Influence of Pro12Ala peroxisome proliferator-activated receptor γ2 polymorphism on glucose response to exercise training in type 2 diabetes

Aims/ hypothesis: Exercise training improves glycaemic control in some but not all individuals and little research has been done regarding genetic impact on the exercise training response in type 2 diabetes. The purpose of this study was to investigate the influence of the Pro(12)Ala variant of the peroxisome proliferator-activated receptor (PPAR) gamma 2 gene on changes in fasting plasma glucose in response to exercise training. Methods: The study population comprised 139 sedentary type 2 diabetic patients (age: 54.4 +/- 7.2; HbA(1)c: 7.7 +/- 0.9%) who completed 3 months of supervised exercise training. The primary outcome variable in our analysis was the post-intervention change in blood glucose. Other assessments included measures of body composition, insulin sensitivity indices and maximal oxygen uptake (VO(2)max). Results: The frequency of the Ala allele was 8.3% and the genotypes were in Hardy-Weinberg equilibrium. At baseline, neither body composition variables ( weight, BMI, waist circumference), glucose homeostasis variables ( glucose, insulin, HbA(1)c, homeostasis model assessment method) nor VO2max were different between genotypes ( wild- type: Pro(12)Pro n= 117, Ala carriers: X(12)Ala n= 22). The exercise-training intervention led to similar improvements in body composition and glucose homeostasis variables in both genotype groups ( p < 0.05). The change in fasting plasma glucose was significantly different between PPAR.2 genotypes (-1.66 mmol/lvs - 0.54 mmol/l, Ala carriers and wild- type, respectively) ( p= 0.034 unadjusted and p= 0.089 including baseline glucose) and the significant association between genotype and glucose response remained after adjusting for statistically significant predictors ( age, changes in insulin and BMI [ p= 0.015]) and including baseline glucose, insulin and BMI ( p= 0.031). Conclusions/ interpretation: These data suggest that the Pro(12)Ala polymorphism may influence the glycaemic response to exercise in type 2 diabetes.