Lindi Virpi I, Uusitupa Matti I J, Lindström Jaana, Louheranta Anne, Eriksson Johan G, Valle Timo T, Hämäläinen Helena, Ilanne-Parikka Pirjo, Keinänen-Kiukaanniemi Sirkka, Laakso Markku, Tuomilehto Jaakko
Department of Clinical Nutrition, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.
Diabetes. 2002 Aug;51(8):2581-6. doi: 10.2337/diabetes.51.8.2581.
The association of the Pro12Ala polymorphism of the PPAR-gamma2 gene with the incidence of type 2 diabetes was investigated in 522 subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention 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 development 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 genotype lost more weight during the follow-up than subjects 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 diabetogenic impact of the Ala12 allele, possibly due to an improved insulin sensitivity.
在参与芬兰糖尿病预防研究的522名糖耐量受损（IGT）受试者中，研究了PPAR-γ2基因Pro12Ala多态性与2型糖尿病发病率的关联。受试者被随机分为强化饮食和运动组或对照组。经过3年的干预，携带Ala12等位基因的受试者发生2型糖尿病的比值比是携带Pro12Pro基因型受试者的2.11倍（95%可信区间1.20 - 3.72）。体重增加或属于对照组的受试者患2型糖尿病的风险也增加。在干预组中，携带Ala12Ala基因型的受试者在随访期间比其他基因型（Pro12Pro与Ala12Ala相比，P = 0.043）的受试者体重减轻更多，且该组中携带Ala12Ala基因型的受试者均未发生2型糖尿病。总之，Ala12等位基因可能使IGT肥胖受试者易患2型糖尿病。然而，饮食的有益改变、体育活动增加和体重减轻可能在一定程度上逆转Ala12等位基因的致糖尿病作用，这可能是由于胰岛素敏感性提高所致。
