Lower Serum Bilirubin Levels Research Articles

8626 Associations Between Low Serum Bilirubin Levels and the Progression of Diabetic Kidney Disease in Individuals with Type 2 Diabetes, Including Those in a Normoalbuminuric State

Abstract Disclosure: E. Kim: None. Y. Cho: None. O. Hong: None. K. Jo: None. J. Han: None. S. Moon: None. Objective: This study aimed to investigate the potential correlation between serum bilirubin levels and the progression of diabetic nephropathy, assessing whether low serum bilirubin levels are associated with a decline in renal function, while considering the baseline albumin excretion status. Methods: The longitudinal observation, spanning 11 years, involved 1167 Korean subjects aged 20 years or older, diagnosed with type 2 diabetes mellitus (T2DM), and having a baseline estimated glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m2. Albuminuria was assessed by the 24-hour urinary albumin to creatinine excretion rate (ACR) and categorized into normoalbuminuria (ACR <30 mg/g), micro- or macroalbuminuria (ACR >300/g). Cox regression analysis was employed to explore connections between serum bilirubin levels and eGFR decline ≥40%, with adjustments for potential confounding variables. Results: Over a median follow-up of 8.2 years, 128 individuals experienced a decline in eGFR >40%. The hazard ratio (HR) of incident GFR decline was 1.72 (95% CI: 1.04-2.85, P=0.036) in the lowest total bilirubin (TB) tertile compared to the highest TB tertile after multivariable adjustment. When stratified by baseline albuminuria status, low bilirubin levels were significantly associated with eGFR decline, even in the normoalbuminuria group (HR: 2.21, 95% CI: 1.26-3.90, P=0.006), with a gradually increasing risk according to the absence of low TB levels and albuminuria (HR: 2.92, 95% CI: 1.65-5.19, P<0.001), and low TB levels and albuminuria (HR: 3.01, 95% CI: 1.65-5.46, P<0.001). Conclusion: Low serum TB levels are associated with an increased risk of rapid GFR decline in Korean patients with T2DM. Serum bilirubin levels may serve as a prognostic marker for the development and progression of diabetic kidney disease. Presentation: 6/1/2024

Relation of Serum Bilirubin in Physiological Range with Spot Urine Albumin to Creatinine Ratio and eGFR Among Diabetic Patients with or without Nephropathy

Recent studies have suggested a potential role of bilirubin as an antioxidant to protect diabetic patients from hyperglycemia-induced oxidative stress thereby preventing diabetic complications. Diabetic nephropathy is a serious microvascular complication which is determined by increased urinary albumin to creatinine ratio and reduced eGFR. The present work aimed to study the relation of the simple biochemical parameter of serum bilirubin level with the estimated glomerular filtration rate (eGFR) and spot urine albumin to creatinine ratio in diabetic patients with or without nephropathy. This cross sectional study was done in the department of Biochemistry and Molecular Biology, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) Academy from July 2017 to June 2018. We have taken 63 diabetic patients without nephropathy and 63 diabetic patients with nephropathy.Data about clinical and biochemical parameters (blood pressure, BMI, fasting serum glucose, estimated GFR, serum bilirubin and spot urine ACR etc.) were measured by appropriate methods. We used student’s t test and Pearson’s correlation coefficient to detect the relationship of serum bilirubin with other variables All statistical tests were considered at 5% level of significance. We found diabetic patients with nephropathy have significantly lower serum bilirubin (p<0.001) than diabetic patients without nephropathy (0.46±0.18 and 0.64± 0.21 mg/d respectively). Pearson’s correlation test showed that serum bilirubin positively correlated with eGFR (r=0.312, p=0.013) in diabetic patients with nephropathy. This study concluded that low serum bilirubin level is associated with eGFR in diabetic patients with nephropathy.
 Bangladesh J Med Biochem 2019; 12(2): 16-22

Causal inference between serum bilirubin levels and juvenile idiopathic arthritis-associated uveitis: A bidirectional Mendelian randomization study.

Several observational studies have suggested an association between low serum bilirubin levels and Behçet's disease uveitis. However, the causal inference between bilirubin level and juvenile idiopathic arthritis-associated uveitis (JIAU) remains ambiguous. We investigated the potential causal relationship between serum bilirubin levels and JIAU using a bidirectional two-sample Mendelian randomization (MR) framework. We systemically integrated summary-level data from published large-scale genome-wide association studies on bilirubin level and JIAU in a Caucasian British population. To determine the causal effect of bilirubin level on JIAU, we constructed strong instrumental variables using 47 and 80 single-nucleotide polymorphisms (SNPs) specific to direct bilirubin and total bilirubin levels, respectively. For reverse causal inference, seven SNPs associated with JIAU were included in our study. Multiple complementary methods were further performed to evaluate the robustness of MR estimates. The inverse-variance weighted estimate did not show any significant causal associations of genetically predicted serum direct or total bilirubin level with the risk of JIAU (odds ratio [OR]: 1.010, 95% confidence interval [CI]: 0.750-1.359, p = 0.947; OR: 0.867, 95% CI: 0.688-1.093; p = 0.227, respectively). MR-Egger and weighted median methods also obtained similar associations. Additionally, the results of reverse MR analyses using JIAU as exposure showed no associations of genetically predicted risk of JIAU with serum bilirubin levels (p > 0.05). In sensitivity analysis, the causal estimate between serum bilirubin levels and JIAU did not differ when SNPs associated with possible confounders were omitted. Genetic evidence from our bidirectional analysis did not support a causal association between serum bilirubin levels and JIAU risk in the Caucasian British population. Future large-scale studies should be conducted to validate these findings and explore any causal effects on the disease process.

Association between serum bilirubin and estimated glomerular filtration rate in diabetic patients with chronic kidney disease

Background and objectives: Hyperglycemia induces oxidative stress in diabetic patients by increasing reactive oxygen species production, which ultimately damage the cells and cause micro and macrovascular complications including diabetic nephropathy. Increased serum bilirubin level, within physiological range, can inhibit oxidative stress; thereby, preventing development of diabetic nephropathy. The aim of this study was to find out association between serum bilirubin and estimated glomerular filtration rate (eGFR) in diabetic patients with or without chronic kidney disease (CKD). Materials and method: Both male and female participants aged 30 to 60 years were enrolled in the study. Enrolled participants included healthy individuals (Group-1), diabetic patients without CKD (Group-2) and diabetic patients with CKD (Group-3). Clinical and biochemical parameters namely blood pressure, body mass index (BMI), fasting blood glucose (FBG), HbA1c, eGFR, serum bilirubin and spot urine ACR were measured by appropriate methods. Pearson’s correlation coefficient, ANOVA and multiple linear regression models were used to analyze the data. Result: Total 189 respondents were enrolled in 3 study groups. Each group consisted of 63 cases. Of the 63 cases in Group-3, 49 and 14 belonged to CKD stage 3 and stage 4 respectively. The mean (± SD) serum bilirubin levels of healthy individuals, diabetic patients without CKD and diabetic patients with CKD were 0.66 ± 0.31, 0.64 ± 0.21, 0.46±0.18 mg/dL respectively. Mean serum bilirubin was significantly low (p<0.001) in diabetic patients with CKD compared to healthy and diabetics without CKD. A Stepwise multiple regression analysis using eGFR as an objective variable adjusted for risk factors as explanatory variables, showed that serum bilirubin (β=0.323, p<0.001) was significantly associated with eGFR, in addition to age, BMI, HbA1c and urinary ACR. Conclusion: The study has demonstrated that low serum bilirubin level is associated with CKD in diabetic patients and it could be used as a simple marker for CKD in diabetics. IMC J Med Sci. 2024; 18(1):006. DOI: https://doi.org/10.55010/imcjms.18.006 *Correspondence: Tanzia Tahfim, Department of Biochemistry, Shaheed Monsur Ali, Medical College, Uttara, Dhaka-1230, Bangladesh. Email: tanzia.uamc@gmail.com

Stronger Neo‐Minophagen C (SNMC): A stronger adjuvant for TACE?

Stronger <scp>Neo‐Minophagen</scp> C (<scp>SNMC</scp>): A stronger adjuvant for <scp>TACE</scp>?

Suppressing Hepatic UGT1A1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways and Lipid Species and Improves Fatty Liver Disease.

Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and reduced plasma levels of the bilirubin catabolized product, urobilin. We show that GNUR decreased liver fat content and ceramide production via lipidomics and lowered fasting blood glucose and insulin levels. We performed extensive kinase activity analyses using our PamGene PamStation kinome technology and found a reorganization of the kinase pathways and a significant decrease in inflammatory mediators with GNUR versus CTRL treatments. These results demonstrate that GNUR increases plasma bilirubin and reduces plasma urobilin, reducing NAFLD and inflammation and improving overall liver health. These data indicate that UGT1A1 antagonism might serve as a treatment for NAFLD and may improve obesity-associated comorbidities.

Relationship between serum indirect bilirubin levels and skeletal muscle mass in older male and female patients with type 2 diabetes

We previously showed that low serum bilirubin levels are associated with disability in quality of daily living in older patients with diabetes. However, the underlying mechanism is not fully understood. The aim of this study is to assess the relationship between serum bilirubin levels and skeletal muscle mass in older patients with type2 diabetes. A total of 272 older patients with type2 diabetes (152 male and 120 female) aged 60 years and over were continuously recruited from April 2020 to July 2020. Body composition was evaluated by bioelectrical impedance analysis. The skeletal muscle mass index (SMI) was calculated as appendicular muscle mass divided by height squared (m2). The SMI was markedly lower in old-old patients (aged 75 years and over) than in young-old patients (aged 60-74 years) in both male and female (7.1 ± 0.8 kg/m2 vs 7.6 ± 0.9 kg/m2, P<0.001; 5.5 ± 0.9 kg/m2 vs 6.3 ± 0.8 kg/m2, P<0.001, respectively). Multivariate regression analysis showed that the SMI was associated with body mass index (BMI) (p<0.001) and age (p = 0.048) in male young-old patients, while it was associated with BMI (p<0.001), age (p = 0.008), and serum indirect bilirubin levels (p = 0.038) in male old-old patients. In female, the SMI was associated with BMI (p<0.001) and age (p = 0.042) in young-old patients and associated with BMI alone (p<0.001) in old-old patients. Serum indirect bilirubin levels may be associated with the decreased skeletal muscle mass in male older patients (aged 75 years and over) with type 2 diabetes.

Bilirubin levels and kidney function decline: An analysis of clinical trial and real world data.

ObjectiveTo evaluate if previously found associations between low serum bilirubin concentration and kidney function decline is independent of hemoglobin and other key confounders.Research design and methodsClinical trial data from the SAVOR-TIMI 53 trial as well as the UK primary care electronic healthcare records, Clinical Practice Research Datalink (CPRD), were used to construct three cohorts of patients at risk of chronic kidney disease (CKD). The randomized clinical trial (RCT) cohort from the subset of SAVOR-TIMI 53 trial consisted of 10,555 type-2 diabetic patients with increased risk of cardiovascular disease. The two observational data cohorts from CPRD consisted of 71,104 newly diagnosed type-2 diabetes (CPRD-DM2) and 82,065 newly diagnosed hypertensive (CPRD-HT) patients without diabetes. Cohorts were stratified according to baseline circulating total bilirubin levels to determine association on the primary end point of a 30% reduction from baseline in estimated glomerular filtration rate (eGFR) and the secondary end point of albuminuria.ResultsThe confounder adjusted hazard ratios of the subpopulation with lower than median bilirubin levels compared to above median bilirubin levels for the primary end point were 1.18 (1.02–1.37), 1.12 (1.05–1.19) and 1.09 (1.01–1.17), for the secondary end point were 1.26 (1.06–1.52), 1.11 (1.01–1.21) and 1.18 (1.01–1.39) for SAVOR-TIMI 53, CPRD-DM2, CPRD-HT, respectively.ConclusionOur findings are consistent across all cohorts and endpoints: lower serum bilirubin levels are associated with a greater kidney function decline independent of hemoglobin and other key confounders. This suggests that increased monitoring of kidney health in patients with lower bilirubin levels may be considered, especially for diabetic patients.

Serum Bilirubin Is Correlated With the Progression of IgA Vasculitis With Nephritis.

Background: Bilirubin has been identified as an endogenous antioxidant and cellular protectant. The present study was performed to clarify the potential influence of serum bilirubin on IgA vasculitis with nephritis (IgAV-N).Methods: One hundred and eighty-nine IgAV-N patients over 14 years old were enrolled. The patients were divided into two groups by the optimum cut-off value calculated by ROC curve. The composite endpoints were defined as a 60% decline in estimate glomerular filtration rate (e-GFR), end-stage renal disease (ESRD) and/or death. Kaplan-Meier (K-M) analysis and multivariate Cox analysis were carried out to determine the predictors for renal outcomes. In order to eliminate the influence of different baseline data, a 1:2 propensity score (PS) match was performed to make the results comparable and convictive.Results: The baseline data suggested that patients in low serum bilirubin group had significantly higher levels of systolic blood pressure, proteinuria, serum creatinine and crescent formation ratio and lower levels of serum albumin and hemoglobin. Renal survival analysis indicated that lower serum bilirubin levels were significantly correlated with a poorer prognosis. Multivariate Cox analysis demonstrated that the higher level of serum bilirubin was an independent protective factor for renal survival (HR, 0.172; 95% CI, 0.030–0.991; P = 0.049). After PS matching, the baseline characters of two groups had no statistical differences. Similar outcomes were demonstrated in K-M curve and the multivariate Cox analysis.Conclusion: Elevated bilirubin levels might be related to the favorable renal outcomes.

Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption.

Studies increasingly show that ulcerative colitis (UC) is a consequence of an imbalance between oxidative stress and antioxidant capacity. Bilirubin exerts an anti-inflammatory effect by scavenging reactive oxygen species (ROS), although the exact mechanism is not completely understood. The aim of this study was to determine the role of serum bilirubin in UC using patient data and a mouse model of dextran sodium sulfate (DSS)-induced colitis. We found that low levels of serum bilirubin correlated to a higher risk of UC in a retrospective case-control population. Pre-treatment with exogenous unconjugated bilirubin (UCB) significantly enhanced colonic bilirubin absorption in mice, and attenuated the DSS-induced body weight loss, colon shortening and histopathological damage. Mechanistically, bilirubin prevented the infiltration of inflammatory cells, and decreased the levels of myeloperoxidase and pro-inflammatory cytokines in the serum and colon. Moreover, bilirubin inhibited ROS and malondialdehyde production, scavenged superoxide anions (O2 ·−) from the colon and enhanced the total antioxidant capacity. In conclusion, exogenous UCB attenuated DSS-induced colitis by directly scavenging O2 ·− and enhancing bilirubin reabsorption in the colon via enterohepatic cycling.

Association between elevated serum bilirubin levels with preserved lung function under conditions of exposure to air pollution

BackgroundHigh serum bilirubin levels have been shown to be associated with an improved pulmonary function test results. Their potential ability to similarly benefit pulmonary function in an environment of polluted air has not been tested. We retrospectively analyzed data of 15,605 apparently healthy individuals in order to evaluate the effect of serum bilirubin levels on forced expiratory volume in 1 s (FEV1).MethodsIndividuals attended the Tel-Aviv Medical Center Inflammatory Survey for a routine annual health check between February, 2002 and June, 2009 and were divided into low, medium and high serum bilirubin levels. Their FEV1 results were compared under various levels of air pollution. Air pollution and weather data were obtained from air pollution monitoring stations of the Israeli Ministry of Environmental Protection.ResultsThe elevated serum bilirubin concentrations on FEV1 were evaluated under moderate and high pollution levels FEV1 and were significantly higher in participants with high blood bilirubin levels compared to medium or low levels (p < 0.001 and p = 0.018, respectively). Participants with high levels of bilirubin had preserved FEV1 under exposure to high and medium pollution levels of both Nitrogen Oxide (NOx) and Carbon Monoxide (CO) pollutants (p = 0.003 and p = 0.022, respectively). The multivariate regression analysis revealed that the influence of bilirubin under conditions of air pollution remained significant even after adjustment for FEV1 confounders, but the interaction was not significant.ConclusionsElevated serum bilirubin concentrations are associated with preserved lung function in healthy individuals in Israel exposed to high levels of air pollution.

Inverse association between serum bilirubin level and testosterone deficiency in middle-aged and older men

Low serum bilirubin levels have been associated with increased risk of cardiovascular disease (CVD) and metabolic syndrome. Testosterone deficiency could also contribute to increased risk of CVD and metabolic syndrome. Therefore, this study aimed to examine the relationship between serum bilirubin level and testosterone deficiency in 1284 Korean men aged 45 to 70 years. Serum bilirubin level was categorized into quartiles: Q1 ≤ 0.7, Q2 0.8–0.9, Q3 1.0–1.1, and Q4 ≥ 1.2 mg/dL. Testosterone deficiency was defined as level less than 8.0 nmol/L, as suggested by the position statement of International Society of Andrology. The overall prevalence of testosterone deficiency was 5.8% and significantly decreased with the quartiles from Q1 to Q4. Compared with the referent fourth quartile (serum bilirubin ≥ 1.2 mg/dL), the ORs (95% CIs) for testosterone deficiency was 2.29 (1.04–4.94) for the first quartile after adjusting for age, fasting glucose, triglyceride, HDL-cholesterol, leukocyte count, hemoglobin, smoking status, and alcohol intake. We found inversely graded associations of serum bilirubin level with testosterone deficiency. These findings suggest that low bilirubin level may be interpreted as a state of testosterone deficiency in middle-aged and older men.

Comparison of Efficacy of Prophylactic versus Therapeutic Phototherapy in Preterm Neonates

Background: Jaundice neonatorum may predisposes preterm to develop bilirubin induced neurologic dysfunction even at lower total serum bilirubin level than term infant. Prophylactic phototherapy helps to maintain a lower serum bilirubin level may reduce the need for exchange transfusion in order to prevent kernicterus. Objective: To compare the efficacy of prophylactic versus therapeutic phototherapy among preterm neonates in reducing the frequency of exchange transfusion. Study Design: Randomized Controlled Trial. Settings: Neonatal Unit of Pediatrics department, Sir Ganga Ram Hospital Lahore-Pakistan. Duration: September 2018 to June 2019. Methodology: Two hundred preterm admitted in neonatal unit were enrolled and divided into 2 groups (A and B) using random numbers. Prophylactic phototherapy was initiated in Group A neonates within first 6 hours of life while it was applied when the serum bilirubin has reached to a pre-specified level in Group B. Daily total serum bilirubin level (also direct and indirect) was measured. Efficacy was measured in terms of preventing exchange transfusion. Data was entered and analyzed with SPSS version 21. Chi square was applied to compare efficacy between two groups with p ˂ 0.05 as significant. Results: Mean gestational age was 35.4 0.9 weeks in group A and 35.6 0.7 weeks in group B. There were 54% males and 46% females in group A while 51% males and 49% females in group B. The peak mean serum bilirubin level was observed on 3rd and 4th days in groups A and B respectively. Jaundiced neonates who received exchange transfusion in group A and B were 3% and 8% respectively (p=0.1209). Prophylactic phototherapy found efficacious in 97% preterm although, they received it for longer duration (147 34.25 vs 98 27.10 hours) (p 0.00001). Conclusion: Neonates received prophylactic phototherapy required less exchange transfusions compared to therapeutic group.

Association of serum bilirubin level with clinical outcomes after primary percutaneous intervention in patients with ST segment elevation myocardial infarction

Background Serum bilirubin (SB) increases acutely after ST segment elevation myocardial infarction (STEMI)/percutaneous coronary intervention (PCI), peaking at 21 h after the intervention. Aim The aim of this study is to investigate the association of SB levels with the prognosis of STEMI patients after 1ry PCI. Patients and methods This study was carried out on 90 patients admitted with STEMI and treated with 1ry PCI and were divided into three equal groups: group I included patients with high SB levels (≥0.7 mg/dl), group II included patients with intermediate SB levels (0.49–0.7 mg/dl) and group III included patients with low SB levels (≤0.49 mg/dl). Comparison of clinical results was performed in terms of major adverse cardiac events (MACE) during hospital admission. Results Patients with high SB had higher Killip class II–IV, higher hemoglobin and white blood cell count, lower HDL levels, lower ejection fraction (EF) and higher rate of death and congestive heart failure. No significant difference was found in age, sex, family history of coronary artery disease (CAD), history of HTN, diabetes mellitus or smoking, dyslipidemia, symptoms duration, time to reperfusion, random blood sugar on admission, STEMI location, infarction-related artery, number of diseased vessels, type of intervention, Thrombolysis in Myocardial Infarction (TIMI) flow, serum triglycerides and LDL level, serum creatinine and Creatinine Kinase - MB (CK-MB) level on admission, number of patients undergoing reinfection and target vessel revascularization. High SB levels predicted the overall MACE following STEMI. Conclusion High SB was accompanied by in-hospital cardiac mortality, advanced heart failure and MACE after 1ry PCI in STEMI patients.

Serum bilirubin level is a strong predictor for disability in activities in daily living (ADL) in Japanese elderly patients with diabetes

Elderly patients with diabetes are at increased risk of frailty and disability in activities of daily living (ADL). Recent evidence has shown that oxidative stress is associated with these conditions. In this cross-sectional study, we aimed to assess whether serum level of bilirubin, a strong endogenous antioxidant, can predict ADL disability in elderly patients with diabetes. Forty elderly patients aged 70 years and older with diabetes and ADL disability and 158 elderly patients with diabetes and without ADL disability were continuously recruited. Multivariate logistic regression models showed that serum bilirubin level was a significant predictor for ADL disability. Receiver operating characteristic analysis showed that the area under the curve (AUC) of serum bilirubin level alone for ADL disability was 0.887 (95% CI 0.837–0.936, P < 0.001) and the cut-off value was 0.4 mg/dL (sensitivity = 88.0% and specificity = 65.0%). The predictive ability was further increased by the addition of age (AUC = 0.921) or addition of age, body mass index, red blood cell count, cerebrovascular disease and chronic renal failure (AUC = 0.953). In conclusion, low serum bilirubin level is a strong predictive biomarker for ADL disability in elderly patients with diabetes, and its clinical utility is suggested.

Low serum bilirubin, albumin, and uric acid levels in patients with Crohn's disease.

Serum concentrations of bilirubin, albumin, and uric acid (UA) play important roles in controlling oxidative stress. Until now, there are few researches related to the relationship between oxidative stress and Crohn's disease (CD); furthermore, no such study has been reported from China. Our aim was to evaluate serum bilirubin, albumin, and UA levels in CD patients and relate them to disease activity.Seventy-one patients diagnosed with CD and 125 sex- and age-matched healthy individuals were retrospectively analyzed during the same period. Clinical characteristics and laboratory parameters were analyzed in CD patients and healthy control groups.Serum levels of bilirubin, albumin, and UA in patients with CD were significantly lower than those in the healthy control group. Correlation analysis demonstrated that serum concentrations of total bilirubin, direct bilirubin, indirect bilirubin, albumin, and UA were negatively related to disease activity in patients with CD (r = −0.620, P < .001; r = −0.304, P < .05; r = −0.623, P < .001; r = −0.408, P < .01; and r = −0.296, P < .05; respectively).Serum bilirubin, albumin and UA levels were significantly lower in CD patients, suggesting potential correlations between serum bilirubin, albumin, and UA levels and disease activity in CD patients. In addition, the noninvasive biochemical index may be potential markers for assessing the disease activity of patients with CD.

A study on serum bilirubin levels in coronary artery disease patients

Background: The protective effect of bilirubin relates to the antioxidant property of bilirubin, which prevents lipid oxidation, especially low-density lipoprotein (LDL), and inhibits free radical-induced dam-ages. Lower serum bilirubin level has been proven to be associated with endothelium and microvascular malfunction. The aim of the present study was to assess the association between serum bilirubin levels and coronary artery disease in comparison with controls without coronary artery disease.Methods: A cross-sectional study was conducted for a period of a one year in our medical college hospital. Patients with evidence of coronary artery disease for not more than 10 years of duration confirmed by ECG, ECHO and other previous case records were taken as cases. Controls were selected matched with age, gender and other co-morbid conditions. Total of 200 subjects were included in the study with 100 cases and 100 controls. General and systemic examination was conducted on all study subjects including laboratory investigations like complete blood count, renal function test, lipid profile, viral markers such as HBsAG, HCVIgM and liver function test which includes total bilirubin, direct and indirect, liver enzymes, albumin and globulin levels. A 12 lead ECG and a transthoracic echocardiogram was performed for all patients.Results: The various liver function test parameters were compared between the cases and controls it was found that the serum bilirubin levels which includes total bilirubin, direct bilirubin and indirect bilirubin was found to be lower among the case group compared to the control group and this difference was found to be statistically significant (p &lt;0.05). A perfect linear correlation between the ejection fraction and serum bilirubin levels, as the ejection fraction decreases the serum bilirubin levels was also decreasing.Conclusions: This study showed a significant association between the reduced serum bilirubin levels and the occurrence of CAD; therefore, bilirubin level can serve as a predictive factor, together with other influential factors for identifying a person at risk of developing coronary artery disease.

Low serum bilirubin levels associated with subclinical atherosclerosis in patients with obstructive sleep apnea

BackgroundObstructive sleep apnea (OSA) is a chronic, progressive disease that can cause cardiovascular complications and atherosclerosis. We evaluated the relationship between serum bilirubin levels and carotid intima-media thickness (cIMT), as a surrogate marker of subclinical atherosclerosis, in patients with OSA.MethodsWe enrolled 84 consecutive patients with OSA. The patients underwent ultrasonography, polysomnography, and echocardiography. Blood samples were obtained from all of the subjects, which were used for biochemical comparisons. The patients were divided into groups according to cIMT values (<0.9 vs. >0.9 mm).ResultsThe patient population consisted of 84 OSA patients (mean age: 54.2 + 8.0 years, 62.9% male). The OSA patients with cIMT ≥0.9 had significantly elevated high-sensitive C-reactive protein (hsCRP), Oxygen desaturation index, apnea–hypopnea index (AHI), and significantly lower total and indirect bilirubin levels. Multivariate regression analyses revealed that total bilirubin, hsCRP, and AHI were the independent predictors of subclinical atherosclerosis. There was a negative correlation between total bilirubin and cIMT.ConclusionsThis study showed that high hsCRP and low serum total bilirubin levels could be paving the way for the development of subclinical atherosclerosis. Simple measures such as total bilirubin may provide predictive information regarding the risk of cardiovascular disease in patients with OSA.

Levels of serum bilirubin in small cell lung cancer and non-small cell lung cancer patients

Elevated bilirubin has been associated with protection of cardiovascular and kidney systems, whereas decreased bilirubin may predispose respiratory diseases. However, whether serum bilirubin levels are associated with lung cancer remains unclear. Here, clinical and pathologic data of a cohort of 363 lung cancer patients along with 363 age-and gender-matched healthy subjects were collected. The association of serum bilirubin levels with lung cancer was analyzed. The levels of serum bilirubin were significantly lower in lung cancer patients. The aspartate transaminase and alkaline phosphatase levels were significantly higher in lung cancer. Multi-classification logistics regression analysis revealed low total bilirubin level [OR (95%CI), 1.12 (1.02-1.23)], aspartate transaminase [OR (95%CI), 1.12 (1.02-1.23)], and alanine transaminase [OR (95%CI), 1.12 (1.02-1.23)] were risk factors in lung cancer. Serum bilirubin levels were significantly changed among small cell lung cancer (SCLC), lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSC). Total bilirubin level, smoke history and heart disease were risk factors for subtypes. Compared with LSC, patients with smoke history had significant higher risk in LAC [OR (95% Confidence Interval, CI), 4.49 (1.70, 11.96)]. Compared with LSC, patients with smoke history [OR (95%CI), 4.49 (1.70, 11.96)] and heart disease [OR (95%CI), 4.49 (1.70, 11.96)] had significant higher risk in SCLC. Compared with SCLC, patients with low total bilirubin [OR (95%CI), 1.12 (1.02-1.23)] and heart disease [OR (95%CI), 3.52 (1.01-12.23)] had significant higher risk in LAC. Taken together, these results suggested low serum bilirubin levels are tightly associated with lung cancer, especially with LAC. Serum bilirubin levels might serve as a predictor for lung cancer patients clinically.

Low serum bilirubin levels contribute to the presence and progression of distal symmetrical polyneuropathy in Chinese patients with type 2 diabetes

AimTo investigate the association between serum bilirubin and distal symmetrical polyneuropathy (DSPN) in Chinese patients with type 2 diabetes (T2D). MethodsA total of 1800 inpatients with T2D (including 68 with 1-year follow-ups) were consecutively enrolled between June 2014 and March 2017. DSPN was diagnosed according to criteria recommended by the Toronto Diabetic Neuropathy Expert Group in 2010. Clinical data were retrospectively collected. ResultsPatients with vs. without DSPN had low levels of serum total bilirubin (9.9±3.1μmol/L vs. 10.7±2.8μmol/L; P<0.01) and unconjugated bilirubin (6.7±2.2μmol/L vs. 7.3±2.1μmol/L; P<0.01), respectively. Patients in the lowest tertiles of bilirubin had the highest rates of DSPN and slowest nerve conduction velocities (NCVs). After multivariate adjustment, low levels of unconjugated bilirubin were a risk factor (OR: 0.696, 95% CI: 0.494–0.981; P=0.038, highest vs. lowest) for the presence of DSPN. Furthermore, in the 68 patients who had 1-year follow-ups, those with the lowest tertiles of serum bilirubin showed maximum deterioration in NCVs. These changes remained significant even after multivariate adjustment. ConclusionLow levels of serum bilirubin, especially unconjugated bilirubin, contributed to the presence and progression of DSPN in Chinese patients with T2D. Thus, serum unconjugated bilirubin may be used as an additional indicator of risk and progression of DSPN.