Abstract
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.
Original language | English (US) |
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Pages (from-to) | 709-715 |
Number of pages | 7 |
Journal | Acta Diabetologica |
Volume | 52 |
Issue number | 4 |
DOIs | |
State | Published - Aug 25 2015 |
Externally published | Yes |
Keywords
- Bilirubin
- Endothelium
- Oxidative stress
- Type 1 diabetes
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Endocrinology