pro vs. Pro/Ala + Ala/Ala) - suggesting possible gene-environment or gene-gene interactions. The ACE I/D polymorphism was not of significant importance in determining the capability of responding to exercise in terms of improvement in insulin sensitivity or maximal aerobic capacity.

Key words

Polymorphism · Type 2 diabetes · Exercise · Insulin resistance

Full Text

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T. Østergård, M. D.

Department of Medicine M (Endocrinology & Diabetes) Aarhus University Hospital, Aarhus Sygehus

Nørrebrogade 42-44 · DK-8000 Aarhus C · Denmark

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