title: Favorable effects of insulin sensitizers pertinent to peripheral arterial disease in type 2 diabetes: results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.
abstract: OBJECTIVE
  The aim of this manuscript was to report the risk of incident peripheral arterial disease (PAD) in a large randomized clinical trial that enrolled participants with stable coronary artery disease and type 2 diabetes and compare the risk between assigned treatment arms.
  
  
  METHODS
  The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomly assigned participants to insulin sensitization (IS) therapy versus insulin-providing (IP) therapy for glycemic control. Results showed similar 5-year mortality in the two glycemic treatment arms. In secondary analyses reported here, we examine the effects of treatment assignment on the incidence of PAD. A total of 1,479 BARI 2D participants with normal ankle-brachial index (ABI) (0.91-1.30) were eligible for analysis. The following PAD-related outcomes are evaluated in this article: new low ABI≤0.9, a lower-extremity revascularization, lower-extremity amputation, and a composite of the three outcomes.
  
  
  RESULTS
  During an average 4.6 years of follow-up, 303 participants experienced one or more of the outcomes listed above. Incidence of the composite outcome was significantly lower among participants assigned to IS therapy than those assigned to IP therapy (16.9 vs. 24.1%; P<0.001). The difference was significant in time-to-event analysis (hazard ratio 0.66 [95% CI 0.51-0.83], P<0.001) and remained significant after adjustment for in-trial HbA1c (0.76 [0.59-0.96], P=0.02).
  
  
  CONCLUSIONS
  In participants with type 2 diabetes who are free from PAD, a glycemic control strategy of insulin sensitization may be the preferred therapeutic strategy to reduce the incidence of PAD and subsequent outcomes.
authors.affiliation: Corresponding author: Andrew D. Althouse, ada25@pitt.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Althouse
authors.forename: J Dawn
authors.initials: JD
authors.lastname: Abbott
authors.forename: Kim
authors.initials: K
authors.lastname: Sutton-Tyrrell
authors.forename: Alan D
authors.initials: AD
authors.lastname: Forker
authors.forename: Manuel S
authors.initials: MS
authors.lastname: Lombardero
authors.forename: L Virginia
authors.initials: LV
authors.lastname: Buitrón
authors.forename: Ivan
authors.initials: I
authors.lastname: Pena-Sing
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Maria Mori
authors.initials: MM
authors.lastname: Brooks
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin