Lack of Association Between the Pro12Ala Polymorphism in PPAR-gamma2 Gene and Body Weight Changes, Insulin Resistance and Chronic Diabetic Complications in Obese Patients with Type 2 Diabetes

Background: It is generally accepted that the Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with an increased risk of type 2 diabetes. However, studies on an association between the polymorphism and obesity have yielded inconsistent findings. Also, a role of PPAR-gamma receptors in development of chronic diabetic complications cannot be excluded. The aim of this study was to investigate an association between Pro12Ala polymorphism and body weight changes, insulin resistance, insulin secretion and incidence of diabetic complications in obese patients with long-lasting type 2 diabetes.

Methods: In 216 obese patients with at least a 10-year history of type 2 diabetes, a detailed medical history was taken and a physical examination with assessment of diabetic complications was performed as well as evaluation of insulin resistance (homeostatic model assessment-HOMA), insulin secretion and other biochemical parameters. PCR-RFLP was used to assess Pro12Ala polymorphism. Two subgroups of patients were compared: homozygotic Pro/Pro and Ala allele carriers (Ala/Ala + Ala/Pro).

Results: No differences between the analyzed groups in body weight changes, insulin resistance and insulin secretion were found, but Ala allele was significantly more frequent in males than in females. There was no difference in incidence and progression of diabetic complications with only a trend towards higher incidence of diabetic retinopathy in patients with Ala allele.

Conclusions: There is no association between Pro12Ala PPAR-gamma2 polymorphism and body mass changes observed during a course of type 2 diabetes, differences in peripheral insulin resistance and incidence and progression of diabetic complications in obese patients with long-lasting type 2 diabetes.