在KCNJ11和ABCC8突变导致的单基因糖尿病中,KATP通道功能受损,磺脲类药物改善长期血糖控制。尽管KATP通道在大脑中广泛表达,磺脲类药物对神经功能的影响差异很大。我们评估了已发表的关于磺酰脲类对神经系统特征的潜在影响的证据,尤其是癫痫,认知,运动功能和肌肉张力,视觉电机集成,与KCNJ11和ABCC8相关的新生儿发病糖尿病的儿童和成人的注意力缺陷。
我们对文献进行了系统回顾和荟萃分析(PROSPERO,CRD42021254782),包括个体患者数据,根据PRISMA的说法,使用RevMan软件。我们还对证据的等级进行了分级。
我们选择了776种出版物中的34种。对114例患者进行磺酰脲类(格列本脲)治疗前后的整体神经功能评估,总体风险差异(RD)为58%(95CI,43%-74%;I2=54%),年龄小于4岁的亚组为73%(95CI,32%-113%;I2=0%);证据水平中等和高,分别。癫痫的EEG研究显示,KCNJ11突变患者的RD为56%(95CI,23%-89%;I2=34%),有高质量的证据.对于张力减退和运动功能,RD为90%(95CI,69%-111%;I2=0%)和73%(95CI,35%-111%;I2=0%),分别,有高水平的证据.
格列本脲可显著改善因KCNJ11或ABCC8突变引起的新生儿糖尿病患者的神经系统异常。低张力是反应最好的症状。较早的治疗开始与更大的益处相关。
In monogenic diabetes due to KCNJ11 and ABCC8 mutations that impair KATP- channel function, sulfonylureas improve long-term glycemic control. Although KATP channels are extensively expressed in the brain, the effect of sulfonylureas on neurological function has varied widely. We evaluated published evidence about potential effects of sulfonylureas on neurological features, especially epilepsy, cognition, motor function and muscular tone, visuo-motor integration, and attention deficits in children and adults with KCNJ11 and ABCC8-related neonatal-onset diabetes mellitus.
We conducted a systematic
review and meta-analyses of the literature (PROSPERO, CRD42021254782), including individual-patient data, according to PRISMA, using RevMan software. We also graded the level of evidence.
We selected 34 of 776 publications. The evaluation of global neurological function before and after sulfonylurea (glibenclamide) treatment in 114 patients yielded a risk difference (RD) of 58% (95%CI, 43%-74%; I2 = 54%) overall and 73% (95%CI, 32%-113%; I2 = 0%) in the subgroup younger than 4 years; the level of evidence was moderate and high, respectively. EEG studies of epilepsy showed a RD of 56% (95%CI, 23%-89%; I2 = 34%) in patients with KCNJ11 mutations, with a high quality of evidence. For hypotonia and motor function, the RDs were 90% (95%CI, 69%-111%; I2 = 0%) and 73% (95%CI, 35%-111%; I2 = 0%), respectively, with a high level of evidence.
Glibenclamide significantly improved neurological abnormalities in patients with neonatal-onset diabetes due to KCNJ11 or ABCC8 mutations. Hypotonia was the symptom that responded best. Earlier treatment initiation was associated with greater benefits.