Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes. |
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| Authors: | O Laukkanen J Pihlajamäki J Lindström J Eriksson T T Valle H Hämäläinen P Ilanne-Parikka S Keinänen-Kiukaanniemi J Tuomilehto M Uusitupa M Laakso |
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| Institution: | (1) Department of Medicine, University of Kuopio, 70210 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 and Department of Sport Medicine, Oulu Deaconess Institute, Oulu, Finland;(6) Department of Public Health, University of Helsinki, Helsinki, Finland;(7) Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland |
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| Abstract: | Aims/hypothesis Type 2 diabetes is a complex disorder with strong heritability. The aim of our study was to investigate whether common polymorphisms in the genes regulating the early insulin signalling pathway (insulin; A-23T, insulin-like growth factor 1 receptor IGF-1R]; GAG1013GAA, plasma cell membrane glycoprotein 1 PC-1]; K121Q, insulin receptor substrate IRS-1]; G972R, insulin receptor substrate 2 IRS-2]; G1057D and phosphatidylinositol 3-kinase p85 PI3K]; M326I) affect the weight change and development of Type 2 diabetes in the Finnish Diabetes Prevention Study.Methods We screened for the polymorphisms in 490 overweight subjects with impaired glucose tolerance whose DNA was available from the Finnish Diabetes Prevention Study. These subjects were randomly allocated into a control group and an intervention group characterised by intensive, individualised diet and exercise.Results In carriers of the GAA1013GAA genotype of IGF-1R, the R972 allele of IRS-1 and the D1057D genotype of IRS-2, lifestyle intervention did not lead to significant differences in weight loss between the intervention and control groups, implying a role of these risk genotypes in the regulation of body weight. We observed a statistically significant difference in the conversion rate from IGT to diabetes between the genotypes of the IGF-1R gene (GAG1013GAG: 18.6%, GAG1013GAA: 10.4%, GAA1013GAA: 19.5%, p=0.033). Common polymorporphisms in the insulin, PC-1 and PI3K genes did not regulate weight change or conversion to diabetes.Conclusions/interpretation The common polymorphisms of the IGF-1R, IRS-1 and IRS-2 genes may modify the weight change response to a lifestyle intervention but not the conversion from IGT to Type 2 diabetes, whereas IGF-1R may also regulate the risk of developing Type 2 diabetes.Abbreviations DPS Finnish Diabetes Prevention Study - IGF-1R insulin-like growth factor 1 receptor - PC-1 plasma cell membrane glycoprotein-1 - PI3K phosphatidylinositol 3-kinase - PI3K p85 phosphatidylinositol 3-kinase regulatory subunit p85 - PPAR peroxisome proliferator-activated receptor - VNTR variable number of tandem repeat |
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| Keywords: | Genes Impaired glucose tolerance Insulin Insulin signalling Prevention Type 2 diabetes Weight change |
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