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

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/m 2 ); 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 VO 2 max (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.