Long-Term Effects of Maternal Glycemic Measures in Pregnancy and Offspring Adverse Glycemic Outcomes: Results from the TEAM Study

Objective: In utero exposure to maternal prepregnancy diabetes is associated with an increased risk for abnormal glycemic outcomes in children, including impaired glucose tolerance, insulin resistance, and type 2 diabetes. Our objective was to evaluate the timing of exposure to maternal dysglycemia and whether the effects persist into adulthood. Study Design: The Transgenerational Effects on Adult Morbidity (TEAM) Study followed offspring of mothers with prepregnancy insulin-dependent diabetes mellitus (IDDM), who participated in a Program Project Grant (PPG) between 1978 and 1995. These women had a detailed characterization of glycemic measures across pregnancy and comprehensive obstetric and delivery data. Offspring participated in a complete clinical exam, which included an oral glucose tolerance test (OGTT). Multiple regression methods were used to identify associations between trimester-specific maternal hemoglobin A1 (HbA1) standard deviation (HbA1SD) and maternal glucose profiles with offspring glycemic outcomes, adjusting for covariates. Results: SD was associated with increased offspring fasting plasma glucose and HbA1c ≥6.5% after adjusting for maternal age, family history of diabetes, presence of microvascular disease, and body mass index (BMI) at the last menstrual period. Both second- and third-trimester maternal HbA1SD were positively associated with offspring HbA1c and inversely associated with the acute insulin response to glucose (AIRg), defined as the rapid, first-phase release of insulin from pancreatic beta-cells within 10 minutes of the OGTT. Conclusion: Our findings add to the current literature showing that the association between trimester-specific gestational maternal glycemic status and offspring adverse glycemic outcome persists into adulthood in the offspring. Key Points: · Exposure to maternal IDDM is associated with offspring glycemic outcomes.. · Maternal glycohemoglobin, particularly in the first trimester, is associated with HbA1c and fasting glucose.. · Mid-late pregnancy hyperglycemia was associated with reduced offspring acute insulin response..