Diabetes Associated Hla Genotypes Affect Birth Weight in the General Population. Lernmark and S-a. Ivarsson for the Dipis Study Group

" Diabetes associated HLA genotypes affect birth weight in the general population " Use of alternative location to go to the published version of the article requires journal subscription. Abstract: 246 Main text: 2880 3 Abstract Aims/hypothesis. The aim was to test the hypothesis that diabetes risk HLA-genotypes, cord blood autoantibodies or both are associated with increased birth weight. Methods. HLA-genotypes were determined in dried blood spots of cord blood from a total of 16 709 children born to healthy mothers in the Diabetes Prediction in Skåne (DiPiS) study, a population-based observational clinical investigation of newborn children. Children born to mothers with diabetes or gestational diabetes were excluded. Autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 (IA-2Ab) were determined in standard radioligand binding assays. Birth weight (BW) was adjusted for gestational age and divided into quartiles. Upper quartile was defined as high relative birth weight (HrBW) and lower quartile as low relative birth weight (LrBW). Results. Type 1 diabetes risk genotypes were strongly associated with relative birth weight (rBW) (p=0.01). The high risk HLA-DQ2/8, DQ8/0604 and DQ8/X genotypes were associated with HrBW (OR (95%CI) = 1.20 (1.08 – 1.33), p=0.0006). The type 1 diabetes negatively associated HLA-DQB1*0603 allele was also associated with HrBW (p=0.025), confirming a previous report on DQB1*0603-linked HLA-DR13. GAD65Ab were negatively associated with HrBW (OR (95%CI) = 0.72 (0.56 – 0.93), p=0.01). Regression analysis showed that the HLA associated increase in rBW was independent of confounding factors. Conclusions/interpretation. HLA-genotypes may be associated with intrauterine growth independent of type 1 diabetes risk. The epidemiological observation that high BW is a risk factor for type 1 diabetes could possibly be a result of diabetes high risk HLA moderating intrauterine growth.