Women With Gestational Diabetes Have Elevated 30-Year Mortality Risk, Study Suggests

Individuals with a history of gestational diabetes have a slightly elevated risk of subsequent mortality over a 30-year period compared with individuals without a history, a new study published in JAMA Internal Medicine suggests.

This finding is based on a cohort study of more than 91,000 participants of the Nurses’ Health Study II, with a 30-year follow-up between 1989 and 2019.

The study included US female nurses aged 25 to 42 years with a mean (SD) aged of 34.9 (4.7) years. All women in the study reported at least 1 pregnancy lasting at least 6 months during adulthood, and the mean body mass index (BMI) at baseline was 24.1 (4.7). Across more than 2.6 million person-years, there were 3937 recorded deaths, including 255 caused by cardiovascular disease (CVD) and 1397 caused by cancer. All findings had a CI of 95%.

The study investigators found that individuals who reported a history of gestational diabetes were 1.28 (1.13-1.44) times more likely to experience mortality over the next 30 years, with a higher crude mortality rate of 1.74 per 1000 person-years compared with 1.49 for those without a history of gestational diabetes. After further adjusting for potential confounders and lifestyle factors during women’s reproductive years, the risk did not drastically change (HR, 1.25; 1.11-1.41).

Interestingly, this association persisted regardless of whether women developed type 2 diabetes (T2D) following their pregnancy. Less-healthy lifestyle factors also contributed to this association, including:

• Low-quality diet, defined as an Alternative Healthy Eating Index score in the bottom 60% (HR, 1.32; 1.15-1.52)
• Smoking 20 or more cigarettes per day (HR, 1.40; 1.01-1.94)
• Overweight or obesity, defined as a BMI of 25 or more (HR, 1.37; 1.19-1.58)
• Low physical activity levels, defined as less than 30 minutes per day (HR, 1.31; 1.15-1.50)
• Consuming non-moderate amounts of alcohol, defined as <5 or >15 grams per day (HR, 1.31; 1.12-1.51)
• Hypercholesterolemia (HR, 1.35; 1.16-1.58)
• Chronic hypertension (HR, 1.24; 1.05-1.46)
• CVD history (HR, 1.52; 1.00-2.32)

Associations were also stronger for women who:

• Had gestational diabetes in 2 or more pregnancies (HR, 1.48; 0.99-2.19)
• Had gestational diabetes during both their first and subsequent pregnancies (HR, 1.71; 1.11-2.63)
• Also reported hypertensive disorders in pregnancy (HR, 1.80; 1.21-2.67), preterm birth (HR, 2.46; 1.66-3.64), or low birth weight (HR, 2.11; 1.21-3.68)

Additionally, cause-specific mortality analyses revealed that gestational diabetes was directly associated with risk of CVD-associated mortality (HR, 1.59; 1.03-2.47). Meanwhile, gestational diabetes was inversely associated with cancer mortality (HR, 0.76; 0.59-0.98), but this was only evident among women who later developed T2D.

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“Results from the cause-specific proportional hazards models suggest that this inverse association is unlikely to be associated with the competing risk of mortality from other causes,” the investigators said. “Instead, it could be partly explained by early detection, management of medical conditions, and lifestyle interventions (eg, BMI reduction or maintenance, healthy diet, and physical activity) that are often recommended to patients with T2D.”

The study has several limitations that are important to note. First, self-reported gestational diabetes could potentially introduce exposure misclassification, although it's considered highly accurate in this study population. Second, the predominance of non-Hispanic White participants as well as the limited number of non-CVD or non-cancer deaths may limit the generalizability of the findings. Additionally, the study lacked data on prediabetes, gestational diabetes onset age, and disease severity, and the study’s observational design prevented the investigators from making any causal associations.

“The findings emphasize the importance for health care professionals to consider gestational diabetes as a critical factor when evaluating the later-life mortality risk of their patients,” the investigators concluded.

Reference

Wang YX, Mitsunami M, Manson JE, et al. Association of gestational diabetes with subsequent long-term risk of mortality. JAMA Intern Med. Published online September 11, 2023. doi:10.1001/jamainternmed.2023.4401