BMI at age of 8 years is influenced by the type 2 diabetes susceptibility genes HHEX-IDE and CDKAL1.

  1. Anette-Gabriele Ziegler, MD (anziegler{at},4
  1. 1Institut fuer Diabetesforschung der Forschergruppe Diabetes e.V. at Helmholtz Center Munich, Neuherberg, Germany
  2. 2Center for Regenerative Therapies - Dresden University of Technology, Dresden, Germany
  3. 3Institute of Epidemiology, Helmholtz Center Munich, Neuherberg, Germany
  4. 4Forschergruppe Diabetes der Technischen Universitaet Muenchen, Munich, Germany


Objective: To determine whether HHEX-IDE and CDKAL1 genes which are associated with birth weight and susceptibility to type 2 diabetes continue to influence growth during childhood.

Research Design and Methods: Body mass index (BMI), weight and height at age 8 years expressed as age and gender corrected standard deviation scores (SDS) against national reference data, and single nucleotide polymorphism genotyping of HHEX-IDE and CDKAL1 loci were analyzed in 646 prospectively followed children in the German BABYDIAB cohort. All children were singleton full-term births; 386 had mothers with type 1 diabetes, 260 had fathers with type 1 diabetes and a non-diabetic mother.

Results: Type 2 diabetes risk alleles at the HHEX-IDE locus were associated with reduced BMI-SDS at age 8 years (0.17 SDS per allele; p=0.004). After stratification for birth weight, both HHEX-IDE and CDKAL1 risk alleles were associated with reduced BMI-SDS (0.45 SDS, p=0.0002; 0.52 SDS, p=0.0001) and weight-SDS (0.22 SDS, p=0.04; 0.56 SDS, p=0.0002) in children born large for gestational age (>90th centile), but not children born small or appropriate for gestational age. Within large for gestational age children, BMI and weight decreased with each additional type 2 diabetes risk allele (approximately -2 kg per allele; >8 kg overall). Findings were consistent in children of mothers with type 1 diabetes (p<0.0001) and children of non-diabetic mothers (p=0.008).

Conclusion: The type 2 diabetes susceptibility alleles at HHEX-IDE and CDKAL1 loci are associated with low BMI at age 8 years in children who were born large for gestational age.


  • Received January 21, 2010.
  • Accepted April 27, 2010.