title: Hepatic insulin resistance is an early determinant of declining β-cell function in the first year postpartum after glucose intolerance in pregnancy.
abstract: 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.
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada. rretnakaran@mtsinai.on.ca
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: Chang
authors.initials: C
authors.lastname: Ye
authors.forename: Anthony J G
authors.initials: AJ
authors.lastname: Hanley
authors.forename: Philip W
authors.initials: PW
authors.lastname: Connelly
authors.forename: Mathew
authors.initials: M
authors.lastname: Sermer
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D016640:Diabetes, Gestational / Q000097:blood / Q000503:physiopathology*; D005260:Female; D018149:Glucose Intolerance / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D016015:Logistic Models; D008875:Middle Aged; D049590:Postpartum Period; D011237:Predictive Value of Tests; D011247:Pregnancy; D012307:Risk Factors; D013997:Time Factors
chemical_list: D001786:Blood Glucose