Purpose: The 12Glu9 polymorphism of the α2B-adrenergic receptor gene may impair insulin secretion and modify the effects of a lifestyle intervention on the risk of type 2 diabetes, but the interaction with specific lifestyle components is unknown. We assessed the associations of leisure-time physical activity (LTPA), dietary changes, and weight loss on the risk of type 2 diabetes according to the 12Glu9 polymorphism in 481 participants of the Finnish Diabetes Prevention Study.
Methods and Results: The lifestyle intervention decreased the risk of diabetes in 9Glu carriers (9Glu9, intervention vs control, relative risk (RR) = 0.23, 95% confidence interval (CI) 0.09-0.62), but not in 12Glu12 homozygotes. In the combined intervention and control groups, increased total LTPA as estimated with a questionnaire decreased the risk of diabetes in 12Glu carriers (12Glu12, upper vs lower third, RR = 0.12, 95% CI 0.03-0.53) but not in 9Glu9 homozygotes (P for the interaction 0.033). In contrast, favorable dietary changes, estimated using a dietary score, reduced the risk of diabetes in those with the 9Glu9 genotype (upper vs lower third, RR = 0.21, 95% CI 0.06-0.75) but not in those with the 12Glu allele. Weight loss significantly decreased the risk of diabetes only in 12Glu carriers.
Conclusion: Increased LTPA decreased the risk of type 2 diabetes more in those with the 12Glu allele of the ADRA2B gene, whereas dietary changes may have mediated the greater risk reduction of the lifestyle intervention in 9Glu homozygotes.
1Department of Medicine, Kuopio University Hospital; Departments of 2Physiology and 3Clinical Nutrition, University of Kuopio, Kuopio, FINLAND; 4Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute; 5Department of Public Health, University of Helsinki, Helsinki, FINLAND
Address for correspondence: Matti Uusitupa, M.D., Ph.D., Department of Clinical Nutrition and Food and Health Research Center, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland; E-mail: Matti.Uusitupa@uku.fi.
Submitted for publication June 2006.
Accepted for publication September 2006.