title: Protocol for systematic review of evidence on the determinants and influence of early glycaemic control in childhood-onset type 1 diabetes.
abstract: BACKGROUND
  Landmark studies in adult-onset type 1 diabetes (T1D) populations indicate that improved glycaemic control through use of intensive insulin therapy is strongly associated with reduced risk for the development of diabetes-related complications and mortality in later years. However, it is unclear whether these associations can be extrapolated to childhood-onset T1D, given the influence of other important biological and psychosocial determinants of glycaemic control, particularly during adolescence. The aims of the review are (1) to investigate the impact of early glycaemic control (within the first 2 years after diagnosis) on subsequent glycaemic trends and risk of complications during the life course of childhood-onset T1D and (2) to identify the predictors of early glycaemic control in children and young people (0-25 years).
  
  
  METHODS
  The methods used in this study are systematic identification, review and mapping of quantitative (intervention and observational) and qualitative literature; assessing the effect and predictors of early glycaemic control in T1D (diagnosed ≤18 years) on risk or prevalence of later complications. An iterated search strategy, with no language or period restrictions, was applied to identify studies from six electronic databases. This will be supplemented by hand-searching (reference lists and contacting authors of studies meeting the inclusion criteria). Studies assessing glycaemic control within the first 2 years of diagnosis in children (at baseline) will be quality-assessed against predefined criteria and mapped descriptively to future health outcomes. Extracted data will be analysed and synthesised using narrative and forest plots or harvest plots for quantitative evidence and thematic analyses for qualitative studies. To get a deeper understanding of the predictors of early glycaemic control in reducing complications in childhood and adult life, we will integrate qualitative and quantitative evidence using mixed methods or parallel synthesis approach.
  
  
  CONCLUSIONS
  These linked reviews will be the first to systematically investigate the effects of early glycaemic control and integrate both the quantitative and qualitative evidence on predictors of early glycaemic control in childhood-onset T1D in reducing future diabetes complications. This will help identify and map current research and inform development of effective future interventions.
  
  
  BACKGROUND
  PROSPERO CRD42015024546.
authors.affiliation: Institute of Child Health, University College London, London, UK. veena.paes.14@ucl.ac.uk.|Institute of Public Health, University of Cambridge, Cambridge, UK. veena.paes.14@ucl.ac.uk.
authors.forename: Veena
authors.initials: V
authors.lastname: Mazarello Paes
authors.affiliation: Institute of Child Health, University College London, London, UK. d.charalampopoulos@ucl.ac.uk.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Charalampopoulos
authors.affiliation: Institute of Child Health, University College London, London, UK. a.khanolkar@ucl.ac.uk.|Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. a.khanolkar@ucl.ac.uk.
authors.forename: Amal R
authors.initials: AR
authors.lastname: Khanolkar
authors.affiliation: Institute of Child Health, University College London, London, UK. David.Taylor-Robinson@liverpool.ac.uk.|University of Liverpool, Liverpool, UK. David.Taylor-Robinson@liverpool.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Taylor-Robinson
authors.affiliation: Institute of Child Health, University College London, London, UK. r.viner@ucl.ac.uk.
authors.forename: Russell
authors.initials: R
authors.lastname: Viner
authors.affiliation: Oxford Children's Hospital, University of Oxford, Oxford, UK. julie.edge@paediatrics.ox.ac.uk.
authors.forename: Julie
authors.initials: J
authors.lastname: Edge
authors.affiliation: Institute of Child Health, University College London, London, UK. terence.stephenson@ucl.ac.uk.
authors.forename: Terence
authors.initials: T
authors.lastname: Stephenson
authors.affiliation: Institute of Child Health, University College London, London, UK. rakesh.amin@ucl.ac.uk.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Amin
mesh_terms: D017668:Age of Onset; D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D048909:Diabetes Complications / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D012107:Research Design; D000078202:Systematic Reviews as Topic
chemical_list: D001786:Blood Glucose; D007328:Insulin