Sufficient increment of sulfonylurea without reintroduction of insulin ameliorates pubertal deterioration of glycaemic control in KCNJ11 neonatal diabetes treated with long-term sulfonylurea
Sufficient increment of sulfonylurea without reintroduction of insulin ameliorates pubertal deterioration of glycaemic control in KCNJ11 neonatal diabetes treated with long-term sulfonylurea
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在不重新引入胰岛素的情况下充分增加磺酰脲类可改善长期磺酰脲类治疗的 KCNJ11 新生儿糖尿病的青春期血糖控制恶化
DOI：
10.1007/s00125-020-05182-9
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发表时间：
2020
期刊：
影响因子：
8.2
通讯作者：
Hiroshi Azuma
中科院分区：
文献类型：
--
作者：
Shigeru Suzuki;Tokuo Mukai;Takahide Kokumai;Akiko Furuya;Yusuke Tanahashi;Hiroshi Azuma
编辑：KCNJ11杂合激活突变是新生儿糖尿病(NDM)的主要原因。尽管KCNJ11 NDM患者通常在胰岛素依赖状态下出现高血糖，但他们中的大多数人可以从胰岛素治疗转向大剂量磺脲类药物[1]。磺脲类药物的每体重给药剂量可能会随着时间的推移而减少，因为大多数患者表现出更好的血糖控制[2]。然而，一些人表现出长期的磺脲类药物治疗失败，这需要在青春期或青春期重新注射胰岛素[3]。这些血糖控制恶化的患者在再次输入胰岛素时的每体重磺脲剂量低于从胰岛素转移时的每体重初始剂量，还没有证实进一步增加磺脲剂量是否能控制青春期病情恶化的个体的血糖水平。在这里，我们报告了一个KCNJ11 NDM的病例，在该病例中，格列本脲增加到每体重初始剂量可以改善血糖控制的青春期恶化。一名31天大的男婴出现发热，被诊断为糖尿病(血糖水平，38.0mmo1/L)和无法检测到的免疫反应胰岛素水平。在1岁时，KCNJ11分析发现R201H杂合子突变，这是导致KCNJ11 NDM最常见的突变[1，3]。他成功地从胰岛素(0.8U kg−1day−1)转为格列本脲(日本赛诺菲)治疗(0.97 mg kg−1d−1)，当时他的HbA1c水平在20个月龄时为84 mmoL/−(9.8%)。除了短暂的轻度腹泻，没有观察到格列本脲或严重低血糖的其他副作用。直到儿童早期，患者的HbA1c水平一直控制在约44 mmol/mol(6.2%)，格列本脲的剂量逐渐减少(图1)。然而，他的HbA1c水平在青春期逐渐升高，从10岁开始(睾丸体积，4毫升[4])。患者坚持糖尿病治疗；我们每月咨询他，询问他坚持治疗的情况，确认他没有剩余的未用药。在一段时间内，患者的BMI SD评分大约为0。在11岁零4个月时，他的糖化血红蛋白水平上升到60 mmoL/m ol(7.6%)，而仍然服用0.16 mg kg−1d−1格列本脲。因此，格列本脲在12岁零8个月龄时逐渐增加到0.37 mg kg−1d−1。尽管格列本脲用量增加，但他的HbA1c水平恶化至73 mmol/mol(8.8%)。在12岁9个月龄时，格列本脲剂量增加到0.98 mg·kg-1·−-1·−-1·d-1，连续5天。连续血糖监测系统测得的平均血糖水平由11.8±3.0μ/L(平均±SD)降至8.7±2.6μ/L，尿C-肽水平由41.8±17.0 mgg/d(3d平均±SD)上升至56.4±2.6 mmog/d。随之而来的是，他的HbA1c水平在4个月后下降到53 mmol/mol(7.0%)(图1)。即使服用大剂量格列本脲，也没有发生严重的低血糖。在13岁零7个月时，他的HbA1c水平停止下降。因此，为了进一步改善血糖，每日服用三剂50毫克米格列醇(日本三和河谷)与格列本脲联合使用。
To the Editor: Heterozygous activating mutations in KCNJ11 are the major cause of neonatal diabetes mellitus (NDM). Although patients with KCNJ11 NDM usually develop hyperglycaemia in an insulin-dependent state, most of them can transfer from insulin treatment to high-dose sulfonylurea [1]. The administered dose per body weight of sulfonylurea might be reduced over time because most patients show better glycaemic control [2]. However, some individuals show failure of long-term sulfonylurea treatment, which necessitates the reintroduction of insulin during adolescence or puberty [3]. The dose per body weight of sulfonylurea for these patients with worsened glycaemic control at the time of reintroduction of insulin was lower than the initial dose per body weight at the time of transferring from insulin, and it has not been verified whether further increment in sulfonylurea dose can control glucose levels in individuals with worsened condition during puberty. Here, we report a case of KCNJ11 NDM in which an increase in glibenclamide to the initial dose per body weight improved the pubertal deterioration of glycaemic control. A 31-day-old male infant who presented with fever was diagnosed with diabetes (blood glucose level, 38.0 mmol/l) and undetectable immunoreactive insulin levels. At 1 year of age, KCNJ11 analysis revealed a de novo R201H heterozygous mutation, which is the most common mutation that gives rise to KCNJ11 NDM [1, 3]. He was successfully transferred from insulin (0.8 U kg− 1 day− 1) to glibenclamide (Sanofi, Japan) treatment (0.97 mg kg− 1 day− 1) when his HbA1c level was 84 mmol/mol (9.8%) at 20 months of age. Besides transitory mild diarrhoea, no other side effects of glibenclamide or severe hypoglycaemia were observed. The patient’s HbA1c level was well controlled to about 44 mmol/mol (6.2%) until early childhood, and the glibenclamide dose was tapered (Fig. 1). However, his HbA1c level gradually increased during puberty, which started at 10 years of age (testicular volume, 4 ml [4]). The patient adhered to the diabetes treatment; we consulted him monthly and asked about adherence, confirming that he did not have unused medication left over. The patient’s BMI SD score had been approximately 0 over a period of time. At 11 years and 4 months of age, his HbA1c level increased to 60 mmol/mol (7.6%) while still on 0.16 mg kg− 1 day− 1 glibenclamide. Thus, glibenclamide was gradually increased to 0.37 mg kg− 1 day− 1 at 12 years and 8 months of age. Despite the increase in glibenclamide, his HbA1c level worsened to 73 mmol/mol (8.8%). At 12 years and 9 months of age, the glibenclamide dose was increased to 0.98 mg kg− 1 day− 1 over 5 days. Consequently, the average (mean) blood glucose levels measured with a continuous glucose monitoring system decreased from 11.8±3.0 mmol/l (average±SD) to 8.7±2.6 mmol/l and urinary C-peptide level increased from 41.8±17.0 μg/day (3 day average±SD) to 56.4±2.6 μg/day. Along with that, his HbA1c level decreased to 53 mmol/mol (7.0%) 4 months later (Fig. 1). Even on highdose glibenclamide, severe hypoglycaemia did not occur. At 13 years and 7 months of age, his HbA1c levels stopped decreasing. Therefore, three doses of 50 mg miglitol (Sanwakagaku, Japan) per day were prescribed in combination with glibenclamide in the hope of further improving glycaemic
影响因子：
7.7
作者：
Moran, A;Jacobs, DR;Sinaiko, AR
通讯作者：
Sinaiko, AR
磺脲类治疗的 KCNJ11 新生儿糖尿病中的低血糖：轻度至中度症状发作很少发生，但不涉及意识不清或癫痫发作
影响因子：
3.4
作者：
Monica S. Lanning;D. Carmody;Łukasz Szczerbiński;L. Letourneau;R. Naylor;S. Greeley
通讯作者：
S. Greeley