title: Lack of association of type 2 diabetes susceptibility genotypes and body weight on the development of islet autoimmunity and type 1 diabetes.
abstract: OBJECTIVE
  To investigate whether type 2 diabetes susceptibility genes and body weight influence the development of islet autoantibodies and the rate of progression to type 1 diabetes.
  
  
  METHODS
  Genotyping for single nucleotide polymorphisms (SNP) of the type 2 diabetes susceptibility genes CDKAL1, CDKN2A/2B, FTO, HHEX-IDE, HMGA2, IGF2BP2, KCNJ11, KCNQ1, MTNR1B, PPARG, SLC30A8 and TCF7L2 was obtained in 1350 children from parents with type 1 diabetes participating in the BABYDIAB study. Children were prospectively followed from birth for islet autoantibodies and type 1 diabetes. Data on weight and height were obtained at 9 months, 2, 5, 8, 11, and 14 years of age.
  
  
  RESULTS
  None of type 2 diabetes risk alleles at the CDKAL1, CDKN2A/2B, FTO, HHEX-IDE, HMGA2, IGF2BP2, KCNJ11, KCNQ1, MTNR1B, PPARG and SLC30A8 loci were associated with the development of islet autoantibodies or diabetes. The type 2 diabetes susceptible genotype of TCF7L2 was associated with a lower risk of islet autoantibodies (7% vs. 12% by age of 10 years, P = 0.015, P(corrected) = 0.18). Overweight children at seroconversion did not progress to diabetes faster than non-overweight children (HR: 1.08; 95% CI: 0.48-2.45, P>0.05).
  
  
  CONCLUSIONS
  These findings do not support an association of type 2 diabetes risk factors with islet autoimmunity or acceleration of diabetes in children with a family history of type 1 diabetes.
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Winkler
authors.forename: Jennifer
authors.initials: J
authors.lastname: Raab
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Anette-Gabriele
authors.initials: AG
authors.lastname: Ziegler
mesh_terms: D000293:Adolescent; D015551:Autoimmunity / Q000276:immunology*; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018709:Statistics, Nonparametric; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics
chemical_list: C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein