Dastamani Antonia, Güemes Maria, Walker Joanna, Shah Pratik, Hussain Khalid
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J Pediatr Endocrinol Metab. 2017 Oct 26;30(11):1219-1222. doi: 10.1515/jpem-2017-0148.
Sirolimus (mTOR inhibitor) is proven to be effective in children with congenital hyperinsulinism (CHI). Studies in animals suggest that sirolimus may have diabetogenic actions. However, its role in precipitating diabetes mellitus (DM) in children with CHI has not been reported.
A 16-year-old female with CHI due to a dominant ABCC8 gene mutation was switched from diazoxide therapy to sirolimus, due to the hypertrichosis side effect of diazoxide. She developed facial cellulitis that was treated with clarithromycin and a month later, once the infection was resolved, she was found to have persistent hyperglycaemia, and was diagnosed with DM. She was unresponsive to oral sulfonylurea therapy and is currently managed with metformin. Her mother, who had the same ABCC8 mutation, developed DM at her 30s.
Patients with dominant ABCC8 gene mutations are prone to DM in adulthood, but Sirolimus therapy might increase the risk of developing diabetes at an early age, as this case illustrates.
西罗莫司（一种mTOR抑制剂）已被证明对先天性高胰岛素血症（CHI）患儿有效。动物研究表明西罗莫司可能具有致糖尿病作用。然而，其在CHI患儿中引发糖尿病（DM）的作用尚未见报道。
一名16岁女性因显性ABCC8基因突变患有CHI，由于二氮嗪的多毛副作用，从二氮嗪治疗改为西罗莫司治疗。她发生了面部蜂窝织炎，接受了克拉霉素治疗，一个月后，感染消退后，发现她持续存在高血糖，并被诊断为DM。她对口服磺脲类药物治疗无反应，目前用二甲双胍治疗。她的母亲也有相同的ABCC8突变，在30多岁时患了DM。
如本病例所示，具有显性ABCC8基因突变的患者成年后易患DM，但西罗莫司治疗可能会增加早年患糖尿病的风险。
