Heterogeneity of Gestational Diabetes and Risk for Adverse Pregnancy Outcome: A Cohort Study

Context: Diabetes is increasingly recognized as a heterogeneous disease, with clinical characteristics and outcome risks varying across different phenotypes. Evidence on heterogeneity of gestational diabetes (GDM) is yet to be provided. Objective: To investigate the insulin physiology and pregnancy outcomes of GDM phenotypes characterized by fasting hyperglycemia or postload hyperglycemia. Methods: A total of 2050 women who underwent a 75-g oral glucose tolerance test were prospectively recruited and followed until delivery. Women were categorized into normoglycemia (NGT, n = 936), isolated impaired fasting glucose (gestational-IFG, n = 378), and isolated impaired postload glucose tolerance (gestational-IGT, n = 736) groups. Fasting blood samples at mid-pregnancy were collected to measure C-peptide and insulin concentrations. Homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were used to evaluate insulin physiology. Maternal and neonatal outcomes were recorded. Results: Gestational-IFG had greater insulin resistance (HOMA-IR 3.11 vs 2.25, QUICKI-C-peptide 0.94 vs 1.03, both P < .01), and gestationalIGT had worse (3-cell function (C-peptide 2.00 vs 2.26 ng/mL, P < .05), when compared to one another. Gestational-IFG was more strongly associated with excessive gestational weight gain (risk ratio ERR] 1.62; 95% CI, 1.18-2.23) and large-for-gestational-age infants (RR 1.45; 95% CI, 1.03-2.03) than gestational-IGT. The risk for neonatal brain injury was increased in gestational-IGT (RR 2.03; 95% CI, 1.04-4.09), but not in gestational-IFG (P = .439). Gestational-IGT showed a stronger association with the risk of preterm birth compared to gestational-IFG (RR 1.80; 95% CI, 1.02-3.36). Conclusion: GDM exhibits distinct insulin physiology profiles. Pregnancy outcome varies between each phenotype. These findings provide evidence on risk stratification and diverse strategies for the treatment of GDM.