Role of glucagon-like peptide-1 analogue versus amylin as an adjuvant therapy in type 1 diabetes in a closed loop setting with ePID algorithm.
Role of glucagon-like peptide-1 analogue versus amylin as an adjuvant therapy in type 1 diabetes in a closed loop setting with ePID algorithm.
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DOI：
10.1177/1932296814542153
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发表时间：
2014-09-01
影响因子：
5
通讯作者：
Heptulla, Rubina A
中科院分区：
文献类型：
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作者：
Renukuntla, Venkat Sasidhar;Ramchandani, Neesha;Heptulla, Rubina A
尽管使用了人工胰腺，但由于反常的高胰高血糖素血症引起的餐后高血糖症是糖尿病治疗的主要挑战。我们假设普兰林肽或依塞那肽的连续治疗可通过胰高血糖素抑制来减轻餐后阶段的高血糖，从而优化闭环（CL）系统的功能。招募接受胰岛素泵治疗的1型糖尿病（T1 DM）受试者参加3次27小时住院治疗（间隔2-4周），并通过CL系统以随机顺序接受胰岛素给药，接受（1）单用胰岛素（对照）、（2）艾塞那肽2.5 g +胰岛素、（3）普兰林肽30 g +胰岛素。在午餐和晚餐前给予药物，这是一顿60克碳水化合物的标准餐。根据ePID算法通过Medtronic CL系统进行胰岛素输注，并通过Medtronic Sof-sensor进行连续皮下葡萄糖监测。10例受试者（年龄23 ± 1岁，HbA 1c为7.29 ± 0.3%（56 ± 1 mmol/mol），T1 DM持续时间为10.6 ± 2.0年）参加了3部分研究。与胰岛素单药治疗（P <0.03）和普兰林肽（P > 0.05）相比，艾塞那肽在减轻餐后高血糖方面明显更好。与普兰林肽相比，艾塞那肽对胰高血糖素的抑制具有统计学显著性（P <0.03）。胰岛素需要量随持续治疗而降低，但无统计学意义。在CL背景下，胰岛素单药治疗可导致T1 DM患者的餐后高血糖，艾塞那肽连续治疗可有效降低餐后高血糖，应视为T1 DM的连续治疗。
Postprandial hyperglycemia due to paradoxical hyperglucagonemia is a major challenge of diabetes treatment despite the use of the artificial pancreas. We postulated that adjunctive therapy with pramlintide or exenatide would attenuate hyperglycemia in the postprandial phase through glucagon suppression, thereby optimizing the functioning of the closed-loop (CL) system. Subjects with type 1 diabetes (T1DM) on insulin pump therapy were recruited to participate in a 27-hour hospitalized admission on 3 occasions (2-4 weeks apart) and placed on the insulin delivery via CL system in random order to receive (1) insulin alone (control), (2) exenatide 2.5 g + insulin, (3) pramlintide 30 g + insulin. Medications were given prior to lunch and dinner, which was a standardized meal of 60 grams of carbohydrates. Insulin delivery was as per the ePID algorithm via the Medtronic CL system and continuous subcutaneous glucose monitoring via Medtronic Sof-sensors. Ten subjects age 23 ± 1 years with a HbA1c of 7.29 ± 0.3% (56 ± 1 mmol/mol) and duration of T1DM 10.6 ± 2.0 years participated in the 3-part study. Exenatide was found to be significantly better in attenuating postprandial hyperglycemia as compared to insulin monotherapy (P < .03) and pramlintide (P > .05). Glucagon suppression was statistically significant with exenatide (P < .03) as compared to pramlintide. Insulin requirements were lower with adjunctive therapy, but statistically insignificant. Insulin monotherapy results in postprandial hyperglycemia in T1DM in the CL setting and adjunctive therapy with exenatide reduces postprandial hyperglycemia effectively and should be considered as adjunctive therapy in T1DM.