To evaluate changes in insulin physiology in euglycemic pregnancy and gestational diabetes mellitus (GDM).
Participants underwent oral glucose tolerance tests at ≤15 weeks’ gestation (early pregnancy), 24–32 weeks’ gestation (mid-late pregnancy), and 6–24 weeks postpartum. We evaluated longitudinal changes in insulin secretory response (log Stumvoll first-phase estimate) and insulin sensitivity (log Matsuda index) using linear mixed models. We then evaluated participants who met GDM criteria in early pregnancy (early GDM) and mid-late pregnancy (classic GDM) separately from those without GDM. We derived the pregnancy insulin physiology (PIP) index to quantify β-cell compensation for insulin resistance.
Among 166 participants, 21 had early GDM and 24 developed classic GDM. Insulin sensitivity was reduced slightly in early pregnancy (β = −0.20, P < 0.001) and substantially in mid-late pregnancy (β = −0.47, P < 0.001) compared with postpartum. Insulin secretory response (adjusted for insulin sensitivity) was augmented in early pregnancy (β = 0.16, P < 0.001) and mid-late pregnancy (β = 0.16, P = 0.001) compared with postpartum. Compared with postpartum, the PIP index was augmented in early pregnancy (β = 215, P = 0.04) but not mid-late pregnancy (β = 55, P = 0.64). Early GDM was distinguished by a substantial reduction in early pregnancy insulin sensitivity (β = −0.59, P < 0.001) compared with postpartum. Both early and classic GDM lacked evidence of early pregnancy augmentation of insulin secretory response (adjusted for insulin sensitivity) and the PIP index (P > 0.1 vs. postpartum). Early pregnancy PIP index predicted GDM independent of participant characteristics (area under the curve without PIP index 0.70 [95% CI 0.61–0.79], area under the curve with PIP index 0.87 [95% CI 0.80–0.93]).
β-Cell function is enhanced in early pregnancy. Deficient first-trimester β-cell function predicts GDM.
This article contains supplementary material online at https://doi.org/10.2337/figshare.22184218.