Distinct Insulin Physiology Trajectories in Euglycemic Pregnancy and Gestational Diabetes Mellitus

OBJECTIVE To evaluate changes in insulin physiology in euglycemic pregnancy and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS 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. RESULTS 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]). CONCLUSIONS β-Cell function is enhanced in early pregnancy. Deficient first-trimester β-cell function predicts GDM.