Association of the Pro12Ala Polymorphism in the PPAR-2 Gene With 3-Year Incidence of Type 2 Diabetes and Body Weight Change in the Finnish Diabetes Prevention Study

The association of the Pro12Ala polymorphism of the PPAR-2 gene with the incidence of type 2 diabetes was investigated in 522 subjects with impaired glucose tol-erance (IGT) participating in the Finnish Diabetes Pre-vention Study. Subjects were randomized to either an intensive diet and exercise group or a control group. By 3 years of intervention, the odds ratio of the develop-ment of type 2 diabetes for subjects with the Ala12 allele was 2.11-fold compared with that for subjects with the Pro12Pro genotype (95 % CI 1.20–3.72). The risk for type 2 diabetes increased also in subjects who gained weight or belonged to the control group. In the intervention group, subjects with the Ala12Ala geno-type lost more weight during the follow-up than sub-jects with other genotypes (Pro12Pro vs. Ala12Ala P 0.043), and none of subjects with the Ala12Ala genotype developed type 2 diabetes in this group. In conclusion, the Ala12 allele may predispose to the development of type 2 diabetes in obese subjects with IGT. However, beneficial changes in diet, increases in physical activity, and weight loss may reverse, to some extent, the diabe-togenic impact of the Ala12 allele, possibly due to an improved insulin sensitivity. Diabetes 51:2581–2586, 2002 Type 2 diabetes is preceded by impaired glucosetolerance (IGT) that can last for years before thediagnosis of diabetes. Two earlier interventionstudies suggest that it is possible to reduce the incidence of type 2 diabetes among subjects with IGT by lifestyle intervention (1,2). Recently, we demonstrated that in subjects with IGT weight loss, increased physical activity and healthier diet in terms of reduced fat and increased dietary fiber intake resulted in a substantial reduction in the incidence of type 2 diabetes (3). Similarly, the efficacy of lifestyle intervention in prevention of type 2 diabetes has been confirmed in multiethnic populations i