title: Marked decline in beta cell function during pregnancy leads to the development of glucose intolerance in Japanese women.
abstract: The aim of this study is to investigate glucose metabolism longitudinally during pregnancy to explore mechanisms underlying gestational diabetes mellitus (GDM). We reviewed a total of 62 pregnant Japanese women who underwent a 75g oral glucose tolerance test (OGTT) twice during pregnancy (median: early, 13; late, 28 weeks' gestation) because of positive GDM screening. All showed normal OGTT results in early pregnancy. Based on late OGTT, 15 had GDM (late-onset GDM) and 47 normal glucose tolerance (NGT). In early pregnancy, there were no significant differences in insulin sensitivity (insulin sensitivity index derived from OGTT [IS(OGTT)] and homeostasis model assessment for insulin resistance [HOMA-IR]) and insulin secretion (a ratio of the total area-under-the-insulin-curve to the total area-under-the-glucose-curve [AUC(ins/glu)] and insulinogenic index [IGI]) between the NGT and late-onset GDM groups. In each group, insulin sensitivity significantly decreased from early to late pregnancy, most in the late-onset GDM group (each p < 0.05). The insulin secretion showed no significant changes with advancing pregnancy in both of the groups, although late-onset GDM showed significantly lower IGI compared with NGT in late OGTT (p < 0.05). When assessed beta cell function by OGTT-derived disposition index (i.e. Insulin Secretion-Sensitivity Index-2 and IGI/fasting insulin), the indices significantly decreased from early to late pregnancy in the both groups (each p < 0.05). Women with late-onset GDM showed significantly lower indices compared with NGT (each p < 0.05). The failure of beta cell to compensate for decreased insulin sensitivity could contribute to the development of the late-onset GDM.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Saisho
authors.forename: Kei
authors.initials: K
authors.lastname: Miyakoshi
authors.forename: Satoru
authors.initials: S
authors.lastname: Ikenoue
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kasuga
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Minegishi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000328:Adult; D015331:Cohort Studies; D016640:Diabetes, Gestational / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007564:Japan / Q000453:epidemiology; D008137:Longitudinal Studies; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007328:Insulin