Genetic Risk of Progression to Type 2 Diabetes and Response to Intensive Lifestyle or Metformin in Prediabetic Women With and Without a History of Gestational Diabetes Mellitus

  1. for the Diabetes Prevention Program Research Group*
  1. 1Endocrine Division, Department of Medicine, MedStar Washington Hospital Center, Washington, DC
  2. 2The Biostatistics Center, The George Washington University, Rockville, MD
  3. 3Center for Human Genetic Research and Diabetes Research Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, MA
  4. 4Program in Medical and Population Genetics, Broad Institute, Cambridge, MA
  5. 5Department of Medicine, Harvard Medical School, Boston, MA
  6. 6Department of Epidemiology, Colorado School of Public Health, Aurora, CO
  7. 7Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden
  8. 8Department of Nutrition, Harvard School of Public Health, Boston, MA
  9. 9Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
  10. 10Division of Endocrinology, Diabetes, and Metabolism, University of Tennessee Health Science Center, Memphis, TN
  11. 11Department of Medicine and Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI
  12. 12National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ
  13. 13American Diabetes Association, Alexandria, VA
  1. Corresponding author: Shannon D. Sullivan, dppmail{at}


OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births.

RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM.

RESULTS β-Cell function was reduced in women with GDM. The GRS was positively associated with a history of GDM; however, the GRS did not predict progression to diabetes or modulate response to intervention.

CONCLUSIONS These data suggest that a diabetes-associated GRS is associated with development of GDM and may characterize women at risk for development of diabetes due to β-cell dysfunction.


  • Received March 22, 2013.
  • Accepted August 18, 2013.

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  1. Diabetes Care vol. 37 no. 4 909-911
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