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Polymorphisms in the SLC2A2 (GLUT2) Gene Are Associated With the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes

The Finnish Diabetes Prevention Study

¹ Department of Medicine, University of Kuopio, Kuopio, Finland
² Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland
³ Research Department, Social Insurance Institution, Turku, Finland
⁴ Finnish Diabetes Association and Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
⁵ Department of Public Health Science and General Practice, University of Oulu, Oulu University Hospital, Oulu, Finland
⁶ Department of Sport Medicine, Oulu Deaconess Institute, Oulu, Finland
⁷ Department of Public Health, University of Helsinki, Helsinki, Finland
⁸ Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland

Impaired insulin secretion is a fundamental defect in type 2 diabetes. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the genes regulating insulin secretion (SLC2A2 [encoding GLUT2], GCK, TCF1 [encoding HNF-1], HNF4A, GIP, and GLP1R) are associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in participants of the Finnish Diabetes Prevention Study. With the exception of SLC2A2, other genes were not associated with the risk of type 2 diabetes. All four SNPs of SLC2A2 predicted the conversion to diabetes, and rs5393 (AA genotype) increased the risk of type 2 diabetes in the entire study population by threefold (odds ratio 3.04, 95% CI 1.34–6.88, P = 0.008). The risk for type 2 diabetes in the AA genotype carriers was increased in the control group (5.56 [1.78–17.39], P = 0.003) but not in the intervention group. We conclude that the SNPs of SLC2A2 predict the conversion to diabetes in obese subjects with IGT.

Abbreviations: DPS, Diabetes Prevention Study; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide 1; HNF-1, hepatocyte nuclear factor 1; IGT, impaired glucose tolerance; SNP, single nucleotide polymorphism

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