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Serum Total Bilirubin Levels Provide Additive Risk Information over the Framingham Risk Score for Identifying Asymptomatic Diabetic Patients at Higher Risk for Coronary Artery Stenosis
Jaechan Leem, Eun Hee Koh, Jung Eun Jang, Chang-Yun Woo, Jin Sun Oh, Min Jung Lee, Joon-Won Kang, Tae-Hwan Lim, Chang Hee Jung, Woo Je Lee, Joong-Yeol Park, Ki-Up Lee
Diabetes Metab J. 2015;39(5):414-423.   Published online October 22, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.5.414
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  • 7 Web of Science
  • 7 Crossref
AbstractAbstract PDFPubReader   
Background

The diagnosis of coronary artery disease (CAD) is often delayed in patients with type 2 diabetes. Serum total bilirubin levels are inversely associated with CAD. However, no studies have examined whether this can be used as a biochemical marker for identifying asymptomatic diabetic patients at higher risk for having obstructive CAD.

Methods

We performed a cross-sectional study of 460 consecutive asymptomatic patients with type 2 diabetes. All patients underwent coronary computed tomographic angiography, and their serum total bilirubin levels were measured. Obstructive CAD was defined as ≥50% diameter stenosis in at least one coronary artery.

Results

Serum total bilirubin tertiles showed an inverse association with the prevalence of obstructive CAD. In multivariate logistic regression analysis, the odds ratio for the highest versus the lowest tertile of total bilirubin was 0.227 (95% confidence interval [CI], 0.130 to 0.398), and an increment of 1 µmol/L in serum total bilirubin level was associated with a 14.6% decrease in obstructive CAD after adjustment for confounding variables. Receiver operating characteristic curve analysis showed that the area under the curve for the Framingham Risk Score (FRS) plus serum total bilirubin level was 0.712 (95% CI, 0.668 to 0.753), which is significantly greater than that of the FRS alone (P=0.0028).

Conclusion

Serum total bilirubin level is inversely associated with obstructive CAD and provides additive risk information over the FRS. Serum total bilirubin may be helpful for identifying asymptomatic patients with type 2 diabetes who are at higher risk for obstructive CAD.

Citations

Citations to this article as recorded by  
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Review
The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular Complications
Shuji Sasaki, Toyoshi Inoguchi
Diabetes Metab J. 2012;36(4):255-261.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.255
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AbstractAbstract PDFPubReader   

Oxidative stress has been paid increasing attention to as an important causative factor for diabetic vascular complications. Among possible various sources, accumulating evidence has indicated that NAD(P)H oxidase may be the most important source for reactive oxygen species production in diabetic vascular tissues. The mechanisms underlying activation and up-regulation of NAD(P)H oxidase has been supposed to be mediated by high glucose-induced protein kinase C (PKC) activation. In this review article, activation of local renin-angiotensin II system induced by chymase activation is also shown to amplify such a PKC-dependent activation of NAD(P)H oxidase. Additionally, human evidence showing the beneficial effect of antioxidants on diabetic vascular complications. Bilirubin has been recognized as a strong endogenous antioxidant. Here markedly lower prevalence of vascular complications is shown in diabetic patients with Gilbert syndrome, a congenital hyperbilirubinemia, as well as reduced markers of oxidative stress and inflammation. Lastly, statin, angiotensin II receptor blocker, chymase inhibitor, bilirubin and biliverdin, PKC β isoform inhibitor, and glucagon-like peptide-1 analog, are shown to serve as antioxidants and have some beneficial effect on diabetic vascular complications, via inhibiting PKC-NAD(P)H oxidase activation, supporting the notion that this mechanism may be an effective therapeutic target for preventing diabetic vascular complications.

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Original Articles
The Relationship among Homocysteine, Bilirubin, and Diabetic Retinopathy
Ho Chan Cho
Diabetes Metab J. 2011;35(6):595-601.   Published online December 26, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.6.595
  • 65,535 View
  • 44 Download
  • 27 Crossref
AbstractAbstract PDFPubReader   
Background

Diabetic retinopathy is a common microvascular complication of diabetes mellitus (DM) and the leading cause of blindness in adults. Homocysteine, a risk factor with toxic effects on vascular endothelial cells, and bilirubin, a protectant with antioxidant and anti-inflammatory properties on the vasculature, have been reported to be linked to vaso-occlusive disorders. Therefore, the author of the present study investigated the association between the levels of plasma homocysteine and serum total bilirubin and the incidence of diabetic retinopathy as a chronic microvascular complication in patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 102 patients with T2DM who visited our hospital from January 2009 to January 2010 were assessed.

Results

Of the 102 patients, the prevalence of diabetic retinopathy was 67 cases (65.7%) according to clinical ophthalmic examination. The duration of DM (P<0.001), age (P=0.003), fasting blood glucose (P=0.045) and urine albumin-creatinine ratio (P=0.015) in univariate analysis and plasma homocysteine level (P=0.038), duration of DM (P=0.001), and total bilirubin level (P=0.012) in multiple logistic regression analysis were statistically significantly associated with the incidence of diabetic retinopathy.

Conclusion

The present study indicates that homocysteine and bilirubin may be useful biomarkers for increased risk of diabetic retinopathy since retinopathy in patients with T2DM was linked to higher plasma homocysteine level and decreased serum total bilirubin level.

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Relationship Between Serum Bilirubin Levels and Coronary Atherosclerosis in Patients with Type 2 Diabetes.
Jun Sung Moon, Woo Jin Chang, Chan Hee Lee, Ji Eun Lee, Kyung Ah Chun, Ji Sung Yoon, Ihn Ho Cho, Hyoung Woo Lee, Kyu Chang Won
Korean Diabetes J. 2008;32(4):338-345.   Published online August 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.4.338
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AbstractAbstract PDF
BACKGROUND
Lipid oxidation and formation of oxygen radicals have been identified to be the important factors of atherogenesis. Because bilirubin, a potent physiological antioxidant inhibits lipid oxidation, it is suggested that low serum concentrations of bilirubin is associated with atherosclerosis. The aim of this study was to evaluate the relationship between bilirubin levels and coronary atherosclerosis. METHODS: The coronary calcium score (CCS) of 172 subjects (male 63, mean age 60.5 +/- 1.0) with type 2 diabetes were evaluated in Yeungnam University Hospital between January 2005 and February 2007. The subjects were divided into two groups with CCS 10 as the cut off. RESULTS: Higher CCS was significantly associated with lower bilirubin (P < 0.05), but after adjusted with age, no longer correlation were seen (P = 0.121). To determine the relationship between subclinical coronary atherosclerosis and bilirubin, the subjects with previous history of cardiovascular disease were excluded. In 138 subjects (male 54, mean age 58.4 +/- 1.1), higher CCS was significantly associated with lower levels of bilirubin. After adjusted with age, duration of diabetes, and history of hypertension, CCS was also inversely related with bilirubin (P < 0.05). CONCLUSION: These results suggest that lower levels of bilirubin might be considered as a risk factor of coronary artery disease, especially in type 2 diabetics without cardiovascular disease.

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