Pediatric Gynecology Diabetes and Endocrinology, APHP Centre - Hôpital Universitaire Necker Enfants Malades, Paris, France.
Faculty of Medicine, Institute of Maternal and Child Research (IDIMI), University of Chile, Santiago, Chile.
Pediatr Diabetes. 2020 Sep;21(6):932-941. doi: 10.1111/pedi.13041. Epub 2020 Jul 20.
A precision medicine approach is used to improve treatment of patients with monogenic diabetes. Herein, we searched SU efficiency according to the genotype-phenotype correlation, dosage used, and side effects.
Systematic review conducted according the PRISMA control criteria identifying relevant studies evaluating the in vivo and in vitro sensitivity of ATP-dependent potassium channels according to the characteristics of genetic mutation.
Hundred and three selected articles with complete data in 502 cases in whom 413 (82.3%) had mutations in KCNJ11 (#64) and 89 in ABCC8 (# 56). Successful transfer from insulin to SU was achieved in 91% and 86.5% patients, respectively, at a mean age of 36.5 months (0-63 years). Among patients with KCNJ11 and ABCC8 mutations 64 and 46 were associated with constant success, 5 and 5 to constant failure, and 10 and 4 to variable degrees of reported success rate, respectively. The glibenclamide dosage required for each genotype ranged from 0.017 to 2.8 mg/kg/day. Comparing both the in vivo and in vitro susceptibility results, some mutations appear more sensitive than others to sulfonylurea treatment. Side effects were reported in 17/103 of the included articles: mild gastrointestinal symptoms and hypoglycaemia were the most common. One premature patient had an ulcerative necrotizing enterocolitis which association with SU is difficult to ascertain.
Sulfonylureas are an effective treatment for monogenic diabetes due to KCNJ11 and ABCC8 genes mutations. The success of the treatment is conditioned by differences in pharmacogenetics, younger age, pharmacokinetics, compliance, and maximal dose used.
采用精准医学方法改善单基因糖尿病患者的治疗效果。在此，我们根据基因型-表型相关性、使用剂量和副作用来寻找 SU 的疗效。
根据 PRISMA 对照标准进行系统评价，确定了评估根据基因突变特征的 ATP 依赖性钾通道体内和体外敏感性的相关研究。
在 502 例具有完整数据的患者中，有 103 篇文章被选中，其中 413 例（82.3%）有 KCNJ11（#64）突变，89 例有 ABCC8（#56）突变。分别有 91%和 86.5%的患者在平均年龄为 36.5 个月（0-63 岁）时成功从胰岛素转为 SU。在 KCNJ11 和 ABCC8 突变患者中，64 例和 46 例与持续成功相关，5 例和 5 例与持续失败相关，10 例和 4 例与报告的成功率不同程度相关。每种基因型所需的格列本脲剂量范围为 0.017 至 2.8 mg/kg/天。比较体内和体外的敏感性结果，一些突变对磺酰脲类药物治疗的敏感性似乎高于其他突变。在纳入的 103 篇文章中有 17 篇报道了副作用：最常见的是轻微的胃肠道症状和低血糖。一名早产患者患有溃疡性坏死性小肠结肠炎，其与 SU 的关系难以确定。
磺酰脲类药物是治疗 KCNJ11 和 ABCC8 基因突变引起的单基因糖尿病的有效方法。治疗的成功取决于药物遗传学、年龄较小、药代动力学、依从性和使用的最大剂量等方面的差异。
