Hepatic Insulin Resistance Is an Early Determinant of Declining β-Cell Function in the First Year Postpartum After Glucose Intolerance in Pregnancy

OBJECTIVE: The increased risk of type 2 diabetes in women with glucose intolerance in pregnancy is mediated by deterioration of their β-cell function, which occurs as early as the first year postpartum. We thus sought to identify early determinants of their declining β-cell function. RESEARCH DESIGN AND METHODS: Women with recent gestational glucose intolerance (166) underwent oral glucose tolerance test at 3 and 12 months postpartum. They were stratified into those in whom β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]) declined over this time (decliners; n = 92) and those in whom it did not (nondecliners; n = 74). RESULTS: Between 3 and 12 months, hepatic insulin sensitivity (1/homeostasis model assessment of insulin resistance [HOMA-IR]) decreased in decliners but not in nondecliners. Over this time, the change in 1/HOMA-IR emerged as an independent predictor of the change in ISSI-2 (t = 5.5; P < 0.0001). Increased hepatic insulin sensitivity independently predicted a lower likelihood of declining β-cell function (odds ratio = 0.13 [95% CI 0.06–0.29]; P < 0.0001). CONCLUSIONS: Hepatic insulin resistance is an early determinant of declining β-cell function after gestational dysglycemia.