Influence of Pro12Ala peroxisome proliferator-activated receptor gamma2 polymorphism on glucose response to exercise training in type 2 diabetes

Diabetologia. 2005 Aug;48(8):1503-9. doi: 10.1007/s00125-005-1827-y. Epub 2005 Jun 29.


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) gamma2 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(2max)).

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 VO(2max) 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 PPARgamma2 genotypes (-1.66 mmol/l vs -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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anaerobic Threshold
  • Blood Glucose / metabolism*
  • Body Composition / physiology
  • Diabetes Mellitus, Type 2 / blood*
  • Exercise / physiology*
  • Female
  • Genotype
  • Homeostasis / physiology
  • Humans
  • Male
  • Middle Aged
  • PPAR gamma / genetics*
  • Physical Fitness / physiology*
  • Polymorphism, Genetic / genetics*
  • Prospective Studies


  • Blood Glucose
  • PPAR gamma