Adverse pregnancy outcomes and risk of type 2 diabetes in postmenopausal women

Abstract

Background: Although gestational diabetes mellitus and delivering high-birthweight infants are known to predict a higher risk of future type 2 diabetes mellitus, the association of hypertensive disorders of pregnancy and other adverse pregnancy outcomes with type 2 diabetes mellitus is not well established.

Objective: This study aimed to examine the associations between different types of adverse pregnancy outcomes and incident type 2 diabetes mellitus among postmenopausal women.

Study design: The Women's Health Initiative, a nationwide cohort of postmenopausal women, collected self-reported history of adverse pregnancy outcomes, including gestational diabetes mellitus, hypertensive disorders of pregnancy, preterm birth, and delivering low- birthweight (<2500 g) or high-birthweight (>4500 g) infants. Participants were followed up annually for self-reported incident type 2 diabetes mellitus treated with medication from baseline (1993-1998) to March 2021. This study used logistic regression to examine the associations of any and individual adverse pregnancy outcomes with diabetes mellitus. Stratified analyses were performed to assess effect modification by body mass index, race and ethnicity, education, parity, breastfeeding, and age at first birth.

Results: This analysis included 49,717 women without a history of diabetes mellitus at enrollment who had a least 1 pregnancy and responded to the questionnaire about adverse pregnancy outcomes. After adjusting for body mass index, demographic, lifestyle, and reproductive factors, gestational diabetes mellitus (odds ratio, 2.26; 95% confidence interval, 1.94-2.63), high birthweight (odds ratio, 1.30; 95% confidence interval, 1.18-1.44), and hypertensive disorders of pregnancy (odds ratio, 1.18; 95% confidence interval, 1.08-1.30) were independently associated with higher odds of type 2 diabetes mellitus, whereas preterm birth and low birthweight were not associated with diabetes mellitus risk. A history of ≥2 adverse pregnancy outcomes was associated with higher odds of type 2 diabetes mellitus (odds ratio, 1.55; 95% confidence interval, 1.28-1.88). This study further observed higher odds of type 2 diabetes mellitus (odds ratio, 3.69; 95% confidence interval, 2.38-5.70) among women with a history of both gestational diabetes mellitus and hypertensive disorders of pregnancy than those without any adverse pregnancy outcomes.

Conclusion: Postmenopausal women with a history of gestational diabetes mellitus, those delivering high-birthweight infants, or those with hypertensive disorders of pregnancy are at risk of future type 2 diabetes mellitus. In addition, women with ≥2 conditions had an augmented risk and might be prioritized for screening and prevention efforts for type 2 diabetes mellitus.

Keywords: diabetes mellitus; gestational diabetes mellitus; high birthweight; hypertensive disorders of pregnancy.

FIGURE 1. Flowchart of the selection of study participants from the WHI study

APO, adverse pregnancy outcome; T2D, type 2 diabetes mellitus; WHI, Women’s Health Initiative. Zhu. Adverse pregnancy outcomes and future diabetes risk. Am J Obstet Gynecol 2023.

FIGURE 2. Associations between GDM, with or without other APOs, and T2D

“No APO” referred to answering “no” to any APO questions without answering “yes” to other APO questions. All models were adjusted for age at enrollment (continuous), race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and other), education (high school or below, some college, and college and above), annual family income (<$20,000, $20,000–$74,900, and ≥$75,000), body mass index (continuous), physical activity (continuous), age at menarche (≤11, 12–13, and ≥14 years), parity (0–1, 2, 3, 4, and ≥5), age at first birth (never had term pregnancy, <20, 20–29, and ≥30 years), and age at menopause (continuous). APO, adverse pregnancy outcome; CI, confidence interval; GDM, gestational diabetes mellitus; HBW, high birthweight; HDP, hypertensive disorder of pregnancy; LBW, low birthweight; OR, odds ratio PTB, preterm birth. Zhu. Adverse pregnancy outcomes and future diabetes risk. Am J Obstet Gynecol 2023.