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Horm Metab Res 2005; 37(2): 99-105
DOI: 10.1055/s-2005-861174
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

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
Further Information

Publication History

Received 6 May 2004

Accepted after revision 11 August 2004

Publication Date:
21 March 2005 (online)

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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

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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

Phone: +45 8949 2071

Fax: +45 8949 2072 ·

Email: oest@dadlnet. dk