The Association between Low Serum Bilirubin and Carotid Atherosclerosis in Subjects with Type 2 Diabetes

Abstract

Background: Bilirubin prevents oxidative modification of low density lipoprotein, and may protect vessels from atherosclerosis. Several studies showed an inverse relationship between serum bilirubin and coronary artery disease. However, there are some needs to clarify the relationship between serum bilirubin and carotid atherosclerosis in type 2 diabetes, especially. Methods: A total of 346 type 2 diabetic patients, between 35 and 95 years of age (146 men and 200 women), were studied. Subjects with normal serum total bilirubin were divided into two groups, according to their serum total bilirubin levels (group I, total bilirubin ≥ 1.0 mg/dL [n = 59]; group II, total bilirubin ≤ 0.5 mg/dL [n = 76]). Carotid intima-media thickness (IMT) and plaque scores were measured by ultrasonography. Carotid atherosclerosis was defined by the presence of plaque or more than 1 mm of common carotid IMT. Results: Carotid IMT was positively correlated with age, duration of diabetes and hypertension, high sensitive C-reactive protein (hs-CRP) and fibrinogen, but, it was negatively correlated with bilirubin, gamma glutaryltransferase, albumin, hemoglobin, cystatin C and estimated-glomerular filtration rate (GFR) in all subjects. After controlling for sex, age and levels of hemoglobin, direct bilirubin only was negatively correlated with carotid IMT (r = -0.151, P = 0.034). Low serum total bilirubin group had a lot of female, long duration of diabetes and hypertension, higher hs-CRP, platelet counts, serum creatinine, HbA1c and homeostasis model assessmentinsulin resistance, lower albumin, hemoglobin, estimated-GFR and quantitative insulin sensitivity check index. Carotid IMT and plaque scores were significantly greater in low serum bilirubin group (0.785 ± 0.210 mm vs. 0.678 ± 0.146 mm, P < 0.01; 1.95 ± 2.56 vs. 1.03 ± 1.40, P < 0.05, respectively) than in the high serum bilirubin group. Multivariate logistic regression analysis showed that age, serum albumin and total bilirubin were independent associated factors for carotid atherosclerosis in type 2 diabetic women. Conclusion: Total bilirubin is inversely correlated with carotid atherosclerosis in type 2 diabetic patients, and it is an independent associated factor for carotid atherosclerosis in women. (Endocrinol Metab 27:126-131, 2012)

Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations

“…The results of this study support those of Park et al (129), who also showed higher high-sensitivity CRP (hs-CRP) and HOMA-IR in type II diabetic patients with lower serum bilirubin concentrations (Supplemental Table S1; entry 13). Carotid intima-media thickness, plaque scores, insulin, serum creatinine, estimated GFR (eGFR), period of diabetes, and hypertension were significantly improved in patients with higher bilirubin concentrations, especially in women (129). These findings indicate that bilirubin might protect from renal damage, possibly by inducing anti-inflammatory mechanisms related to complement activation and cytokine release (7, 81).…”

“…In addition, serum bilirubin was also negatively associated with insulin resistance [Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)] and C-reactive protein (CRP) (62,66). The results of this study support those of Park et al (129), who also showed higher high-sensitivity CRP (hs-CRP) and HOMA-IR in type II diabetic patients with lower serum bilirubin concentrations (Supplemental Table S1; entry 13). Carotid intima-media thickness, plaque scores, insulin, serum creatinine, estimated GFR (eGFR), period of diabetes, and hypertension were significantly improved in patients with higher bilirubin concentrations, especially in women (129).…”

Mildly Elevated Serum Bilirubin Levels Are Negatively Associated with Carotid Atherosclerosis among Elderly Persons

“…In198 hypertensive patients (104 men) aged 46–82 years, serum bilirubin levels were independently associated with carotid atherosclerosis in women and men, with odds ratios of 0.49 (95% CI, 0.28-0.71) and 0.66 (95% CI, 0.46–0.80) [28] . Among 346 type 2 diabetic patients (146 men) aged 35–95 years, serum bilirubin levels were independently associated with carotid IMT ( β = -0.34) [29] . In a 5-year prospectively study of 245 healthy individuals (98 men) aged 30–89 years at baseline, in subjects with plaque at entry, serum bilirubin as well as age, changes in eGFR, and the baseline levels of serum albumin dependently influenced the outcome of carotid plaque [30] .…”

Association between Total Bilirubin and Hemoglobin A1c in Korean Type 2 Diabetic Patients

“…Recent studies of its physiological importance have focused on its relationship with atherosclerotic diseases ( 6 ). Many studies have reported that higher serum bilirubin levels were related to decreased risks of CAD ( 7 , 8 ), carotid atherosclerosis ( 9 ), stroke ( 10 ), and peripheral arterial disease (PAD) ( 11 ).…”