Varying clinical phenotypes exist within the overarching “diagnosis” of Gestational Diabetes Mellitus (GDM), encompassing women with predominant defects in insulin sensitivity, insulin secretion or a combination of both. We aimed to determine if GDM phenotypes were independently associated with birthweight, LGA (large for gestational age), preterm delivery, caesarean delivery (CS), and a composite of GDM-related adverse pregnancy outcomes (LGA, neonatal hypoglycemia, or caesarean delivery), when adjusted for potential confounders.
Using data from OGTTs at mean gestational week 28 in the Brisbane HAPO study cohort, we estimated insulin sensitivity (Matsuda index) and secretion (HOMA β) in 1245 women. In women with GDM (10.5%, when using IADPSG criteria), defects in insulin sensitivity and/or insulin secretion were defined as <25th percentile in non-GDM women. This approach yielded four subgroups named by the predominant defect; low insulin sensitivity (GDMsens), low insulin secretion (GDMsec), both defects (GDMmixed), or no detectable defects (ND). We created linear and logistic regression models adjusted for maternal age, maternal height, BMI, smoking, gravidity, parity, family history of diabetes, mean arterial BP, and HbA1c. No women received GDM treatment during pregnancy.
Relative to non-GDM women, women in the GDMsens group (52.7% of all GDM) had higher BMI (33.8 vs 28.6 kg/m2, p<0.001), higher mean arterial BP (87 [SD 7] vs 83 [SD 7] mmHg, p<0.001), gave birth to heavier infants (birth weight z scores 0.67 [SD 1.12] vs 0.19 [SD 0.98], p<0.001) with a higher odds of LGA (OR 2.34; 95% CI 1.33, 4.12; p=0.003); had higher odds of preterm delivery (OR 2.62; 95% CI 1.14, 6.04; p=0.024), and higher odds of delivering by CS (OR 1.89; 95% CI 1.15;3.10, p=0.012). Relative to non-GDM women, women with GDMsec defects (17.6%) were older (33.6 [SD 4.5] vs 29.2 [SD 5.2] years, p<0.001), but pregnancy outcomes were similar. Relative to non-GDM women, women in the GDMmixed (14.5%) group had higher BMI (32.8 [SD 6.5] vs 28.6 [SD 5.5] kg/m2, p=0.003) and showed similar trends in outcomes to the GDMsens group, though none achieved significance. The ND women (15.3%) did not differ from non-GDM women. When adjusting for confounders including BMI, only the GDMsens group were still at increased odds for preterm delivery (OR 2.56; 95% CI 1.02, 6.46; p=0.046).After adjusting for BMI, the odds of CS and LGA babies were no longer higher in the GDMsens group. We found no increased risk of the composite GDM-related adverse pregnancy outcome in any subgroup.
Different clinical phenotypes in GDM are associated with differing risks of LGA infants, preterm delivery, and caesarean delivery. Women with GDM, predominantly due to a defect in insulin sensitivity have higher risks of adverse outcomes; only partly explained by BMI and other confounders.