Exeter NIHR Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, U.K.
Diabetes Care. 2021 Jan;44(1):35-42. doi: 10.2337/dc20-1520. Epub 2020 Nov 12.
mutations cause neonatal diabetes mellitus that can be transient (TNDM) or, less commonly, permanent (PNDM); ∼90% of individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with PNDM require lower sulfonylurea doses and have milder neurological features than those with PNDM. However, these studies were short-term and included combinations of -PNDM and -TNDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated -PNDM.
We studied all 24 individuals with PNDM diagnosed in the U.K., Italy, France, and U.S. known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analyzed using nonparametric statistical methods.
Long-term data were obtained for 21 of 24 individuals (median follow-up 10.0 [range 4.1-13.2] years). Eighteen of 21 remained on sulfonylureas without insulin at the most recent follow-up. Glycemic control improved on sulfonylureas (presulfonylurea vs. 1-year posttransfer HbA 7.2% vs. 5.7%, = 0.0004) and remained excellent long-term (1-year vs. 10-year HbA 5.7% vs. 6.5%, = 0.04), = 16. Relatively high doses were used (1-year vs. 10-year dose 0.37 vs. 0.25 mg/kg/day glyburide, = 0.50) without any severe hypoglycemia. Neurological features were reported in 13 of 21 individuals; these improved following sulfonylurea transfer in 7 of 13. The most common features were learning difficulties (52%), developmental delay (48%), and attention deficit hyperactivity disorder (38%).
Sulfonylurea treatment of -PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.
突变导致新生儿糖尿病，可表现为一过性（TNDM）或更罕见的永久性（PNDM）；约 90%的患者可采用磺酰脲类药物治疗，而非胰岛素。既往研究表明，PNDM 患者需要的磺酰脲类药物剂量较低，且神经特征较 PNDM-TNDM 患者更为轻微。然而，这些研究时间较短，且纳入了 PNDM-TNDM 联合病例。我们旨在评估磺酰脲类药物治疗的 PNDM 患者的长期血糖和神经结局。
我们研究了在英国、意大利、法国和美国确诊为 PNDM 的 24 名患者，这些患者在 2010 年 5 月之前从胰岛素转为磺酰脲类药物治疗。采用非参数统计方法分析血糖控制、磺酰脲类药物剂量、低血糖等不良反应以及神经特征数据。
24 名患者中有 21 名（中位随访时间 10.0[范围 4.1-13.2]年）获得了长期数据。在最近一次随访中，21 名患者中有 18 名继续使用磺酰脲类药物而无需胰岛素。磺酰脲类药物治疗后血糖控制改善（磺酰脲类药物治疗前 vs. 1 年时的糖化血红蛋白 7.2% vs. 5.7%， = 0.0004），长期血糖控制仍良好（1 年时 vs. 10 年时的糖化血红蛋白 5.7% vs. 6.5%， = 0.04）， = 16。患者使用的磺酰脲类药物剂量相对较高（1 年时 vs. 10 年时的格列本脲剂量 0.37 vs. 0.25mg/kg/天， = 0.50），且无严重低血糖发生。21 名患者中有 13 名报告了神经特征；在这 13 名患者中，有 7 名在磺酰脲类药物转换后神经特征得到改善。最常见的特征是学习困难（52%）、发育迟缓（48%）和注意缺陷多动障碍（38%）。
磺酰脲类药物治疗 PNDM 可实现长期良好的血糖控制。PNDM 患者常出现明显的神经特征，且磺酰脲类药物治疗可能改善这些特征，支持早期、快速进行基因检测，以指导合理的治疗和神经发育评估。
