Perera Ishan, Jensen Brooke, Patel Hirenkumar, Garganta Melissa
Center for Simulation and Technology, Edward Via College of Osteopathic Medicine, Blacksburg, VA, United States.
Department of Pediatrics, Carilion Roanoke Memorial Hospital, Roanoke, VA, United States.
Front Pediatr. 2025 Apr 16;13:1456818. doi: 10.3389/fped.2025.1456818. eCollection 2025.
Neonatal diabetes mellitus (NDM) is a rare disease, the prevalence of which is 1 in 90,000-160,000 live births, with 31% of all preterm diagnoses linked to monogenic causes. NDM is differentiated into transient, permanent, and syndromic NDM. Furthermore, 40% of patients diagnosed with NDM are responsive to oral sulfonylureas (SUs) due to expressed mutations of the ABCC8 or KCNJ11 genes coding for adenosine triphosphate-sensitive potassium channel (KATP) subunits in pancreatic beta (β) cells. SUs bind to the sulfonylurea receptor 1 subunit, closing the KATP channel and increasing insulin secretion. Although SUs remain the mainstay of NDM treatment, these medications are traditionally only dosed and approved for hyperglycemic control in adults. Current treatment regimens suggest a high dose, 1 mg/kg/day, for patients with KCNJ11 neonatal diabetes.
Our male neonate was born at 27 weeks and 1,020 g via emergency cesarean section due to complete placenta previa and maternal hemorrhage following perinatal betamethasone administration. Neonatal resuscitation was required. During resuscitation, the patient was intubated and found to be hyperglycemic. He was subsequently started on Regular Humulin at 0.1 units/kg/dose subcutaneously (SQ) and increased to 0.2 units/kg/dose SQ before transfer to our facility on day of life (DOL) 19. In our neonatal intensive care unit, the patient was transitioned to an insulin drip due to difficulty obtaining and administering the appropriate, but minuscule, SQ insulin doses. Genetic testing was positive for a pathogenic variant c.679G>A (p.Glu227Lys) in KCNJ11; therefore, glyburide was started at 0.1 mg/kg/dose twice a day on DOL 54, resulting in euglycemia. Hyperglycemia recurred after an initial attempt to wean; however, a subsequent wean on DOL 70 was successful in maintaining euglycemia without insulin or glyburide for 48 h prior to discharge on DOL 78.
This case report describes the unique and complicated clinical course of a premature neonate with an initially undifferentiated class of NDM requiring a microdose-based approach, i.e., a fraction of a regular dose, to both insulin and SU-based management. This report offers a concise recount of the applied diagnostic and therapeutic procedures while suggesting a decision tree for future NDM management in neonates.
新生儿糖尿病（NDM）是一种罕见疾病，其发病率为每90,000 - 160,000例活产中有1例，所有早产诊断中有31%与单基因病因有关。NDM可分为短暂性、永久性和综合征性NDM。此外，40%被诊断为NDM的患者对口服磺脲类药物（SUs）有反应，这是由于胰腺β细胞中编码三磷酸腺苷敏感性钾通道（KATP）亚基的ABCC8或KCNJ11基因发生了表达突变。SUs与磺脲类受体1亚基结合，关闭KATP通道并增加胰岛素分泌。尽管SUs仍然是NDM治疗的主要药物，但这些药物传统上仅按剂量给药并被批准用于成人的血糖控制。目前的治疗方案建议，对于患有KCNJ11新生儿糖尿病的患者，采用高剂量，即1mg/kg/天。
我们的男婴因完全性前置胎盘和围产期给予倍他米松后产妇出血，于孕27周时通过急诊剖宫产出生，出生体重1020g。需要进行新生儿复苏。复苏过程中，患儿插管后发现血糖升高。随后在出生后第19天转至我院之前，开始皮下注射正规胰岛素，初始剂量为0.1单位/kg/剂量，后增至0.2单位/kg/剂量。在我们的新生儿重症监护病房，由于难以获取和给予合适但极小剂量的皮下胰岛素，患儿转为胰岛素静脉滴注。基因检测显示KCNJ11基因存在致病性变异c.679G>A（p.Glu227Lys）；因此，在出生后第54天开始给予格列本脲，剂量为0.1mg/kg/剂量，每日两次，血糖恢复正常。在最初尝试减量后血糖再次升高；然而，随后在出生后第70天的减量成功维持了血糖正常，在出生后第78天出院前48小时未使用胰岛素或格列本脲。
本病例报告描述了一名早产新生儿独特而复杂的临床过程，该患儿最初患有未分化类型的NDM，在胰岛素和基于SUs的治疗中都需要基于微剂量的方法，即常规剂量的一小部分。本报告简要叙述了所应用的诊断和治疗程序，同时为未来新生儿NDM的管理提出了一个决策树。
