title: Reduced Glycemic Variability in Diazoxide-Responsive Children with Congenital Hyperinsulinism Using Supplemental Omega-3-Polyunsaturated Fatty Acids; A Pilot Trial with MaxEPA(R.).
abstract: 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.
  
  
  METHODS
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatric Endocrinology, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK.
authors.forename: Mars
authors.initials: M
authors.lastname: Skae
authors.affiliation: Department of Paediatric Endocrinology, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK.
authors.forename: Hima Bindu
authors.initials: HB
authors.lastname: Avatapalle
authors.affiliation: 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.
authors.forename: Indraneel
authors.initials: I
authors.lastname: Banerjee
authors.affiliation: Department of Paediatric Endocrinology, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Rigby
authors.affiliation: Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester , Manchester , UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Vail
authors.affiliation: School of Mathematics, University of Manchester , Manchester , UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Foster
authors.affiliation: School of Mathematics, University of Manchester , Manchester , UK.
authors.forename: Christiana
authors.initials: C
authors.lastname: Charalambous
authors.affiliation: Department of Paediatric Endocrinology, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Bowden
authors.affiliation: Department of Paediatric Endocrinology, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK.
authors.forename: Raja
authors.initials: R
authors.lastname: Padidela
authors.affiliation: 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.
authors.forename: Leena
authors.initials: L
authors.lastname: Patel
authors.affiliation: 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.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ehtisham
authors.affiliation: Faculty of Life Sciences, University of Manchester , Manchester , UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Cosgrove
authors.affiliation: Faculty of Life Sciences, University of Manchester , Manchester , UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dunne
authors.affiliation: 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.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clayton
keywords: clinical trial; congenital hyperinsulinism; diazoxide; hypoglycemia; omega-3-polyunsaturated fatty acids