目的 探討硫辛酸致胰島素自身免疫綜合征(IAS)的臨床特點(diǎn),為臨床安全用藥提供依據(jù)。方法 檢索國(guó)內(nèi)外數(shù)據(jù)庫(kù)收集硫辛酸致IAS的病例報(bào)告類文獻(xiàn),提取相關(guān)數(shù)據(jù)(性別、國(guó)籍、年齡、原發(fā)疾病、聯(lián)用藥物、IAS發(fā)生時(shí)間及相關(guān)實(shí)驗(yàn)室檢查、主要癥狀、臨床干預(yù)措施及轉(zhuǎn)歸)進(jìn)行描述性統(tǒng)計(jì)分析,同時(shí)對(duì)相關(guān)廠家藥品說(shuō)明書進(jìn)行查閱分析。結(jié)果 納入分析的21例患者,男性4例,女性17例;年齡32~77歲,平均57.71歲;11例患者合并其他藥品,其中5例患者合并使用胰島素或胰島素促泌劑格列齊特,患者使用二甲雙胍或阿卡波糖為5例;4例患者在用藥過(guò)程中發(fā)生IAS,12例患者為停用硫辛酸后發(fā)生IAS;患者低血糖發(fā)作時(shí)血糖平均為2.46 mmol/L;21例患者血清胰島素均高于正常水平且胰島素自身抗體(IAA)均為陽(yáng)性。對(duì)14例患者進(jìn)行基因型檢測(cè),中國(guó)、日本和韓國(guó)患者基因型均為HLA-DRB1*0406,非東亞患者基因型分別為HLA-DRB1*0403或HLA-DRB1*0415。21例患者均停用硫辛酸,其中6例患者停藥后未干預(yù)患者好轉(zhuǎn),9例患者同時(shí)給予糖皮質(zhì)激素治療,1例患者給予二氮嗪,1例患者給予糖皮質(zhì)激素后仍未改善最終給予血漿置換治療,21例患者均好轉(zhuǎn)。結(jié)論 糖尿病患者使用硫辛酸時(shí)發(fā)生低血糖癥狀應(yīng)警惕硫辛酸所致IAS,臨床用藥過(guò)程中應(yīng)加強(qiáng)用藥監(jiān)護(hù),同時(shí)相關(guān)企業(yè)應(yīng)完善藥品說(shuō)明書,確保患者安全用藥。

Objective To explor the clinical characteristics of insulin autoimmune syndrome induced by lipoic acid.Methods Cases of insulin autoimmune syndrome caused by lipoic acid were collected and analyzed statistically in China and abroad, extracted literatures were analyzed statistically in respects of patient’s gender, nationality, age, primary disease, combined drugs, insulin autoimmune syndrome occurrence time, insulin autoimmune syndrome related laboratory examination, main symptoms, clinical intervention measures and outcome. At the same time, the drug instructions of four domestic manufacturers were consulted and analyzed.Results The 21 patients included in the analysis were 4 males and 17 females. The age ranged from 32 to 77 years, with an average of 57.71 years. 11 patients were combined with other drugs, of which 5 patients were combined with insulin or insulin secretagogue such as gliclazide, 5 patients were treated with metformin or acarbose. IAS occurred in 4 patients and 12 patients after stopping lipoic acid, the average blood glucose was 2.46 mmol/L at the onset of hypoglycemia. The serum insulin level of 21 patients was higher than normal, insulin autoantibody (IAA) was positive. Genotypes were detected in 14 patients, the genotypes of Chinese, Japanese and Korean patients were HLA-DRB1*0406, and those of non East Asian patients were HLA-DRB1*0403 or HLADRB1*0415. Lipoic acid was stopped in 21 patients, of which 6 patients did not interfere with the improvement after drug withdrawal, 9 patients were treated with glucocorticoid, 1 patient was treated with diazoxide, 1 patient was treated with glucocorticoid and did not improve, finally plasma exchange treatment was given, all patients were improved.Conclusion When lipoic acid is used to produce hypoglycemic symptoms, we should be alert to insulin autoimmune syndrome, strengthen medication monitoring in the process of clinical medication, and relevant enterprises should improve the drug instructions and ensure patients safety.

R977

陜西省重點(diǎn)研發(fā)計(jì)劃一般項(xiàng)目(2021SF-226);陜西省重點(diǎn)研發(fā)計(jì)劃一般項(xiàng)目(2020SF-062)