title: Clinical review: Hypoglycemia with intensive insulin therapy: a systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections.
abstract: BACKGROUND
  Hypoglycemia limits the efficacy of intensive insulin therapy. The extent to which continuous insulin infusion (CSII) overcomes this limitation is unclear.
  
  
  OBJECTIVE
  The aim was to summarize evidence on the effect of CSII and multiple daily injections (MDIs) on glycemic control and hypoglycemia.
  
  
  METHODS
  We searched electronic databases between 2002 and March 2008.
  
  
  METHODS
  We selected published randomized trials of CSII vs. MDI.
  
  
  METHODS
  Reviewers working in duplicate and independently extracted study characteristics and quality and differences in glycosylated hemoglobin (HbA1c) and hypoglycemic events.
  
  
  RESULTS
  We found 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study HbA1c levels. Patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, -0.2%; 95% confidence interval (CI), -0.3, -0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95% CI, 0.23, 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95% CI 0.33, 2.03). Adolescents and adults with type 1 diabetes enrolled in crossover trials had nonsignificantly fewer minor hypoglycemia episodes per patient per week (-0.08; 95% CI, -0.21, 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95% CI, 0.16, 1.20; P(interaction) = 0.03). Outcomes were not different in patients with type 2 diabetes.
  
  
  CONCLUSIONS
  Contemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data.
authors.affiliation: Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Mitra M
authors.initials: MM
authors.lastname: Fatourechi
authors.forename: Yogish C
authors.initials: YC
authors.lastname: Kudva
authors.forename: M Hassan
authors.initials: MH
authors.lastname: Murad
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Elamin
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Tabini
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
mesh_terms: D003920:Diabetes Mellitus / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D007332:Insulin Infusion Systems; D016032:Randomized Controlled Trials as Topic
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human