摘要目的:分析2型糖尿病应用外源性胰岛素治疗后合并胰岛素自身免疫综合征患者的临床特点。方法:纳入复旦大学附属中山医院内分泌科2017年9月至2019年3月符合外源性胰岛素相关胰岛素自身免疫综合征(EIAS)诊断的2型糖尿病住院患者106例，收集患者临床资料、体格检查和实验室结果。结果:106例患者中84例(79.24%)使用预混人胰岛素或预混胰岛素类似物，18例患者(16.98%)近期反复发生低血糖。精氨酸刺激试验显示胰岛素0 min基线值中位数73.40(23.07～146.75)μU/ml，胰岛素4 min/0 min比值中位数1.27(1.03～1.85)，平均值1.72±1.47，胰岛素0 min(μU/ml)/C肽0 min(ng/ml)比值44.60(14.92～87.93)，平均值81.92±130.93。以本院空腹胰岛素检测参考值2倍上限(49.8 μU/ml)为切点，将患者分为胰岛素蓄积组(胰岛素0 min基线值≥49.8 μU/ml)和胰岛素非蓄积组(胰岛素0 min基线值<49.8 μU/ml)。胰岛素蓄积组66例患者中14例(21.21%)发生低血糖，胰岛素非蓄积组40例患者中4例(10%)发生低血糖，胰岛素蓄积组的胰岛素4 min/0 min比值、胰岛素0 min/C肽0 min比值、血糖水平标准差(SDBG)及最大血糖波动幅度(LAGE)均显著高于胰岛素非蓄积组( P<0.05)。在胰岛素蓄积组66例患者中，36例予更换胰岛素剂型(胰岛素治疗组)，30例停用胰岛素改为口服降糖药(口服药治疗组)的方案治疗后，2组治疗后的SDBG和LAGE均较治疗前明显下降(均 P<0.05)。 结论:随着外源性胰岛素蓄积的加重，患者血糖波动明显增加，低血糖比例显著升高。胰岛素自身免疫综合征患者胰岛功能出现特征性改变，精氨酸刺激后，胰岛素分泌无明显峰值，呈现"高平"曲线，基线胰岛素/C肽比值水平显著升高。及时诊断和调整治疗方案后，EIAS患者预后良好。

abstractsObjective:To analyze the clinical features of type 2 diabetic patients with insulin autoimmune syndrome after treatment with exogenous insulin.Methods:A total of 106 patients with type 2 diabetes diagnosed with exogenous insulin-related insulin autoimmune syndrome (EIAS) were included from September 2017 to March 2019 in the Department of Endocrinology, Zhongshan Hospital, Fudan University. The clinical data, physical examination, and laboratory examination results of patients were collected.Results:Of the 106 patients, 84 (79.24%) used premixed human insulin or premixed insulin analogs, and 18 patients (16.98%) presented recurrent hypoglycemia. The arginine stimulation test showed that the median value of the baseline insulin was 73.40 (23.07-146.75) μU/ml, and the median ratio of 4 minute insulin to 0 minute insulin was 1.27 (1.03-1.85), with the mean of the ratio 1.72±1.47. The ratio of baseline insulin (μU/ml) to C-peptide (ng/ml) was 44.60 (14.92-87.93), with an average of 81.92±130.93. Taking the two-fold upper limit of fasting insulin reference value (49.8 μU/ml) as the cut-off point, the subjects were divided into insulin accumulation group (baseline insulin≥49.8 μU/ml) and insulin non-accumulation group (baseline insulin <49.8 μU/ml). Among the 66 patients in the insulin accumulation group, 14 patients had hypoglycemia (21.21%) and 4 patients in the insulin non-accumulation group presented hypoglycemia (10%). The ratio of 4 minute insulin to baseline insulin, ratio of baseline insulin to C-peptide, blood glucose level standard deviation (SDBG) and maximum blood glucose fluctuation amplitude (LAGE) in the insulin accumulation group were significantly higher than those in the insulin non-accumulation group (all P<0.05). Among 66 patients in the insulin accumulation group, 36 patients changed the type of insulin preparafion (insulin treatment group), 30 patients were changed from insulin to oral hypoglycemic agents (oral medication group). After treatment, both SDBG and LAGE in the two groups were significantly lower than before treatment ( P<0.05). Conclusions:With the aggravation of exogenous insulin accumulation, the fluctuation of blood glucose and the proportion of hypoglycemia were significantly increased. There was a characteristic change in islet function in patients with insulin autoimmune syndrome. After arginine stimulation, there was no significant peak of insulin secretion, showing a " high-level" curve. The baseline insulin/C-peptide ratio was significantly increased. The prognosis of EIAS patients is good after timely diagnosis and adjustment of treatment.