DISTINCT INSULIN PHYSIOLOGY TRAJECTORIES IN EUGLYCEMIC PREGNANCY AND GESTATIONAL DIABETES MELLITUS

Objective: To evaluate changes in insulin physiology in euglycemic pregnancy and gestational diabetes (GDM).

Research Design and Methods: Participants underwent oral glucose tolerance tests at ≤15 weeks’ gestation (early), 24-32 weeks’ gestation (mid-late), 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 beta-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 (β=-0.20, p<0.001) and substantially in mid-late pregnancy (β=-0.47, p<0.001) compared to postpartum. Insulin secretory response (adjusted for insulin sensitivity) was augmented in early (β=0.16, p<0.001) and mid-late (β=0.16, p=0.001) pregnancy compared to postpartum. Compared to postpartum, the PIP index was augmented in early (β=215, p=0.04) but not mid-late (β=55, p=0.64) pregnancy. Early GDM was distinguished by a substantial reduction in insulin sensitivity in early pregnancy (β=-0.59, p<0.001) compared to 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 versus postpartum). Early pregnancy PIP index predicted GDM, independent of participant characteristics (AUC without PIP: 0.70 95% CI [0.61-0.79], AUC with PIP: 0.87 [0.80-0.93]).

Conclusions: Beta-cell function is enhanced in early pregnancy. Deficient first trimester beta-cell function predicts GDM.