Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus

Diabetes Res Clin Pract. 2012 Sep;97(3):394-8. doi: 10.1016/j.diabres.2012.04.020. Epub 2012 May 14.


Aims: To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM).

Methods: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months.

Results: After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and 1.36 (1.06-1.74), respectively (additive model) versus 1.45 (1.01-2.08) and 1.56 (1.06-2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05-1.18, p=0.00016 after adjustment for age and ethnicity).

Conclusions: The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results.

MeSH terms

  • Adult
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes, Gestational / diagnosis
  • Diabetes, Gestational / epidemiology
  • Diabetes, Gestational / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Genotype
  • Glucose Tolerance Test
  • Humans
  • Polymorphism, Single Nucleotide / physiology
  • Postpartum Period
  • Pregnancy
  • Proteins / genetics
  • Puerperal Disorders / diagnosis
  • Puerperal Disorders / epidemiology
  • Puerperal Disorders / etiology
  • Puerperal Disorders / genetics*
  • Risk Factors
  • Transcription Factor 7-Like 2 Protein / genetics


  • Proteins
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human