1400-P: Adverse Perinatal and Long-Term Outcomes Differ among Physiologic Subtypes of Gestational Glucose Intolerance

Background: Gestational diabetes mellitus (GDM) is associated with adverse perinatal and long-term outcomes; it is unclear if these outcomes are equally distributed among all affected women. We aimed to define physiologic subtypes of gestational glucose intolerance using beta-cell (BC) function and insulin sensitivity (IS) parameters and characterize adverse outcomes associated with each subtype.

Methods: We used homeostasis model assessment to estimate BC function and IS from fasting glucose and insulin levels at 16-20 weeks gestation. We defined BC and IS defects using the 50^th percentile in 1369 women with normal subsequent 50g glucose load tests (GLTs, performed at 24-30 weeks gestation). We categorized 158 women whose GLTs were abnormal (1-hour glucose ≥130 mg/dl) according to the predominant physiologic defect. We compared hyperglycemia-associated adverse outcomes across physiologic subtypes. We used logistic regression to adjust for potential confounders.

Results: Among 158 women, 59 (37%) had BC defects, 83 (53%) had IS defects, 10 (6%) had both, 6 (4%) had neither. Women with IS defects (vs. those with BC defects) were more likely develop GDM (13% vs. 2% by Carpenter-Coustan criteria, P=0.03), while women with BC defects were more likely to develop pregnancy-associated hypertension (20% vs. 7%, P=0.02). Women with IS defects (vs. women with BC defects) were more likely to develop postpartum glucose intolerance (prediabetes/type 2 diabetes) (29% vs. 3%, P<0.001) during a mean follow-up of 12 years. Differences persisted after adjustment for BMI, age, and GDM. There were no differences in other pre-specified outcomes (macrosomia, cesarean delivery, neonatal intensive care unit admission) across subtypes.

Conclusion: Distinct underlying physiologic mechanisms leading to gestational glucose intolerance are associated with distinct hyperglycemia-associated adverse outcomes. This may inform risk stratification and allow for targeted management approaches.