title: Insulin resistance and inflammation are a cause of hyperglycemia after pediatric cardiopulmonary bypass surgery.
abstract: OBJECTIVE
  Hyperglycemia is common after pediatric cardiopulmonary bypass (CPB) surgery and is attributed to a state of insulin resistance. We examined the role of CPB-induced inflammation on postoperative plasma glucose, insulin, and the glucose-to-insulin ratio, which was used as a marker of insulin resistance; a decrease in the ratio reflects increased resistance.
  
  
  METHODS
  We conducted an ancillary study on a previously published randomized trial of children undergoing CPB surgery. Serial blood glucose, insulin, and cytokines were drawn after CPB and at selected intervals for up to 48 hours after surgery. The primary outcome was plasma insulin levels and glucose-to-insulin ratio. Glucose delivery and feeding status were monitored for potential modifying effects.
  
  
  RESULTS
  The 299 children studied were predominantly male (55%) with a median age of 2.7 (interquartile range [IQR]: 0.5-6.5) years, and weight of 12.6 (IQR: 6.4-10.8) kg. Operations had a median Society of Thoracic Surgery-European Association for Cardio-Thoracic Surgery complexity score of 1 (IQR: 1-2) and CPB time of 82 (IQR: 58-122) minutes. Hyperglycemia occurred in 85% of subjects; odds of hyperglycemia peaked at 6 hours after CPB. Plasma glucose was associated with increased insulin and a lower glucose-to-insulin ratio. Increased interleukin (IL)-6 concentrations were associated with increased glucose (estimate [EST]: 0.55 (±0.13) mmol/L; P < .001) and insulin (EST: 1.14 (±0.12) μmol/L; P < .001) in linear regression adjusted for repeated measures. Paradoxically, increased cytokines were associated with an increased glucose-to-insulin ratio (EST: 0.21 (±0.03) mmol/μmol; P < .001).
  
  
  CONCLUSIONS
  Hyperglycemia after pediatric CPB surgery is associated with hyperinsulinemia, which may reflect insulin resistance in some patients. Inflammation induced by CPB may play a causative role in insulin resistance.
authors.affiliation: Department of Critical Care Medicine, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: alejandro.floh@sickkids.ca.
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Floh
authors.affiliation: Department of Pediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Cedric
authors.initials: C
authors.lastname: Manlhiot
authors.affiliation: Department of Pediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Redington
authors.affiliation: Department of Pediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Brian W
authors.initials: BW
authors.lastname: McCrindle
authors.affiliation: Department of Pediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Clarizia
authors.affiliation: Division of Cardiovascular Surgery, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Caldarone
authors.affiliation: Department of Critical Care Medicine, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Schwartz
mesh_terms: D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D007223:Infant; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008297:Male; D009752:Nutritional Status; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C508600:IL6 protein, human; D018836:Inflammation Mediators; D007328:Insulin; D015850:Interleukin-6
keywords: cardiopulmonary bypass; hyperglycemia; hyperinsulinemia; insulin resistance; pediatrics