title: Disproportionately Elevated Proinsulin Levels as an Early Indicator ofβ-Cell Dysfunction in Nondiabetic Offspring of Chinese Diabetic Patients.
abstract: Objective.To study the characteristics ofβ-cell dysfunction and insulin resistance (IR) in the first-degree relatives (FDRs) of T2DM in Chinese population and to examine the usefulness of proinsulin (PI) for evaluatingβ-cell dysfunction.Methods. 229 subjects of nondiabetic FDRs, 71 newly diagnosed T2DM, and 114 with normal glucose tolerance (NGT) but not FDRs (NGT-non-FDRs) were verified by a 2-hour oral glucose tolerance test. Specific insulin (SI) and PI were measured by highly sensitive ELISA.Results. Compared to NGT-non-FDRs, NGT-FDRs showed higher levels of fasting and 2-hour PI, fasting PI-to-SI ratio (FPI/SI), and HOMA-IR (p< 0.01). Meanwhile, fasting PI, FPI/SI, and HOMA-IR were increased steadily from NGT-FDRs to prediabetes-FDRs and were highest in T2DM group (p< 0.001), whereas a significant decrease in HOMA-B could be observed only in T2DM group. Moreover, a progressive deterioration ofβ-cell function in NGT-FDRs, prediabetes-FDRs, and T2DM could be identified by FPI/SI even after adjusting for HOMA-IR: relative to non-FDRs controls, mean FPI/SI levels were increased 1.5, 2.0, and 4.7-fold, respectively (allp< 0.01).Conclusions.β-cell dysfunction as assessed by disproportionate secretion of proinsulin and IR by HOMA (using specific insulin assay) already exist in FDRs of T2DM even with normal glucose status. Compared with HOMA-B, FPI/SI could detectβ-cell failure in earlier stage of diabetes development.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Ming
authors.identifier: 0000-0002-8427-605X
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, 5 Jingyuanlu, Beijing 100043, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, 5 Jingyuanlu, Beijing 100043, China.
authors.forename: Shan
authors.identifier: 0000-0001-9291-2442
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, PLA General Hospital, Beijing 100853, China.
authors.forename: Juming
authors.initials: J
authors.lastname: Lu