Gestational Diabetes Subtypes and Their Distinct Effects on Metabolic Outcomes in Offspring

All subtypes of gestational diabetes mellitus (GDM) are associated with increased birth weight and greater newborn adiposity compared to mothers with normal glucose tolerance. Insulin-resistant GDM, characterized by impaired insulin sensitivity, was specifically associated with elevated cord C-peptide levels, neonatal hypoglycemia, and a higher risk of childhood obesity and impaired glucose tolerance. These findings were recently published in the journal Diabetes Care.1

The study examined subtypes of GDM based on insulin sensitivity and secretion and their impact on newborn and childhood outcomes, both anthropometric and glycemic. Data for the analysis was obtained from the Hyperglycemia and Adverse Pregnancy Outcome Study (HAPO) and Follow-Up Study and involved 7970 and 4160 mother-offspring dyads, respectively.

GDM was categorized as insulin-deficient (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). Among the 7970 mothers, 1241 (15.6%) were diagnosed with gestational diabetes mellitus (GDM). Of these, 289 (23.3%) had insulin-deficient GDM, 742 (59.8%) had insulin-resistant GDM, 131 (10.6%) had mixed-defect GDM, and 79 (6.4%) had unclassified GDM.

Results showed that all the three GDM subtypes were linked to increased birth weight and skinfold thickness (>90th percentile). Insulin-resistant and mixed-defect GDM were associated with elevated cord C-peptide levels >90th percentile. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia. Insulin-resistant GDM was linked to a 1.5 times higher risk of neonatal hypoglycemia and childhood obesity with odds ratio (OR) of 1.53.

Insulin-resistant GDM more than doubled the risk of childhood impaired glucose tolerance (OR 2.21), while mixed-defect GDM showed the highest risk for impaired glucose tolerance in children with OR of 3.01.

The study highlights the importance of more accurate characterization of women with GDM to better identify offspring at higher risk for adverse short- and long term metabolic outcomes. By identifying mothers with insulin-resistant or mixed-defect GDM, targeted preventative interventions could be initiated early in life to reduce the risk of childhood obesity and impaired glucose tolerance.

Reference

1.   Meredith E Osmulski, et al. Subtypes of gestational diabetes mellitus are differentially associated with newborn and childhood metabolic outcomes. Diabetes Care. 2025 Jan 9:dc241735. doi: 10.2337/dc24-1735.