Clinical Trial ARTICLE
Reduced glycemic variability in diazoxide-responsive children with congenital hyperinsulinism using supplemental omega-3-polyunsaturated fatty acids; a pilot trial with MaxEPAR
- 1Department of Paediatric Endocrinology, Manchester Academic Health Science Centre, Royal Manchester Children’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
- 2Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
- 3Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
- 4School of Mathematics, University of Manchester, Manchester, UK
- 5Faculty of Life Sciences, University of Manchester, Manchester, UK
Objective: 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.
Design: Open label pilot trial with MaxEPAR 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).
Methods: 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).
Results: 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.
Conclusion: MaxEPAR 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.
Keywords: congenital hyperinsulinism, hypoglycemia, clinical trial, omega-3-polyunsaturated fatty acids, diazoxide
Citation: Skae M, Avatapalle HB, Banerjee I, Rigby L, Vail A, Foster P, Charalambous C, Bowden L, Padidela R, Patel L, Ehtisham S, Cosgrove KE, Dunne MJ and Clayton PE (2014) Reduced glycemic variability in diazoxide-responsive children with congenital hyperinsulinism using supplemental omega-3-polyunsaturated fatty acids; a pilot trial with MaxEPAR. Front. Endocrinol. 5:31. doi: 10.3389/fendo.2014.00031
Received: 16 December 2013; Paper pending published: 10 January 2014;
Accepted: 21 February 2014; Published online: 12 March 2014.
Edited by:Fabrizio Barbetti, University of Tor Vergata, Italy
Reviewed by:Arianna Maiorana, Bambino Gesù Children’s Hospital, Italy
Carlo Dionisi-Vici, Bambino Gesù Children’s Research Institute, Italy
Copyright: © 2014 Skae, Avatapalle, Banerjee, Rigby, Vail, Foster, Charalambous, Bowden, Padidela, Patel, Ehtisham, Cosgrove, Dunne and Clayton. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Indraneel Banerjee, Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Oxford Road, Manchester M13 9WL, UK e-mail: firstname.lastname@example.org; email@example.com