Department of Paediatric Endocrinology, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK.
Department of Paediatric Endocrinology, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK ; Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester , Manchester , UK.
Front Endocrinol (Lausanne). 2014 Mar 12;5:31. doi: 10.3389/fendo.2014.00031. eCollection 2014.
Congenital hyperinsulinism (CHI) is a rare condition of hypoglycemia where therapeutic options are limited and often complicated by side-effects. Omega-3-polyunsaturated fatty acids (PUFA), which can suppress cardiac myocyte electrical activity, may also reduce ion channel activity in insulin-secreting cells. PUFA supplements in combination with standard medical treatment may improve glucose profile and may reduce glycemic variability in diazoxide-responsive CHI.
Open label pilot trial with MaxEPA(R) liquid (eicosapentaenoic and docosahexaenoic acid) PUFA (3 ml/day for 21 days) in diazoxide-responsive CHI patients (https://eudract.ema.europa.eu/, EudraCT number 201100363333).
Glucose levels were monitored pre-treatment, end of treatment, and at follow-up by subcutaneous continuous glucose monitoring systems (CGMS) in 13 patients (7 girls) who received PUFA. Outcome measures were an improved glucose profile, reduced glycemic variability quantified by a reduction in the frequency of glucose levels <4 and >10 mmol/l, and safety of PUFA. All children were analyzed either as intention to treat (n = 13) or as per protocol (n = 7).
Mean (%) CGMS glucose levels increased by 0.1 mmol/l (2%) in intention to treat and by 0.4 mmol/l (8%) in per protocol analysis (n = 7). The frequency of CGMS <4 mmol/l was significantly less at the end of treatment than in the pre-treatment period [556 (7%) vs. 749 (10%)]. Similarly, the frequency of CGMS >10 mmol/l, was also less at the end of treatment [27 (0.3%) vs. 49 (0.7%)]. Except for one child with increased LDL cholesterol, all safety parameters were normal.
MaxEPA(R) was safe and reduced glycemic variability, but did not increase glucose profiles significantly in diazoxide-responsive CHI. The supplemental value of PUFA should be evaluated in a comprehensive clinical trial.
先天性高胰岛素血症（CHI）是一种罕见的低血糖症，治疗选择有限，且常因副作用而变得复杂。ω-3 多不饱和脂肪酸（PUFA）可抑制心肌细胞电活动，也可能降低胰岛素分泌细胞中的离子通道活性。PUFA 补充剂与标准药物治疗联合使用可能改善血糖谱，并可能降低对二氮嗪有反应的 CHI 的血糖变异性。
对 13 名（7 名女孩）对二氮嗪有反应的 CHI 患者（https://eudract.ema.europa.eu/，EudraCT 编号 201100363333）进行开放性标签试验，用 MaxEPA（二十碳五烯酸和二十二碳六烯酸）PUFA（每天 3 毫升，持续 21 天）治疗。
通过皮下连续血糖监测系统（CGMS）监测治疗前、治疗结束时和随访时的血糖水平。13 名患者接受了 PUFA 治疗，观察指标为改善血糖谱，通过降低血糖水平<4 和>10mmol/L 的频率来降低血糖变异性，以及 PUFA 的安全性。所有患儿均按意向治疗（n=13）或方案（n=7）进行分析。
在意向治疗和方案分析中，CGMS 葡萄糖水平平均（%）分别升高了 0.1mmol/L（2%）和 0.4mmol/L（8%）（n=7）。治疗结束时，CGMS<4mmol/L 的频率明显低于治疗前[556（7%）比 749（10%）]。同样，CGMS>10mmol/L 的频率也较低[27（0.3%）比 49（0.7%）]。除一名患儿 LDL 胆固醇升高外，所有安全性参数均正常。
MaxEPA（R）安全，降低血糖变异性，但对二氮嗪有反应的 CHI 患者的血糖谱无显著升高。PUFA 的附加价值应在全面的临床试验中进行评估。
