Asai Shiko, Ohta Akio, Kato Hiroyuki, Sada Yoshiyuki, Nagai Yoshio, Kondo Akihiko, Sasaoka Toshiyasu, Tanaka Yasushi
Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.
Endocr J. 2014;61(12):1213-20. doi: 10.1507/endocrj.EJ14-0194. Epub 2014 Sep 17.
We evaluated the effect of sitagliptin on glycemic control, endogenous insulin secretion, and beta cell function in Japanese patients with type 2 diabetes mellitus (T2DM) receiving a combination of oral antidiabetics and basal insulin analog glargine (basal-supported oral therapy [BOT]). Twenty-one patients showing inadequate glycemic control with BOT were given dipeptidylpeptidase-4 inhibitor (DPP-4I) sitagliptin at 50 mg/day for 12 weeks. Clinical markers of glycemic control, HbA1c, glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG), were measured before and 4 and 12 weeks after the start of sitagliptin. A 2-hour morning meal test was performed upon enrollment and at 12 weeks, and plasma glucose (PG), serum C-peptide, and plasma intact proinsulin (PI) were measured. HbA1c, GA, and 1,5-AG at 4 and 12 weeks were significantly improved over enrollment levels. The area under the PG concentration curve (AUC-PG) during the meal test at 12 weeks was significantly reduced (from 350 ± 17 mg ・ hr/dL before sitagliptin treatment to 338 ± 21 mg ・ hr/dL [mean ± SE], P < 0.05,); the AUC-C-peptide was unchanged (from 3.4 ± 0.4 ng ・ hr/mL to 3.6 ± 0.5 ng ・ hr/mL). However, both fasting and 2-hour PI/C-peptide ratios at 12 weeks were significantly decreased (from 13.3 ± 2.3 to 11.1 ± 2.0 [P < 0 .05] and from 9.5 ± 1.6 to 5.3 ± 0.9 [P < 0.01], respectively). Adding sitagliptin to BOT in Japanese T2DM patients appears to improve glycemic control without increasing endogenous insulin secretion and to reduce fasting and 2-hour postprandial PI/C-peptide ratios.
我们评估了西他列汀对接受口服降糖药与基础胰岛素类似物甘精胰岛素联合治疗(基础支持口服治疗[BOT])的日本2型糖尿病(T2DM)患者血糖控制、内源性胰岛素分泌及β细胞功能的影响。21例接受BOT治疗但血糖控制不佳的患者给予二肽基肽酶-4抑制剂(DPP-4I)西他列汀,剂量为50mg/天,持续12周。在开始使用西他列汀前、用药4周和12周后,测量血糖控制的临床指标糖化血红蛋白(HbA1c)、糖化白蛋白(GA)和1,5-脱水葡萄糖醇(1,5-AG)。入组时及12周时进行了2小时早餐试验,并测量了血浆葡萄糖(PG)、血清C肽和血浆完整胰岛素原(PI)。4周和12周时的HbA1c、GA和1,5-AG较入组时显著改善。12周时早餐试验期间的PG浓度曲线下面积(AUC-PG)显著降低(从西他列汀治疗前的350±17mg・hr/dL降至338±21mg・hr/dL[均值±标准误],P<0.05);AUC-C肽无变化(从3.4±0.4ng・hr/mL降至3.6±0.5ng・hr/mL)。然而,12周时空腹及餐后2小时的PI/C肽比值均显著降低(分别从13.3±2.3降至11.1±2.0[P<0.05]和从9.5±1.6降至5.3±0.9[P<0.01])。在日本T2DM患者的BOT治疗中添加西他列汀似乎可改善血糖控制,而不增加内源性胰岛素分泌,并降低空腹及餐后2小时的PI/C肽比值。