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胰岛素自身免疫综合征在中国单一中心的诊断与治疗。

Insulin Autoimmune Syndrome Diagnosis and Therapy in a Single Chinese Center.

机构信息

Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

出版信息

Clin Ther. 2019 May;41(5):920-928. doi: 10.1016/j.clinthera.2019.03.009. Epub 2019 Apr 13.

Abstract

PURPOSE

Insulin autoimmune syndrome (IAS) is a relatively rare cause of hypoglycemia characterized by endogenous hyperinsulinism and autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. We present a series of IAS cases and describe the clinical characteristics of these cases.

METHODS

The medical records of inpatients with the final diagnosis of IAS were collected from August 2007 to August 2017 in Peking Union Medical College Hospital. Clinical characteristics and laboratory test results were summarized. The results of serum glucose, insulin, true insulin, and C-peptide testing during 5-h oral glucose tolerance tests were also summarized. Circulating immune complexes were assessed qualitatively by precipitation with polyethylene glycol (PEG) in some patients.

FINDINGS

Sixteen patients were included in this study. Insulin autoimmune antibody test results were found positive in 12 patients and weakly positive in 1 patient. Nine patients had an insulin to C-peptide molar ratio >1, whereas 6 patients had an insulin to C-peptide molar ratio <1. Circulating immune complexes were verified in all 4 patients who had been assessed with PEG. During 5-h oral glucose tolerance tests, the C-peptide level responded earlier to the glucose tolerance and had a shorter peak value period compared with insulin, although C-peptide's fluctuation still lagged behind the glucose fluctuation. Three patients presented with self-limited disease courses or limited disease course after discontinuing use of the sulfhydryl group drugs. Some patients' symptoms were relieved after small frequent meals, and some were relieved after taking acarbose. Only 3 patients took glucocorticoids as the anti-immune therapy.

IMPLICATIONS

The insulin to C-peptide molar ratios were not consistently >1 in patients with confirmed diagnoses of IAS in our study, which suggested the low sensitivity of insulin to C-peptide molar ratio to detect IAS. The therapy in our study also revealed the self-limited disease course of IAS, and despite the effectiveness of anti-immunity therapy, convenient therapy, such as frequent small meals and adding acarbose, performed well in many patients.

摘要

目的

胰岛素自身免疫综合征(IAS)是一种相对罕见的低血糖病因,其特征为内源性高胰岛素血症和针对内源性胰岛素的自身抗体,尽管患者此前并未接触过外源性胰岛素。我们报告一系列 IAS 病例,并描述这些病例的临床特征。

方法

我们收集了 2007 年 8 月至 2017 年 8 月期间在北京协和医院住院的最终诊断为 IAS 的患者的病历。总结了临床特征和实验室检查结果。还总结了 5 小时口服葡萄糖耐量试验期间血清葡萄糖、胰岛素、真胰岛素和 C 肽的检测结果。在一些患者中,通过聚乙二醇(PEG)沉淀定性评估循环免疫复合物。

结果

本研究纳入 16 例患者。12 例患者胰岛素自身抗体检测结果阳性,1 例患者弱阳性。9 例患者胰岛素与 C 肽摩尔比值>1,6 例患者胰岛素与 C 肽摩尔比值<1。所有 4 例接受 PEG 评估的患者均证实存在循环免疫复合物。在 5 小时口服葡萄糖耐量试验中,C 肽水平对葡萄糖耐量的反应早于胰岛素,且峰值期较短,尽管 C 肽的波动仍滞后于葡萄糖的波动。3 例患者疾病呈自限性或停用巯基药物后疾病呈局限性。一些患者症状在少食多餐后缓解,一些患者在服用阿卡波糖后缓解。仅 3 例患者接受糖皮质激素作为免疫治疗。

结论

在我们的研究中,经证实患有 IAS 的患者胰岛素与 C 肽摩尔比值并不始终>1,这提示胰岛素与 C 肽摩尔比值对 IAS 的检测敏感性较低。我们的治疗方法也揭示了 IAS 的自限性病程,尽管免疫治疗有效,但方便的治疗方法,如少食多餐和添加阿卡波糖,在许多患者中效果良好。

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