Women with gestational diabetes mellitus (GDM) exhibit substantial metabolic heterogeneity, although subtype-specific differences are not routinely incorporated into clinical management. A case-control study published in Frontiers in Endocrinology evaluated glycometabolic profiles and pregnancy outcomes across GDM subtypes defined by insulin resistance and β-cell function.

The analysis included 330 women with GDM and 330 healthy controls. Using control-derived quartiles for homeostatic model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-β), participants with GDM were stratified into four subtypes: insulin resistance (GDM-IR) (36.4%), insulin secretory defect (GDM-IS) (22.7%), combined defect (GDM-M) (17.9%), and unclassified (GDM-N) (23.0%).

Findings

• The GDM-M group showed the highest first-trimester fasting glucose, all oral glucose tolerance test (OGTT) glucose values, and HbA1c levels among all subtypes.
• Cesarean delivery occurred in 72.9% of patients with GDM-M, while postpartum hemorrhage occurred in 8.5%.
• Preterm birth affected 18.6% of pregnancies in the GDM-M group, and macrosomia occurred in 17.0%.
• Neonatal hypoglycemia was reported in 11.9% of neonates born to mothers with GDM-M.
• Insulin use was highest in the GDM-M group at 18.6%, with poor glycemic control reported in 22.0%.
• Age, pre-pregnancy body mass index (BMI), GDM-IS, GDM-M, and GDM-N were independently associated with adverse pregnancy outcomes, with GDM-M showing the highest risk.

The combined-defect GDM subtype was associated with the greatest burden of adverse maternal and neonatal outcomes among the evaluated groups. These findings support the potential role of pathophysiological subtyping in pregnancy risk assessment, although interpretation is limited by the observational, single-center study design.