Total serum bilirubin does not affect vascular reactivity in patients with diabetes

Abstract

Bilirubin may have a major role in the prevention of cardiovascular disease based on recent data regarding its anti-oxidant properties. We determined the relationship between total serum bilirubin and vascular reactivity in a large cohort of individuals with diabetes, a disease associated with known oxidant stress. We studied 302 individuals: 52 controls, 37 with type 1 diabetes, 213 with type 2 diabetes. High-resolution ultrasound was used to measure flow-mediated dilation (FMD; endothelium-dependent) and nitroglycerin-induced dilation (NID, endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure microvascular reactivity in the forearm skin before and after iontophoresis of acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent). Bilirubin levels were higher in the type 2 diabetes group (0.71 +/- 0.34 mg/dl) compared to controls (0.56 +/- 0.26 mg/dl, p < 0.0001). A weak inverse correlation was observed between bilirubin and FMD (r = -0.125, p = 0.032) and skin endothelium-dependent vasodilation (r = -0.157, p = 0.019). In multivariate analyses, however, these correlations were not statistically significant. There is no association between bilirubin levels and vascular reactivity in the macro- and microcirculation of individuals with diabetes. Bilirubin, therefore, does not correlate with predictors of cardiovascular risk in the diabetic population.

Figure 1

Total bilirubin levels were increased in the individuals with type 2 diabetes (T2 DM) when compared to healthy controls and individuals with type 1 diabetes (T1 DM). Results are presented as means ± SD. *Control and T1 DM vs T2 DM, p < 0.0001.

Figure 2

The skin perfusion response to iontophoresis of acetylcholine (endothelium-dependent vasodilation in the microcirculation) and sodium nitroprusside (endothelium-independent vasodilation in the microcirculation), and the brachial artery diameter change in response to reactive hyperemia (flow-mediated dilation, endothelium-dependent vasodilation in the macrocirculation) and nitroglycerin (nitroglycerin-induced dilation, endothelium-independent vasodilation in the macrocirculation) in controls, individuals with type 1 diabetes (T1 DM), and individuals with type 2 diabetes (T2 DM). Compared with controls, all groups with diabetes had impaired endothelium-dependent and independent vasodilation in both the macro (FMD and NID) and microcirculations (Ach and SNp). Results are presented as percent increase over baseline and expressed as means ± SD. *Control versus T1 DM and T2 DM, p < 0.0001; &: Control versus T1 DM and T2 DM, p = 0.002; ψ: Control versus T1 DM and T2 DM, p = 0.001.