AIMS/HYPOTHESIS: Associations have been described between higher birthweight and increased risk of type 1 diabetes, and of insulin (INS) and human leucocyte antigen (HLA) genotypes that protect against diabetes with larger size at birth. We studied simultaneously the effects of size at birth, INS and HLA genotypes on the risk of type 1 diabetes to test whether the relation between size at birth and risk of type 1 diabetes would be strengthened after adjustment for INS and HLA genotypes. SUBJECTS AND METHODS: We designed a population-based case-control study in Norway with 471 cases of childhood-onset type 1 diabetes and 1,369 control subjects who were genotyped for the INS -23HphI polymorphism (surrogate for INS variable number of tandem repeats) and HLA-DQ alleles associated with type 1 diabetes. Data on birthweight and other perinatal factors were obtained from the Medical Birth Registry of Norway by record linkage. RESULTS: The data fitted a multiplicative model for the protective INS class III allele both within the INS locus and for the model with INS- and HLA-DQ-conferred risk of type 1 diabetes. We found no overall significant association between weight or head circumference at birth and the risk of type 1 diabetes, and adjustment for INS and HLA genotype did not influence this result. There was also no evidence for association of INS or HLA with size at birth among control subjects. CONCLUSIONS/ INTERPRETATION: In contrast to suggestions from previous indirect studies, direct adjustment for INS and HLA genotypes did not lead to a stronger relation between birthweight and the risk of type 1 diabetes.
AIMS/HYPOTHESIS: Associations have been described between higher birthweight and increased risk of type 1 diabetes, and of insulin (INS) and human leucocyte antigen (HLA) genotypes that protect against diabetes with larger size at birth. We studied simultaneously the effects of size at birth, INS and HLA genotypes on the risk of type 1 diabetes to test whether the relation between size at birth and risk of type 1 diabetes would be strengthened after adjustment for INS and HLA genotypes. SUBJECTS AND METHODS: We designed a population-based case-control study in Norway with 471 cases of childhood-onset type 1 diabetes and 1,369 control subjects who were genotyped for the INS -23HphI polymorphism (surrogate for INS variable number of tandem repeats) and HLA-DQ alleles associated with type 1 diabetes. Data on birthweight and other perinatal factors were obtained from the Medical Birth Registry of Norway by record linkage. RESULTS: The data fitted a multiplicative model for the protective INS class III allele both within the INS locus and for the model with INS- and HLA-DQ-conferred risk of type 1 diabetes. We found no overall significant association between weight or head circumference at birth and the risk of type 1 diabetes, and adjustment for INS and HLA genotype did not influence this result. There was also no evidence for association of INS or HLA with size at birth among control subjects. CONCLUSIONS/ INTERPRETATION: In contrast to suggestions from previous indirect studies, direct adjustment for INS and HLA genotypes did not lead to a stronger relation between birthweight and the risk of type 1 diabetes.
Authors: Simon M S Mitchell; Andrew T Hattersley; Beatrice Knight; Tina Turner; Bradley S Metcalf; Linda D Voss; David Davies; Anne McCarthy; Terence J Wilkin; George Davey Smith; Yoav Ben-Shlomo; Timothy M Frayling Journal: J Clin Endocrinol Metab Date: 2004-01 Impact factor: 5.958
Authors: Robert S Lindsay; Robert L Hanson; Chris Wiedrich; William C Knowler; Peter H Bennett; Leslie J Baier Journal: Diabetes Date: 2003-01 Impact factor: 9.461
Authors: C R Cardwell; L C Stene; G Joner; E A Davis; O Cinek; J Rosenbauer; J Ludvigsson; C Castell; J Svensson; M J Goldacre; T Waldhoer; J Polanska; S G A Gimeno; L-M Chuang; R C Parslow; E J K Wadsworth; A Chetwynd; P Pozzilli; G Brigis; B Urbonaite; S Sipetić; E Schober; C Ionescu-Tirgoviste; C E de Beaufort; D Stoyanov; K Buschard; C C Patterson Journal: Diabetologia Date: 2010-01-10 Impact factor: 10.122
Authors: M Bjørnvold; D E Undlien; G Joner; K Dahl-Jørgensen; P R Njølstad; H E Akselsen; K Gervin; K S Rønningen; L C Stene Journal: Diabetologia Date: 2008-02-22 Impact factor: 10.122