Underland Lisa J, Ilkowitz Jeniece Trast, Katikaneni Ranjitha, Dowd Amy, Heptulla Rubina A
1 Department of Pediatrics, Division of Endocrinology and Diabetes, Children's Hospital at Montefiore, Bronx, NY, USA.
2 Department of Pediatrics, Division of Diabetes, NYU Lagone Medical Center, New York, NY USA.
J Diabetes Sci Technol. 2017 May;11(3):602-610. doi: 10.1177/1932296817699847. Epub 2017 Mar 28.
Postprandial hyperglycemia poses a challenge to closed-loop systems. Dipeptidyl peptidase-4 (DPP-4) inhibitors, like sitagliptin, reduce postprandial glucose concentrations in patients with type 2 diabetes. The objective of this study was to assess sitagliptin's role in type 1 diabetes (T1DM) as an adjunct therapy in reducing postprandial blood glucose with an insulin-only closed-loop system.
This was a randomized, double-blinded, placebo controlled, crossover design trial. The participants were18-35 years old, had T1DM, and an HbA1c of ≤ 8.5%. A dose determination study included eight subjects with T1DM. There were three study visits. Four hours after receiving study drug (placebo, sitagliptin 50 mg, sitagliptin 100 mg), subjects underwent a mixed meal tolerance test with assessment of hormone concentrations. In a second study, 15 subjects underwent two visits receiving either placebo or 100 mg of sitagliptin plus an insulin only closed-loop system for 25 hours with timed meals. Blood glucose and other hormone concentrations were analyzed using repeated measures ANOVA.
For the dose determination study, sitagliptin 100 mg resulted in reduced postprandial blood glucose ( P = .006). For the closed-loop study, glucose concentrations were lower in the treatment group, most prominently during the first two study meals ( P = .03). There was no difference in glucagon concentrations, but insulin concentrations and insulin delivery were lower in the treatment group.
Sitagliptin may be considered as an adjunct therapy in a closed-loop setting. Larger studies are needed to determine the role of oral agents like sitagliptin to lower postprandial hyperglycemia with closed loop.
餐后高血糖对闭环系统构成挑战。二肽基肽酶-4（DPP-4）抑制剂，如西他列汀，可降低2型糖尿病患者的餐后血糖浓度。本研究的目的是评估西他列汀在1型糖尿病（T1DM）中作为辅助治疗手段，联合仅使用胰岛素的闭环系统降低餐后血糖的作用。
这是一项随机、双盲、安慰剂对照的交叉设计试验。参与者年龄在18至35岁之间，患有T1DM，糖化血红蛋白（HbA1c）≤8.5%。剂量确定研究纳入了8名T1DM患者。共进行了三次研究访视。在接受研究药物（安慰剂、50毫克西他列汀、100毫克西他列汀）4小时后，受试者接受混合餐耐量试验，并评估激素浓度。在第二项研究中，15名受试者接受了两次访视，分别接受安慰剂或100毫克西他列汀加仅使用胰岛素的闭环系统，并定时进餐25小时。使用重复测量方差分析对血糖和其他激素浓度进行分析。
在剂量确定研究中，100毫克西他列汀可降低餐后血糖（P = 0.006）。在闭环研究中，治疗组的血糖浓度较低，在前两餐期间最为明显（P = 0.03）。胰高血糖素浓度无差异，但治疗组的胰岛素浓度和胰岛素输注量较低。
西他列汀可被视为闭环环境下的辅助治疗手段。需要开展更大规模的研究来确定西他列汀等口服药物在闭环情况下降低餐后高血糖的作用。
