Subtypes of Gestational Diabetes Mellitus Are Differentially Associated With Newborn and Childhood Metabolic Outcomes

Objective: Subtypes of gestational diabetes mellitus (GDM) based on insulin sensitivity and secretion have been described. We addressed the hypothesis that GDM subtypes are differentially associated with newborn and child anthropometric and glycemic outcomes. Research design and methods: Newborn and child (age 11-14 years) outcomes were examined in 7,970 and 4,160 mother-offspring dyads, respectively, who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and HAPO Follow-Up Study. GDM was classified as insulin-deficient GDM (insulin secretion <25th percentile with preserved insulin sensitivity), insulin-resistant GDM (insulin sensitivity <25th percentile with preserved insulin secretion), or mixed-defect GDM (both <25th percentile). Regression models for newborn and child outcomes included adjustment for field center, maternal BMI, and other pregnancy covariates. Child models also included adjustment for child age, sex, and family history of diabetes. Results: Compared with mothers with normal glucose tolerance, all three GDM subtypes were associated with birth weight and sum of skinfolds >90th percentile. Insulin-resistant and mixed-defect GDM were associated with higher risk of cord C-peptide levels >90th percentile. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia and childhood obesity (odds ratio [OR] 1.53, 95% CI 1.127-2.08). The risk of childhood impaired glucose tolerance was higher with insulin-resistant GDM (OR 2.21, 95% CI 1.50-3.25) and mixed-defect GDM (OR 3.01, 95% CI 1.47-6.19). Conclusions: GDM subtypes are differentially associated with newborn and childhood outcomes. Better characterizing individuals with GDM could help identify at-risk offspring to offer targeted, preventative interventions early in life.