title: Continuous subcutaneous insulin infusion versus multiple daily injections: the impact of baseline A1c.
abstract: OBJECTIVE
  Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1 diabetes. Thus, a comparison of efficacy between CSII and MDII should be undertaken only in studies that used rapid-acting analogs for both intensive regimens.
  
  
  METHODS
  We performed a pooled analysis of the randomized controlled trials that compared CSII and optimized MDII therapy using rapid-acting analogs in adults with type 1 diabetes.
  
  
  RESULTS
  The three studies that met inclusion criteria provided data on 139 patients, representing 596 patient-months for CSII and 529 patient-months for MDII. Mean age was 38.5 years, with duration of diabetes of 18.0 years. The studies differed significantly in mean baseline A1c (7.95, 8.20, and 9.27%). The pooled estimate of treatment effect comparing the percentage reduction in A1c by CSII with that by MDII (CSII - MDII) was 0.35% (95% CI -0.10 to 0.80, P = 0.08) using a random effect to account for heterogeneity between studies. Importantly, the interaction between baseline A1c and treatment modality emerged as an independent predictor of treatment effect (CSII - MDII) (P = 0.002). The relative benefit of CSII over MDII was found to increase with higher baseline A1c. A model derived from these data predicts that in a patient with a baseline A1c of 10%, CSII would reduce the A1c by an additional 0.65% compared with MDII. Conversely, there would be no A1c benefit of CSII compared with MDII if baseline A1c were 6.5%. There was no significant difference between CSII and MDII in the rate of hypoglycemic events.
  
  
  CONCLUSIONS
  When using rapid-acting insulin analogs in CSII and MDII regimens in adult patients with type 1 diabetes, insulin pump therapy is associated with better glycemic control, particularly in those individuals with higher baseline A1c. Thus, CSII emerges as an important modality for implementing intensive therapy and may be uniquely advantageous in patients with poor glycemic control.
authors.affiliation: Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
authors.forename: Jackie
authors.initials: J
authors.lastname: Hochman
authors.forename: J Hans
authors.initials: JH
authors.lastname: DeVries
authors.forename: Helene
authors.initials: H
authors.lastname: Hanaire-Broutin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heine
authors.forename: Vincent
authors.initials: V
authors.lastname: Melki
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007267:Injections; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin