Timing and Variability of Maternal Hyperglycemia in Insulin-Dependent Diabetes, Long-Term Effects on Offspring...

Limited data are available to describe the long-term implications of pre-pregnancy diabetes on offspring body composition in adulthood. The objective of this study was to examine the association between maternal glucose control and variation throughout pregnancy and long-term obesity in offspring. A second objective was to identify the critical windows of gestational exposure most related to the development of long-term obesity.

This cohort study included offspring of women with insulin-dependent diabetes (IDDM) who participated in the Diabetes in Pregnancy Program Project Grant (PPG) between 1978 and 1995 to evaluate the long-term implications of in utero glucose exposure. Offspring completed a comprehensive study visit which included measures of height and weight, and measures from dual-energy X-ray absorptiometry. The exposure was maternal glucose control as measured by glycohemoglobin A₁ concentration (where HbA₁ was represented as standard deviation units from the mean for the laboratory HBA₁SD), and blood glucose level and variation across pregnancy, and by trimester, characterized using functional principal components (fPC). Outcomes were adult offspring BMI (kg/m²), as well as visceral and whole-body fat.

A total of 161 offspring completed a study visit. Mean offspring age at follow-up was 32.3 years (± 4.6), 50.3% were female and 17.4% identified as Black. After adjustment for covariates (maternal age, education, family history of diabetes, diabetes severity, and BMI at last menstrual period), third-trimester maternal HbA₁SD was significantly associated with offspring adiposity measures including BMI, BMI ≥ 30 kg/m², and visceral and whole-body fat mass and percentage. The third-trimester fPC representing variability of glucose demonstrated a consistent positive association with obesity outcomes but did not reach statistical significance in adjusted models.

Our findings corroborate that the third trimester is a critical window of exposure associated with offspring adiposity. Specifically, higher levels of third-trimester maternal glycohemoglobin A₁ is a risk factor for obesity in the adult offspring of IDDM mothers. Additionally, results suggest that glucose variability may increase the risk for obesity in the adult offspring.