Women with gestational glucose intolerance, defined as an abnormal initial gestational diabetes screening test, are at risk for adverse pregnancy outcomes even if they do not have gestational diabetes. We previously defined gestational diabetes physiologic subtypes based on the primary underlying physiology leading to hyperglycemia and found that women with different subtypes had differential risk of adverse outcomes. Physiologic subclassification has not yet been applied to women with gestational glucose intolerance.
We defined gestational glucose intolerance physiologic subtypes based on the presence of insulin resistance, insulin deficiency, or mixed pathophysiology, and aimed to determine if these subtypes are at differential risk for adverse outcomes. We hypothesized that women with the insulin resistant subtype of gestational glucose intolerance would have the greatest risk of adverse pregnancy outcomes.
In a hospital-based cohort study, we studied women with gestational glucose intolerance (glucose loading test 1-hour glucose ≥140 mg/dL, N=236) and normal glucose tolerance (glucose loading test 1-hour glucose <140 mg/dL, N=1472). We applied homeostasis model assessment to fasting glucose and insulin levels at 16-20 weeks' gestation to assess insulin resistance and deficiency and used these measures to classify women with gestational glucose intolerance into subtypes. We compared odds of adverse outcomes (large for gestational age birthweight, neonatal intensive care unit admission, pregnancy-related hypertension, cesarean delivery) in each subtype to odds in women with normal glucose tolerance using logistic regression with adjustment for age, race/ethnicity, marital status, and body mass index.
Of women with gestational glucose intolerance (12% with gestational diabetes), 49% had the insulin resistant subtype (N=115), 27% had the insulin deficient subtype (N=70), 17% had the mixed pathophysiology subtype (N=40), and 5% were uncategorized (N=11). We found increased odds of large for gestational age birthweight (primary outcome), in women with the insulin resistant subtype compared to women with normal glucose tolerance (OR 2.35 [1.43-3.88], p=0.001; adjusted OR 1.74 [1.02-3.48], p=0.04). The odds of large for gestational age birthweight in women with the insulin deficient subtype were increased only after adjustment for covariates (OR 1.69 [0.84-3.38], p=0.14; adjusted OR 2.05 [1.01-4.19], p=0.048). Among secondary outcomes, there was a trend toward increased odds of neonatal intensive care unit admission in the insulin resistant subtype in an unadjusted model (OR 2.09 [0.99-4.40], p=0.05); this finding was driven by an increased risk of neonatal intensive care unit admission in women with the insulin resistant subtype and body mass index <25 kg/m. Infants of women with other subtypes did not have increased odds of neonatal intensive care unit admission. The odds of pregnancy-related hypertension in the insulin resistant subtype were increased (OR 2.09 [1.31-3.33], p=0.002; adjusted OR 1.77 [1.07-2.92], p=0.03) compared to women with normal glucose tolerance; other subtypes did not have increased odds of pregnancy-related hypertension. There was no difference in cesarean delivery rates in nulliparous women across subtypes.
Insulin resistant gestational glucose intolerance is a high-risk subtype for adverse pregnancy outcomes. Delineating physiologic subtypes may provide opportunities for a more personalized approach to gestational glucose intolerance.