Enhancement of postprandial endogenous insulin secretion rather than exogenous insulin injection ameliorated insulin antibody-induced unstable diabetes: a case report
Enhancement of postprandial endogenous insulin secretion rather than exogenous insulin injection ameliorated insulin antibody-induced unstable diabetes: a case report
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DOI：
10.1186/s12902-018-0326-3
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发表时间：
2019-01-08
影响因子：
2.7
通讯作者：
Katagiri, Hideki
中科院分区：
文献类型：
--
作者：
Kaneko, Keizo;Satake, Chihiro;Katagiri, Hideki
背景胰岛素注射，尤其是胰岛素类似物，偶尔会诱导产生具有高结合能力和低亲和力的胰岛素抗体，类似于胰岛素自身免疫综合征（IAS）的胰岛素自身抗体特征。这些类IAS胰岛素抗体的产生导致明显的血糖波动，伴有餐后高血糖和空腹低血糖。病例介绍一名有27年糖尿病史的66岁男性因明显的血糖波动入院。 56 岁时开始接受人胰岛素治疗，5 年后每天多次注射胰岛素类似物。经过第一年的胰岛素类似物治疗后，患者开始频繁出现早晨低血糖发作和日间高血糖。明显的高胰岛素血症（4500 U/mL）和具有高结合能力和低亲和力的高滴度胰岛素抗体（80.4%）表明IAS样胰岛素抗体正在引起严重的血糖波动。改变胰岛素配方（门冬胰岛素、常规人胰岛素、赖脯胰岛素）被证明是无效的。经过多次治疗试验，停止外源性胰岛素并在利拉鲁肽和伏格列波糖中添加米格列奈，最终减弱了血糖波动，增加了餐后胰岛素分泌。连续血糖监测显示早晨低血糖和餐后高血糖有所改善，血糖波动的平均幅度较小。因此，与外源注射胰岛素相比，内源性分泌的胰岛素直接、快速地作用于肝细胞，抑制餐后葡萄糖输出。结论：适当增强餐后内源性胰岛素，旨在抑制餐后葡萄糖输出，同时又不刺激外周过度葡萄糖摄取，可能有助于胰岛素治疗糖尿病。 抗体引起的血糖不稳定。
BackgroundInsulin injection, especially with insulin analogs, occasionally induces the production of insulin antibodies with high binding capacity and low affinity, similar to the insulin autoantibodies characteristic of insulin autoimmune syndrome (IAS). Production of these IAS-like insulin antibodies causes marked glycemic fluctuations with postprandial hyperglycemia and fasting hypoglycemia.Case presentationA 66-year-old man with a 27-year history of diabetes was admitted because of marked glycemic fluctuations. Human insulin treatment had been initiated at age 56, followed by multiple daily injections of insulin analogs 5years later. After the initial year of insulin analog treatment, the patient began to experience frequent morning hypoglycemic attacks and day-time hyperglycemia. Marked hyperinsulinemia (4500 U/mL) and high titers of insulin antibodies (80.4%) with high binding capacity and low affinity indicated that IAS-like insulin antibodies were causing severe glucose fluctuations. Altering insulin formulations (insulin aspart regular human insulin insulin lispro) proved to be ineffective. After several therapeutic trials, cessation of exogenous insulin and addition of mitiglinide to liraglutide with voglibose finally attenuated glycemic fluctuations with increased postprandial insulin secretion. Continuous glucose monitoring revealed improvement of morning hypoglycemia and postprandial hyperglycemia with smaller mean amplitude of glycemic excursion. Therefore, compared to exogenously injected insulin, endogenously secreted insulin directly and rapidly acts on hepatocytes and suppresses postprandial glucose output.ConclusionsProper enhancement of postprandial endogenous insulin aimed at suppressing postprandial glucose output without stimulating excessive glucose uptake in the periphery is potentially useful for treating diabetes with insulin antibody-induced glycemic instability.