title: Atazanavir improves cardiometabolic measures but not vascular function in patients with long-standing type 1 diabetes mellitus.
abstract: OBJECTIVE
  Vascular disease is the leading cause of morbidity and mortality in type 1 diabetes mellitus (T1DM). We previously demonstrated that patients with T1DM have impaired endothelial function, a forme fruste of atherosclerosis, as a result of increased oxidative stress. Bilirubin has emerged as a potent endogenous antioxidant with higher concentrations associated with lower rates of myocardial infarction and stroke.
  
  
  METHODS
  We tested the hypothesis that increasing endogenous bilirubin using atazanavir would improve cardiometabolic risk factors and vascular function in patients with T1DM to determine whether targeting bilirubin may be a novel therapeutic approach to reduce cardiovascular disease risk in this population. In this single-arm, open-label study, we evaluated blood pressure, lipid profile, and conduit artery function in fifteen subjects (mean age 45 ± 9 years) with T1DM following a 4-day treatment with atazanavir.
  
  
  RESULTS
  As anticipated, atazanavir significantly increased both serum total bilirubin levels (p < 0.0001) and plasma total antioxidant capacity (p < 0.0001). Reductions in total cholesterol (p = 0.04), LDL cholesterol (p = 0.04), and mean arterial pressure (p = 0.04) were also observed following atazanavir treatment. No changes were seen in either flow-mediated endothelium-dependent (p = 0.92) or nitroglycerine-mediated endothelium-independent (p = 0.68) vasodilation, measured by high-resolution B-mode ultrasonography at baseline and post-treatment.
  
  
  CONCLUSIONS
  Increasing serum bilirubin levels with atazanavir in subjects with T1DM over 4 days favorably reduces LDL and blood pressure but is not associated with improvements in endothelial function of conduit arteries.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Milian
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
authors.forename: Jonah P
authors.initials: JP
authors.lastname: Zuflacht
authors.forename: Caitlin
authors.initials: C
authors.lastname: Parmer
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Beckman
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D000069446:Atazanavir Sulfate / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000209:etiology; D001663:Bilirubin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D008078:Cholesterol, LDL / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D008078:Cholesterol, LDL; D000069446:Atazanavir Sulfate; D001663:Bilirubin