Third-trimester hyperglycemia in pregnancy linked to adult obesity in offspring

Third-trimester hyperglycemia in pregnancy linked to adult obesity in offspring | Image Credit: © lukszczepanski - stock.adobe.com.

A new analysis from the Transgenerational Effect on Adult Morbidity (TEAM) Study has found that maternal hyperglycemia in the third trimester of insulin-dependent diabetic pregnancies is associated with increased obesity risk in adult offspring, even decades later.^1,2

The study followed 161 adults born between 1978 and 1995 to mothers with insulin-dependent diabetes mellitus (IDDM), assessing the long-term effects of maternal glucose control and variability during pregnancy. These adults, now an average age of 32, participated in a detailed follow-up visit that included height, weight, and body composition assessments using dual-energy X-ray absorptiometry (DXA).

Researchers found that higher levels of maternal glycohemoglobin A1 (HbA1) in the third trimester were significantly associated with increased body mass index (BMI), greater visceral fat, and whole-body fat mass and percentage in the offspring. These associations persisted after adjusting for maternal BMI, age, education, diabetes severity, and family history of diabetes.

“Our findings corroborate that the third trimester is a critical window of exposure associated with offspring adiposity,” the authors stated. “Specifically, higher levels of third-trimester maternal glycohemoglobin A1 is a risk factor for obesity in the adult offspring of IDDM mothers.”

The study used a unique modeling method called functional principal component analysis (fPCA) to evaluate glucose patterns and variability throughout pregnancy. While consistent high glucose levels across gestation were not significantly linked to later obesity, variability in glucose levels—particularly in the third trimester—showed a consistent positive trend with higher BMI in offspring. However, this did not reach statistical significance in adjusted models.

The authors explained that increased glucose variability could stimulate fetal insulin secretion, potentially contributing to fetal fat accumulation and setting a trajectory for long-term metabolic consequences. “Results suggest that glucose variability may increase the risk for obesity in the adult offspring,” wrote the authors.

The study builds on the long-established Pedersen hypothesis, which proposed that maternal glucose crosses the placenta and affects fetal growth by stimulating insulin production. While prior research has focused largely on birth weight and early childhood obesity, this analysis provides evidence of enduring effects into adulthood.

Notably, the analysis confirmed no significant association between first- or second-trimester HbA1 levels and later-life obesity outcomes, suggesting that late pregnancy may be a particularly sensitive period for metabolic programming.

Among the 161 adult participants, 51.5% were classified as obese, and 18% had class III obesity. The researchers highlighted that the measures of third-trimester maternal HbA1 were collected at 30, 34, and 38 weeks of gestation and at delivery, capturing the final weeks of pregnancy when fetal fat stores rapidly increase.

“The TEAM Study provided the longest follow-up to date of consequences for adult offspring of women with IDDM, identifying associations with offspring outcome out to over 40 years of age,” the authors stated.

They conclude that maintaining consistent glucose control, particularly in the later stages of pregnancy, may be critical to reducing long-term obesity risk in children born to mothers with diabetes. Interventions that minimize both elevated glucose levels and fluctuations may help improve future health outcomes.

The TEAM Study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.

References:

1. Bowers K, Bhoopathy K, Szczesniak R, et al. Timing and Variability of Maternal Hyperglycemia in Insulin‐Dependent Diabetes, Long‐Term Effects on Offspring Obesity—The TEAM Study. Pregnancy. 2025;1(4). doi:https://doi.org/10.1002/pmf2.70048
2. Centers for Disease Control (CDC). National Diabetes Statistics Report. 2025. Accessed June 20, 2025. https://www.cdc.gov/diabetes/php/data-research/index.html.

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