Warncke Katharina, Eckert Alexander, Kapellen Thomas, Kummer Sebastian, Raile Klemens, Dunstheimer Desiree, Grulich-Henn Jürgen, Woelfle Joachim, Wenzel Sandra, Hofer Sabine E, Dost Axel, Holl Reinhard W
Department of Pediatrics, Kinderklinik München Schwabing, Technical University of Munich School of Medicine, Munich, Germany.
Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany.
Pediatr Diabetes. 2022 Nov;23(7):999-1008. doi: 10.1111/pedi.13390. Epub 2022 Jul 23.
To describe clinical presentation/longterm outcomes of patients with ABCC8/KCNJ11 variants in a large cohort of patients with diabetes.
We analyzed patients in the Diabetes Prospective Follow-up (DPV) registry with diabetes and pathogenic variants in the ABCC8/KCNJ11 genes. For patients with available data at three specific time-points-classification as K -channel variant, 2-year follow-up and most recent visit-the longitudinal course was evaluated in addition to the cross-sectional examination.
We identified 93 cases with ABCC8 (n = 54)/KCNJ11 (n = 39) variants, 63 of them with neonatal diabetes. For 22 patients, follow-up data were available. Of these, 19 were treated with insulin at diagnosis, and the majority of patients was switched to sulfonylurea thereafter. However, insulin was still administered in six patients at the most recent visit. Patients were in good metabolic control with a median (IQR) A1c level of 6.0% (5.5-6.7), that is, 42.1 (36.6-49.7) mmol/mol after 2 years and 6.7% (6.0-8.0), that is, 49.7 (42.1-63.9) mmol/mol at the most recent visit. Five patients were temporarily without medication for a median (IQR) time of 4.0 (3.5-4.4) years, while two other patients continue to be off medication at the last follow-up.
ABCC8/KCNJ11 variants should be suspected in children diagnosed with diabetes below the age of 6 months, as a high percentage can be switched from insulin to oral antidiabetic drugs. Thirty patients with diabetes due to pathogenic variants of ABCC8 or KCNJ11 were diagnosed beyond the neonatal period. Patients maintain good metabolic control even after a diabetes duration of up to 11 years.
描述一大群糖尿病患者中携带ABCC8/KCNJ11基因变异患者的临床表现/长期预后。
我们分析了糖尿病前瞻性随访（DPV）登记处中患有糖尿病且ABCC8/KCNJ11基因存在致病变异的患者。对于在三个特定时间点有可用数据的患者——分类为钾通道变异、2年随访和最近一次就诊——除横断面检查外，还评估了其纵向病程。
我们鉴定出93例携带ABCC8（n = 54）/KCNJ11（n = 39）基因变异的患者，其中63例患有新生儿糖尿病。有22例患者有随访数据。其中，19例在诊断时接受胰岛素治疗，此后大多数患者改用磺脲类药物。然而，在最近一次就诊时仍有6例患者使用胰岛素。患者代谢控制良好，糖化血红蛋白（A1c）水平中位数（四分位间距）为6.0%（5.5 - 6.7），即2年后为42.1（36.6 - 49.7）mmol/mol，最近一次就诊时为6.7%（6.0 - 8.0），即49.7（42.1 - 63.9）mmol/mol。5例患者曾有中位（四分位间距）4.0（3.5 - 4.4）年的时间未用药，而另外2例患者在最后一次随访时仍未用药。
对于6个月以下诊断为糖尿病的儿童，应怀疑存在ABCC8/KCNJ11基因变异，因为其中很大一部分患者可以从胰岛素治疗转换为口服降糖药。30例因ABCC8或KCNJ11基因致病变异导致糖尿病的患者在新生儿期后被诊断。即使糖尿病病程长达11年，患者仍能保持良好的代谢控制。
