Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, People's Republic of China.
IUBMB Life. 2017 Sep;69(9):756-766. doi: 10.1002/iub.1657. Epub 2017 Jul 31.
β-Cell dedifferentiation, characterized by loss of glucose sensitivity (β-cell glucose sensitivity [βCGS]), has been reported to play an important role in the development of type 2 diabetes (T2D). Traditionally, βCGS was derived from C-peptide-based method. However, C-peptide was not routinely examined in normal subjects and diabetes never treated with insulin. Thus, the aim of the study was to evaluate the use of insulin in oral glucose tolerance test (OGTT) in estimation of β-cell glucose response ability. A total of 1,599 subjects including normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and T2D were included in the study. A subgroup of NGT subjects (n = 591) were followed up for an average duration of 56.88 ± 20.76 months. Insulin release rate (IRR ) in the function of glucose (IRR response to glucose [IRRG]) during OGTT was compared with βCGS. Both βCGS derived from C-peptide by deconvolution approach and IRRG by insulin release progressively declined from NGT to IGT and T2D. Both βCGS and IRRG were associated with deposit of first-phase insulin secretion (DI ). After 56.88 ± 20.76 months, 32 (5.41%) NGT subjects had developed T2D. NGT subjects who progressed to diabetes after follow-up had lower IRRG and DI levels than those who did not (P < 0.01). Furthermore, multiple logistic regression analyses showed that decreased IRRG was a significant independent risk predictor for future diabetes after adjustment of age, body mass index (BMI), homeostasis model assessment (HOMA)-insulin resistance, DI and family history. NGT subjects with decreased IRRG during OGTT had defective early insulin secretion and were at higher risk of developing diabetes. IRRG could be a useful T2D predictor in NGT subjects. © 2017 IUBMB Life, 69(9):756-766, 2017.
β 细胞去分化，其特征是葡萄糖敏感性丧失（β 细胞葡萄糖敏感性[βCGS]），据报道在 2 型糖尿病（T2D）的发展中起重要作用。传统上，βCGS 源自基于 C 肽的方法。然而，C 肽在正常受试者中未常规检查，也从未在从未接受胰岛素治疗的糖尿病患者中检查。因此，本研究旨在评估口服葡萄糖耐量试验（OGTT）中胰岛素的使用在估计β细胞葡萄糖反应能力中的作用。共有 1599 名受试者，包括正常糖耐量（NGT）、糖耐量受损（IGT）和 T2D，包括在该研究中。NGT 受试者的亚组（n=591）平均随访 56.88±20.76 个月。OGTT 中葡萄糖的胰岛素释放率（IRR）（IRR 对葡萄糖的反应[IRRG]）与βCGS 进行了比较。从 NGT 到 IGT 和 T2D，βCGS 和 IRRG 均呈递减趋势。βCGS 和 IRRG 均与第一时相胰岛素分泌的沉积（DI）有关。56.88±20.76 个月后，32 名（5.41%）NGT 受试者发展为 T2D。随访后进展为糖尿病的 NGT 受试者的 IRRG 和 DI 水平低于未进展为糖尿病的 NGT 受试者（P<0.01）。此外，多元逻辑回归分析表明，在调整年龄、体重指数（BMI）、稳态模型评估（HOMA）-胰岛素抵抗、DI 和家族史后，IRRG 降低是未来发生糖尿病的显著独立危险因素。OGTT 期间 IRRG 降低的 NGT 受试者早期胰岛素分泌功能受损，发生糖尿病的风险更高。IRRG 可能是 NGT 受试者中有用的 T2D 预测指标。
