AUTHOR=Skae Mars , Avatapalle Hima Bindu , Banerjee Indraneel (Indi) , Rigby Lindsey , Vail Andy , Foster Peter , Charalambous Christiana , Bowden Louise , Padidela Raja , Patel Leena , Ehtisham Sarah , Cosgrove Karen E., Dunne Mark , Clayton Peter 

TITLE=Reduced Glycemic Variability in Diazoxide-Responsive Children with Congenital Hyperinsulinism Using Supplemental Omega-3-Polyunsaturated Fatty Acids; A Pilot Trial with MaxEPAR

JOURNAL=Frontiers in Endocrinology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2014.00031

DOI=10.3389/fendo.2014.00031

ISSN=1664-2392

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Design:</bold> Open label pilot trial with MaxEPA<sup>R</sup> liquid (eicosapentaenoic and docosahexaenoic acid) PUFA (3 ml/day for 21 days) in diazoxide-responsive CHI patients (<uri xlink:href="https://eudract.ema.europa.eu/" xmlns:xlink="http://www.w3.org/1999/xlink">https://eudract.ema.europa.eu/</uri>, EudraCT number 201100363333).</p><p><bold>Methods:</bold> 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 &lt;4 and &gt;10 mmol/l, and safety of PUFA. All children were analyzed either as intention to treat (<italic>n</italic> = 13) or as per protocol (<italic>n</italic> = 7).</p><p><bold>Results:</bold> 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 (<italic>n</italic> = 7). The frequency of CGMS &lt;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 &gt;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.</p><p><bold>Conclusion:</bold> MaxEPA<sup>R</sup> 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.</p>