title: Hyperglycaemia results from beta-cell dysfunction in critically ill children with respiratory and cardiovascular failure: a prospective observational study.
abstract: BACKGROUND
  Hyperglycaemia is common in critical illness and associated with poor outcome. Glycaemic control using insulin may decrease morbidity and mortality. Many questions remain about the cause of critical illness hyperglycaemia (CIH). Our objective was to investigate the endocrinological basis of paediatric CIH.
  
  
  METHODS
  C-peptide and blood glucose (BG) levels were assessed in 41 children aged 2 to 18 years old who were admitted to our paediatric intensive care unit (PICU). Patients who developed CIH, defined as persistent BG above 7.7 mmol/L, were treated with insulin infusion to achieve BG levels between 4.4 and 7.7 mmol/L. C-peptide levels were compared with respect to CIH development and degree of organ failure in all patients. Respiratory and cardiovascular failure were defined as need for mechanical ventilation and need for vasoactive infusions, respectively. Clinical and laboratory parameters, including c-peptide levels, were assessed.
  
  
  RESULTS
  Of 41 children enrolled, 18 had respiratory failure only, 11 had both respiratory and cardiovascular failure, and 12 had neither respiratory or cardiovascular failure. Nine patients with respiratory failure only, 10 with both respiratory and cardiovascular failure, and none with no respiratory or cardiovascular failure developed CIH. Patients with CIH and respiratory and cardiovascular failure (n = 10) had very low c-peptide levels (4.4 ng/mL) despite significantly elevated mean BG levels (10.8 mmol/L), while those with CIH and respiratory failure only had very high c-peptide levels (11.5 ng/mL) with mean BG of 9.9 mmol/L. Low endogenous insulin production in those with respiratory and cardiovascular failure was associated with rapid onset of CIH, illness severity, higher insulin requirement and longer mechanical ventilation days, PICU length of stay and CIH duration.
  
  
  CONCLUSIONS
  Primary beta-cell dysfunction as defined by low endogenous c-peptide production appears to be prevalent in critically ill children with both respiratory and cardiovascular failure who develop CIH, whereas elevated insulin resistance appears to be the prominent cause of CIH in children with respiratory failure only. Our finding that beta-cell dysfunction is present in a subset of critically ill children with CIH challenges the assertion from adult studies that CIH is primarily the result of elevated insulin resistance.
authors.affiliation: Department of Pediatrics, Division of Pediatric Critical Care Medicine, Emory University School of Medicine, Children's Healthcare of Atlanta at Egleston, Atlanta, GA 30322, USA. catherine.preissig@choa.org
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Preissig
authors.forename: Mark R
authors.initials: MR
authors.lastname: Rigby
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000628:therapy; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D011446:Prospective Studies; D012131:Respiratory Insufficiency / Q000150:complications / Q000503:physiopathology* / Q000628:therapy