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

Summary

In 7,970 neonates and 4,160 children from HAPO, insulin-resistant and mixed-defect GDM subtypes conferred greater risks of cord hyperinsulinemia, neonatal hypoglycemia (insulin-resistant), childhood obesity (OR 1.53), and impaired glucose tolerance (OR 2.21 and 3.01). Subtyping GDM by insulin physiology identifies offspring at highest metabolic risk.

Key Findings

• All GDM subtypes were associated with large size at birth (birth weight and skinfolds >90th percentile).
• Insulin-resistant and mixed-defect GDM increased risk of cord C-peptide >90th percentile; insulin-resistant GDM increased neonatal hypoglycemia risk.
• Childhood obesity risk was higher with insulin-resistant GDM (OR 1.53), and impaired glucose tolerance risk was elevated with insulin-resistant (OR 2.21) and mixed-defect GDM (OR 3.01).

Clinical Implications

Consider GDM subtype-based follow-up, prioritizing infants of insulin-resistant or mixed-defect GDM for early lifestyle interventions and metabolic screening into adolescence.

Limitations

• Observational design limits causal inference despite adjustments
• Subtype definitions rely on percentile cutoffs; residual confounding and center effects possible

Future Directions

Test targeted prenatal/postnatal interventions by GDM subtype; validate subtyping in diverse populations; integrate biomarkers to refine risk prediction.