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Effects of treatment with metformin and/or sitagliptin on beta-cell function and insulin resistance in prediabetic women with previous gestational diabetes.
Diabetes, Obesity and Metabolism ( IF 5.4 ) Pub Date : 2019-12-04 , DOI: 10.1111/dom.13940
Giuseppe Daniele 1 , Andrea Tura 2 , Angela Dardano 1 , Alessandra Bertolotto 1 , Cristina Bianchi 1 , Laura Giusti 1 , Jancy Joseph Kurumthodathu 1 , Stefano Del Prato
Affiliation  

AIM To investigate the effect of sitagliptin (SITA) and metformin (MET) monotherapy as well as in combination (MET+SITA) on beta-cell function and insulin sensitivity in women with recent gestational diabetes (GDM) and impaired glucose regulation (IGR: impaired fasting glucose and/or impaired glucose tolerance). MATERIAL AND METHODS Forty women were randomly assigned to receive SITA (100 mg qd), MET (850 mg bid) or MET+SITA (50 + 850 mg bid) for 16 weeks. A 75 g oral glucose tolerance test (OGTT) and +125 mg/dL hyperglycaemic clamp followed by 5 g i.v. L-arginine were performed at baseline and end of study. The primary outcome of the study was the mean change in arginine-stimulated insulin secretion rate during the hyperglycaemic clamp test from baseline to 16-week therapy. RESULTS At week 16, body mass index declined in all groups (-1.2 ± 0.2 kg/m2 ; P < 0.05). MET+SITA gave a greater increase of first phase(2-10 min) insulin secretion and arginine-stimulated response (720.3 ± 299.0 to 995.5 ± 370.3 pmol/L and 3.2 ± 0.6 to 4.8 ± 1.0 pmoL/min, respectively, both P < 0.05) compared with MET and SITA. Similarly, MET+SITA was more effective in increasing OGTT-based glucose sensitivity (55.7 ± 11.3 to 108 ± 56.2 pmol x min-1 m-2 x mM-1 ; P = 0.04) and insulin-stimulated glucose disposal (M/I: 2.2 ± 0.5 to 4.6 ± 1.3 mg/kg/min÷μIU/min/ml; P = 0.04; Matsuda index [SI]: 3.1 ± 0.4 to 5.7 ± 1.1; P = 0.03) compared with either MET or SITA. Disposition index (ISSI-2) increased with MET+SITA and SITA (both P < 0.05), while no significant change was observed in MET. Among MET+SITA women, 33% reverted to normal glucose tolerance (NGT) compared with 14% with MET and 7% with SITA (P < 0.05). CONCLUSION This study shows that MET+SITA is superior to SITA and MET monotherapy regarding beta-cell function and insulin sensitivity improvement in IGR women with previous GDM, and may offer a potential pharmacologic intervention to reduce the risk of type 2 diabetes in this high-risk population.

中文翻译:

二甲双胍和/或西格列汀治疗对患有妊娠糖尿病的前驱糖尿病妇女的β细胞功能和胰岛素抵抗的影响。

目的 研究西格列汀 (SITA) 和二甲双胍 (MET) 单药治疗以及联合治疗 (MET+SITA) 对近期患有妊娠糖尿病 (GDM) 和血糖调节受损 (IGR:空腹血糖受损和/或糖耐量受损)。材料和方法 40 名女性被随机分配接受 SITA(100 mg qd)、MET(850 mg bid)或 MET+SITA(50 + 850 mg bid)治疗 16 周。在基线和研究结束时进行 75 g 口服葡萄糖耐量试验 (OGTT) 和 +125 mg/dL 高血糖钳夹,然后进行 5 g iv L-精氨酸。该研究的主要结果是从基线到 16 周治疗期间高血糖钳夹试验期间精氨酸刺激的胰岛素分泌率的平均变化。结果 在第 16 周,所有组的体重指数均下降 (-1.2 ± 0. 2公斤/平方米;P < 0.05)。MET+SITA 增加了第一阶段(2-10 分钟)胰岛素分泌和精氨酸刺激反应(分别为 720.3 ± 299.0 至 995.5 ± 370.3 pmol/L 和 3.2 ± 0.6 至 4.8 ± 1.0 pmol/min,均 P < 0.05) 与 MET 和 SITA 相比。类似地,MET+SITA 在增加基于 OGTT 的葡萄糖敏感性(55.7 ± 11.3 至 108 ± 56.2 pmol x min-1 m-2 x mM-1;P = 0.04)和胰岛素刺激的葡萄糖处理(M/I :2.2 ± 0.5 至 4.6 ± 1.3 mg/kg/min÷μIU/min/ml;P = 0.04;松田指数 [SI]:3.1 ± 0.4 至 5.7 ± 1.1;P = 0.03)与 MET 或 SITA 相比。处置指数(ISSI-2)随 MET+SITA 和 SITA 增加(均 P < 0.05),而 MET 未观察到显着变化。在 MET+SITA 女性中,33% 恢复正常葡萄糖耐量 (NGT),而 MET 和 SITA 分别为 14% 和 7% (P < 0. 05)。结风险人群。
更新日期:2019-12-27
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