Atazanavir improves cardiometabolic measures but not vascular function in patients with long-standing type 1 diabetes mellitus.

Milian J, Goldfine AB, Zuflacht JP, Parmer C, Beckman JA
Acta Diabetol. 2015 52 (4): 709-15

PMID: 25563478 · PMCID: PMC4496330 · DOI:10.1007/s00592-014-0708-6

AIMS - 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.

CONCLUSION - 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.

MeSH Terms (17)

Adult Antioxidants Atazanavir Sulfate Atherosclerosis Bilirubin Blood Pressure Cardiovascular System Cholesterol, LDL Diabetes Mellitus, Type 1 Endothelium, Vascular Female Humans Male Middle Aged Oxidative Stress Risk Factors Vasodilation

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