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

Catherine Kim, Naji Younes, Marinella Temprosa, Sharon Edelstein, Ronald B Goldberg, Maria G Araneta, Amisha Wallia, Angela Brown, Christine Darwin, Uzoma Ibebuogu, Xavier Pi-Sunyer, William C Knowler

Journal: The Journal of clinical endocrinology and metabolism 2020;105(3):e358-67

PMID: 31955207

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Abstract

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.

Address: Departments of Medicine, Obstetrics & Gynecology, and Epidemiology, University of Michigan, Ann Arbor, Michigan.; Biostatistics Center, George Washington University, Rockville, Maryland.; Department of Epidemiology & Biostatistics, George Washington University, Washington, DC.; Department of Medicine, University of Miami, Miami, Florida.; Department of Family and Preventive Medicine, University of California, San Diego, California.; Department of Medicine, Northwestern University, Chicago, Illinois.; Department of Medicine, Washington University, St. Louis, Missouri.; Department of Medicine, University of California, Los Angeles, California.; Department of Medicine, University of Tennessee, Memphis, Tennessee.; Department of Medicine, Columbia University College of Physicians and Surgeons, New York City, New York.; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Phoenix, Arizona.

DOI: 10.1210/clinem/dgaa013

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MeSH Terms: Adult, Aged, Diabetes Mellitus, Type 2, Female, Gravidity, Humans, Incidence, Infertility, Female, Life Style, Metformin, Middle Aged, Pregnancy, Preventive Health Services, Primary Prevention, Risk Factors, Risk Reduction Behavior, Treatment Outcome, United States