Timing and Variability of Maternal Hyperglycemia in Insulin‐Dependent Diabetes, Long‐Term Effects on Offspring Obesity—The TEAM Study

Abstract Objective 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. Research Design and Methods 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 A 1 concentration (where HbA 1 was represented as standard deviation units from the mean for the laboratory HBA 1 SD), and blood glucose level and variation across pregnancy, and by trimester, characterized using functional principal components (fPC). Outcomes were adult offspring BMI (kg/m 2 ), as well as visceral and whole‐body fat. Results 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 HbA 1 SD was significantly associated with offspring adiposity measures including BMI, BMI ≥ 30 kg/m 2 , 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. Conclusions 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 A 1 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.