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

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. 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. Among 161 offspring up to 42 years of age (mean age, 32.3 years), first trimester HbA1SD 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. 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.