Deficient Glucagon Response to Hypoglycemia During a Mixed Meal in Total Pancreatectomy/Islet Autotransplantation Recipients
Deficient Glucagon Response to Hypoglycemia During a Mixed Meal in Total Pancreatectomy/Islet Autotransplantation Recipients
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DOI：
10.1210/jc.2017-02182
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发表时间：
2018-04-01
影响因子：
5.8
通讯作者：
Robertson, R. Paul
中科院分区：
文献类型：
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作者：
Bogachus, Lindsey D.;Bellin, Melena D.;Robertson, R. Paul
背景：全胰腺切除术和肝内胰岛自体移植（TP/IAT）用于缓解慢性胰腺炎患者的剧烈腹痛、避免使用麻醉剂、维持胰岛功能并避免糖尿病。然而，许多 TP/IAT 接受者抱怨餐后低血糖。目的：本研究旨在发现这一问题的机制。设计：参与者食用三同位素混合餐。背景：这项研究在医院研究单位进行。参与者：我们研究了 10 名 TP/IAT 接受者和 10 名年龄和体重指数匹配的对照受试者。 10 名接受者中有 7 人有餐后低血糖史。干预措施：给参与者提供 [1-C-13] 标记的混合餐和两次示踪剂输注（[6,6-(2)H2]-和 [6-H-3]-葡萄糖）。主要结果指标：测定血糖动力学和调节激素浓度。结果：餐后，接受者的血糖峰值立即升高与对照受试者相比[266 +/- 20 mg/dL (14.8 +/- 1.1 mmol/L) vs 185 +/- 13 mg/dL (10.3 +/- 0.7 mmol/L)； P = 0.01]。然而，TP/IAT 接受者餐后 240 至 360 分钟之间的平均 Delta 葡萄糖显着低于对照受试者 (P, 0.05)；七名有低血糖史的接受者中有六人出现异常低的餐后 Delta 葡萄糖。尽管餐后血糖异常降低，TP/IAT 接受者的 Delta 胰高血糖素保持不变（240 至 360 分钟；P = 0.58）。放射性同位素研究表明，TP/IAT 接受者的进餐情况、葡萄糖消失和内源性葡萄糖产生与对照受试者没有差异。结论：最初的高血糖水平，随后出现低血糖且缺乏胰高血糖素反应，是导致 TP/IAT 后餐后低血糖的机制序列。
Context: Total pancreatectomy and intrahepatic islet autotransplantation (TP/IAT) is performed to alleviate severe abdominal pain, avoid narcotic use, maintain islet function, and avoid diabetes in patients with chronic pancreatitis. However, many TP/IAT recipients complain of postprandial hypoglycemia.Objective: This study was designed to discover the mechanisms of this problem.Design: Participants consumed a triple-isotope mixed meal.Setting: This study was performed in a hospital research unit.Participants: We studied 10 TP/IAT recipients and 10 age-and body mass index-matched control subjects. Seven of 10 recipients had a history of postprandial hypoglycemia.Interventions: Participants were given a [1-C-13]-labeled mixed meal and two tracer infusions ([6,6-(2)H2]-and [6-H-3]-glucose).Main Outcome Measures: Glucose kinetics and concentrations of regulatory hormones were determined.Results: Immediately after the meal, peak glucose was elevated in recipients compared with control subjects [266 +/- 20 mg/dL (14.8 +/- 1.1 mmol/L) vs 185 +/- 13 mg/dL (10.3 +/- 0.7 mmol/L); P = 0.01]. However, mean Delta glucose for TP/IAT recipients betweenminutes 240 and 360 postprandially was significantly lower than for control subjects (P, 0.05); six of the seven recipients with a history of hypoglycemia experienced abnormally low postprandial Delta glucose. Delta Glucagon remained unchanged (minutes 240 to 360; P = 0.58) in TP/IAT recipients despite abnormal decreases in postprandial glucose. Radioisotopic studies revealed that meal appearance, glucose disappearance, and endogenous glucose production in TP/IAT recipients were not different from control subjects.Conclusion: Initially high glucose levels followed by hypoglycemia with an absent glucagon response is a mechanistic sequence that contributes to postprandial hypoglycemia after TP/IAT.