Infertility, Gravidity, and Risk Of Diabetes among High-Risk Women in the Diabetes Prevention Program Outcomes Study

J Clin Endocrinol Metab. 2020 Mar 1;105(3):e358-e367. doi: 10.1210/clinem/dgaa013.


Objective: The extent to which infertility and pregnancy independently increase risk of diabetes and subclinical atherosclerosis is not known.

Research design and methods: We conducted a secondary analysis of Diabetes Prevention Program (DPP) and the DPP Outcomes Study over a 15-year period. We included women who answered questions about gravidity and infertility at baseline (n = 2085). Infertility was defined as > 1 year of unsuccessful attempts to conceive; thus, women could have histories of infertility as well as pregnancy. Risk of diabetes associated with gravidity and infertility was calculated using Cox proportional hazards models adjusting for age, race/ethnicity, treatment arm, body mass index, and pregnancy during the study. Among women who underwent assessment of coronary artery calcification (CAC) (n = 1337), odds of CAC were calculated using logistic regression models with similar covariates.

Results: Among premenopausal women (n = 1075), women with histories of pregnancy and infertility (n = 147; hazard ratio [HR] 1.80; 95% confidence interval [CI] 1.30, 2.49) and women with histories of pregnancy without infertility (n = 736; HR 1.49; 95% CI 1.15, 1.93) had greater diabetes risk than nulligravid women without infertility (n = 173). Premenopausal nulligravid women with histories of infertility had a non-significant elevation in risk, although the number of these women was small (n = 19; HR 1.63; 95% CI 0.88, 3.03). Associations were not observed among postmenopausal women (n = 1010). No associations were observed between infertility or pregnancy with CAC.

Conclusions: Pregnancy, particularly combined with a history of infertility, confers increased risk of diabetes but not CAC among glucose-intolerant premenopausal women.

Trial registration: NCT00038727.

Keywords: coronary artery calcification; diabetes; infertility; pregnancy.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / etiology*
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Female
  • Gravidity / physiology*
  • Humans
  • Incidence
  • Infertility, Female / complications
  • Infertility, Female / epidemiology*
  • Life Style
  • Metformin / therapeutic use
  • Middle Aged
  • Pregnancy
  • Preventive Health Services* / methods
  • Preventive Health Services* / statistics & numerical data
  • Primary Prevention / methods
  • Primary Prevention / organization & administration
  • Risk Factors
  • Risk Reduction Behavior
  • Treatment Outcome
  • United States / epidemiology


  • Metformin

Associated data