Gestational diabetes: One size does not fit all-an observational study of maternal and neonatal outcomes by maternal glucose profile

ObjectivesTo examine obstetrical and neonatal outcomes across maternal glucose profiles at the population level and to explore insulin sensitivity and beta-cell function across profiles in an independent, well-phenotyped cohort for potential pathophysiologic explanation.Research Design and MethodsObservational cohort study of all pregnancies with gestational diabetes screening between October 2008 and December 2018 resulting in live singleton birth in Alberta, Canada (n = 436,773) were categorized into seven maternal glucose profiles: (1) normal 50 g-glucose challenge test (nGCT), (2) normal 75-g OGTT (nOGTT), (3) isolated elevated 1 h post-load glucose (ePLPG1), (4) isolated elevated 2 h post-load glucose (ePLPG2), (5) elevated 1 and 2 h post-load glucose (ePLPG12), (6) isolated elevated FPG (eFPG), and (7) elevated FPG + elevated 1-h and/or 2-h PLG (Combined). Primary outcomes were large for gestational age (LGA) and neonatal intensive care unit (NICU) admission rates. An independent observational cohort of 1451 women was examined for measures of beta-cell function (ISSI-2, insulinogenic index/HOMA-IR) and insulin sensitivity/resistance (Matsuda index, HOMA-IR) by similar maternal glucose profiles.ResultsPregnancies with elevated FPG, either isolated or combined, had higher adverse events and lower insulin sensitivity. The combination of elevated FPG + elevated 1-h and/or 2-h PLG had the highest rates of LGA(20.9%), NICU admissions (14.7%), and lowest insulin sensitivity as measured by Matsuda index and HOMA-IR, and beta-cell function as measured by ISSI-2 and Insulinogenic index/HOMA-IR.ConclusionsElevated fasting plasma glucose, either alone or combined with post-load glucose elevation is associated with worse outcomes than isolated post-load glucose elevation, possibly due to higher degrees of insulin resistance. Future work is needed to better understand these differences, and explore whether tailored treatment of GDM can improve neonatal outcomes.