Association Of Serum Bilirubin Levels Research Articles

Association of serum bilirubin levels and glycemic measurements in Type 2 diabetic patients

Introduction: Bilirubin, a waste product of the heme catabolic pathway, has proven to be a natural antioxidant associated with a lower prevalence of oxidative stress-mediated diseases. This study evaluates the association of serum bilirubin levels with Glycated Hemoglobin (HbA1c), Fasting Blood Sugar (FBS) and Post Prandial Blood Sugar (PPBS) in diabetic patients. Methods: A retrospective analytical study was conducted at the Department of Haematology of the Sri Jayewardenepura General Hospital. Data was obtained through a laboratory information system of randomly selected 201 adult patients diagnosed with T2DM and grouped as poorly and well controlled using HbA1c values over and below 7%, respectively. Normal ranges for serum bilirubin, FBS, and PPBS were (0.3-1.2) mg/dL, (75-110) mg/dL and (80-140) mg/dL, respectively. Data were analyzed using (SPSS) version 20, descriptive statistical methods, Pearson’s Correlation test and independent sample t-test. P<0.05 was considered significant. Results: A negative correlation between total bilirubin and HbA1c (r = -0.234, p=0.001) was observed. There was no statistically significant correlation between total bilirubin level and FBS (p=0.131), PPBS (p=0.408), and age (p=0147). However, the mean values of total bilirubin (p=0.001), FBS (p<0.001) and PPBS (p<0.001) were significant between diabetes well controlled and poorly controlled groups. A statistically positive correlation was observed between HbA1c and FBS (p<0.001) and PPBS (p<0.001), but not with age (p=0.887). Conclusion: There was a significant relationship between total bilirubin with FBS, and PPBS in both groups. A significant negative correlation was found between total bilirubin and HbA1c, suggesting a potential protective or modulatory role of bilirubin in glycemic control. No significant correlation was observed between total bilirubin levels and FBS, PPBS, or age in the total population.Keywords: T2DM, HbA1c, bilirubin, FBS, PPBS

Association of Serum Bilirubin Levels with Macro- and Microvascular Complications in Chinese People with Type 2 Diabetes Mellitus: New Insight on Gender Differences.

Previous studies suggested protective effects of bilirubin against cardiovascular disease, with a possible gender difference. However, the relationship between serum total bilirubin (TBIL) with diabetic macro- and microvascular complications remains unknown. We aimed to examine the association of macro- and microvascular complications with serum TBIL levels. Serum TBIL was measured in 648 patients with T2DM. Demographic and clinical data were obtained from the inpatient medical record system. Serum TBIL was measured with an automatic biochemistry analyzer according to routine protocols. Parameters of vascular complications, including ankle-brachial index, carotid intima-media thickness, estimated glomerular filtration rate and the urinary albumin to creatinine ratio, were measured and calculated. The association between TBIL and diabetic macro- and microvascular complications was analyzed. In multivariable logistic regression, after adjustment for age, sex, body mass index and diabetic duration, higher serum TBIL levels were significantly associated with decreased odds of microalbuminuria (OR = 0.31, [95% CI] 0.16-0.61, P = 0.003) and chronic kidney disease (OR = 0.19, [95% CI] 0.09-0.41, P < 0.001). These associations were only found in male but not in female patients. However, no significant relationship was found between TBIL and peripheral arterial disease or carotid hypertrophy. Our findings suggest that physiological higher TBIL level might be a protective factor for diabetic microvascular complications.

Association of serum total bilirubin levels with progressive renal decline and end-stage kidney disease: 10-year observational cohort study in Japanese patients with diabetes.

ObjectivePrevious reports have demonstrated the association of serum bilirubin levels with the progression of diabetic nephropathy. The objective of this study is to assess the association of basal bilirubin levels with progressive renal decline (PRD) and end-stage kidney disease (ESKD).MethodsA total of 298 patients with diabetes who visited Kyushu University Hospital (Japan) were recruited and followed up for 10 years. PRD was defined as a negative change in estimated glomerular filtration ratio (eGFR) >3.7%/year, 2.5th percentile. Logistic regression analysis was performed to evaluate the association of total bilirubin levels with PRD and its cut-off point was determined by receiver operating characteristic (ROC) analysis. Kaplan-Meier method and Cox hazard regression analysis were used to evaluate the predictive ability of its cut-off point for ESKD.ResultsLogistic regression model showed that total bilirubin levels were significantly associated with PRD, and ROC analysis showed that its cut-off point was 0.5 mg/dL. Kaplan-Meier method showed that the percent of patients who reached two endpoints, composite endpoint (ESKD or doubling of creatinine level) or 30% eGFR decline, was significantly higher in the low bilirubin group than in the high bilirubin group (18.5% vs 11.0%, P = 0.045; 49.1% vs 42.1%, P = 0.045, respectively, log-rank test). Cox hazard regression models confirmed the independence of the predictive ability of its cut-off point.ConclusionsSerum total bilirubin levels were negatively associated with PRD in diabetic nephropathy and its cut-off point was 0.5 mg/dL. It may be clinically useful for identifying patients at high risk of ESKD.

Association of serum bilirubin levels with risk of cancer development and total death

Serum levels of bilirubin, a strong antioxidant, may influence cancer risk. We aimed to assess the association between serum bilirubin levels and cancer risk. Data were retrieved from 10-year electronic medical records at Kyushu University Hospital (Japan) for patients aged 20 to 69 years old. The associations of baseline bilirubin levels with cancer risk (lung, colon, breast, prostate, and cervical) were evaluated using a gradient boosting decision tree (GBDT) model, a machine learning algorithm, and Cox proportional hazard regression model, adjusted for age, smoking, body mass index, and diabetes. The number of study subjects was 29,080. Median follow-up time was 4.7 years. GBDT models illustrated that baseline bilirubin levels were negatively and non-linearly associated with the risk of lung (men), colon, and cervical cancer. In contrast, a U-shaped association was observed for breast and prostate cancer. Cox hazard regression analyses confirmed that baseline bilirubin levels (< 1.2 mg/dL) were negatively associated with lung cancer risk in men (HR = 0.474, 95% CI 0.271–0.828, P = 0.009) and cervical cancer risk (HR = 0.365, 95% CI 0.136–0.977, P = 0.045). Additionally, low bilirubin levels (< 0.6 mg/dL) were associated with total death (HR = 1.744, 95% CI 1.369–2.222, P < 0.001). Serum bilirubin may have a beneficial effect on the risk of some types of cancers.

Serum bilirubin level is associated with exercise capacity and quality of life in chronic obstructive pulmonary disease

BackgroundBilirubin has antioxidant properties against chronic respiratory diseases. However, previous studies are limited by acquisition of serum bilirubin level at one time point and its analysis with clinical parameters. We evaluated the association of serum bilirubin levels with various clinical outcomes of chronic obstructive pulmonary disease (COPD) in Korean Obstructive Lung Disease (KOLD) cohort.MethodsWe included 535 patients with COPD from the KOLD cohort. Serum bilirubin levels and various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life (QoL), and exacerbation, were evaluated annually; their association was analyzed using generalized estimating equations and the linear mixed model.ResultsAmong 535 patients, 345 (64.5%) and 190 (35.5%) were categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II and GOLD III-IV groups, respectively. 6 MW distance was positively associated with serum bilirubin levels, especially in the GOLD I-II group (estimated mean = 41.5). Among QoL indexes, the COPD assessment test score was negatively associated with serum bilirubin levels only in the GOLD I-II group (estimated mean = − 2.8). Higher serum bilirubin levels were independently associated with a higher number of acute exacerbation in the GOLD III-IV group (estimated mean = 0.45, P = 0.001). Multivariate analysis revealed that lung function and mortality were not associated with serum bilirubin levels.ConclusionsHigher serum bilirubin levels were associated with a longer 6 MW distance and better QoL, especially in the GOLD I-II group, whereas they were related to a higher risk of acute exacerbation, especially in the GOLD III-IV group. Bilirubin levels may represent various conditions in COPD.

The role of serum bilirubin levels in determining venous thromboembolism

ObjectiveVenous thromboembolism (VTE) is a disease that includes both deep venous thrombosis (DVT) and pulmonary embolism (PE). Bilirubin is an endogenous anti-inflammatory marker associated with atherothrombosis. The purpose of our study was to investigate the association of serum bilirubin levels with the presence of VTE. MethodsA total of 103 patients with VTE (distal DVT, n = 34; proximal DVT, n = 30; PE, n = 39) and 50 control patients were cross-sectionally enrolled. Peripheral venous duplex ultrasound and computed tomography were used for the diagnosis of VTE. Fasting blood samples were drawn for biochemical analyses. ResultsBaseline characteristics were not different between groups. The VTE group had lower bilirubin level (9.0 ± 2.6 μmol/L vs 7.3 ± 3 μmol/L; P = .001) and higher high-sensitivity C-reactive protein (hs-CRP) concentration (0.8 [0.3-2] mg/L vs 1.1 [0.2-3] mg/L; P = .008) and white blood cell count (7.4 ± 1.5 × 109/L vs 8.2 ± 2.7 × 109/L; P = .02) compared with control patients. In the analysis of variance, the levels of total direct bilirubin and hs-CRP were clearly different between the control group and VTE subgroups (distal and proximal DVT and PE). The receiver operating characteristic curve analysis showed a cutoff value of 8.9 μmol/L for total bilirubin (sensitivity, 74%; specificity, 55%) and an area under the curve of 0.659 (P < .001). ConclusionsBilirubin level, hs-CRP concentration, and white blood cell count were independently associated with VTE.

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.

Association of serum bilirubin with renal outcomes in Han Chinese patients with chronic kidney disease

BackgroundOxidative stress and inflammation play pivotal roles in chronic kidney disease (CKD). Bilirubin is an endogenous anti-inflammatory antioxidant. However, the relationship between serum bilirubin and renal outcomes in CKD is controversial. We explored the association of serum bilirubin levels with renal outcomes in Han Chinese patients with CKD. MethodsClinical and laboratory data were collected from 316 patients with CKD. The primary clinical endpoint was renal replacement therapy or death. The association between serum bilirubin and clinical parameters was assessed by correlation analysis. Multiple Cox regression analysis was used to explore the relationship between serum bilirubin and renal outcomes in patients with CKD. ResultsSerum total and indirect bilirubin were positively correlated with estimated glomerular filtration rate, but negatively correlated with 24-h urine protein in patients with CKD. Serum total and indirect bilirubin were inversely associated with CKD stages in patients with CKD stages 1–5. Multiple Cox regression analysis demonstrated that the higher concentration of serum total bilirubin was independently associated with better renal outcomes in CKD. ConclusionsOur results suggest that serum total bilirubin may have protective effects on kidneys.

Association of serum bilirubin levels with mortality in patients with diabetes initiating chronic hemodialysis: a competing risks analysis of a single-center cohort

Evidence remains scarce regarding the property of serum bilirubin levels as a prognostic factor for the incidence of mortality in dialysis patients. Here, we aimed to examine the association between serum bilirubin levels and mortality in patients with diabetes initiating hemodialysis. This was a single-center, observational, historical cohort study of 395 Japanese patients with diabetes initiating chronic hemodialysis. There were 98 women and 297 men, and the mean (±SD) age was 61 ± 12 years. Patients were dichotomized at the baseline median level of serum bilirubin (0.3 mg/dL). The endpoints were the incidence of all-cause and cause-specific mortality. Hazard ratios for these endpoints were estimated using the Fine-Gray subdistribution hazard model and cause-specific hazard model because of the presence of competing risks. During a median follow-up period of 3.9 years (range; 0.0–10.7 years), there were 83 cases of death, consisting of 39 and 44 cases from atherosclerotic cardiovascular diseases (ASCVDs) and non-ASCVDs, respectively. In the multivariate competing risks analysis, patients with lower bilirubin levels were associated with higher risk of ASCVD-related mortality (subdistribution hazard ratio 3.57, p = 0.015) but not with non-ASCVD-related mortality (0.83, p = 0.665) than those with higher bilirubin levels. Analysis treating bilirubin levels as a continuous variable, as well as cause-specific models yielded the similar results. Lower serum levels of bilirubin may be predictive of higher risk of ASCVD-related mortality in patients with diabetes initiating chronic hemodialysis. There was no relationship between levels of bilirubin and non-ASCVD-related mortality.

PW209 Association of serum bilirubin levels and promoter variations of HMOX1 and UGT1A1 genes with fabry disease

PW209 Association of serum bilirubin levels and promoter variations of HMOX1 and UGT1A1 genes with fabry disease

Association of serum bilirubin levels with development and progression of albuminuria, and decline in estimated glomerular filtration rate in patients with type2 diabetes mellitus.

Recent observational studies suggest elevated levels of bilirubin, an endogenous anti-oxidant, might protect against kidney disease. We carried out an observational cohort study to assess whether higher baseline levels of bilirubin, within normal range, could predict the rate of development and progression of diabetic nephropathy in patients with type2 diabetes. Japanese type2 diabetic patients with normo- or microalbuminuria and normal serum bilirubin (<1.2mg/dL) were recruited from a single center, and categorized according to baseline serum bilirubin levels. Two independent end-points were specified: development or progression of diabetic nephropathy, based on transition to a more advanced stage of albuminuria (albuminuria cohort), and the rate of change in estimated glomerular filtration rate (eGFR cohort). Albuminuria and eGFR cohorts were constructed consisting of 1,915 patients and 1,898 patients, respectively, with 1,738 patients overlapping. Mean follow up was 4.4 and 5.4years for the two cohorts, respectively. Within the albuminuria cohort, 132 (9%) of 1,418 patients with normoalbuminuria developed microalbuminuria, and 56 (11%) of 497 patients with microalbuminuria developed macroalbuminuria. Higher baseline bilirubin levels were associated with significantly lower risk of progression from microalbuminuria to macroalbuminuria in both the univariate and multivariate analyses. In normoalbuminuric patients, an inverse association was found when restricted to a subgroup with elevated hemoglobin A1c levels. There was no relationship between bilirubin levels and the rate of change in eGFR. Higher serum bilirubin levels, within normal range, might be predictive of a lower risk of progression of nephropathy in type2 diabetic patients.

The Association of Serum Bilirubin Levels on the Outcomes of Severe Sepsis

Admission serum bilirubin levels have been incorporated into severity of illness scoring systems in critical illness as a marker of liver dysfunction. The purpose of our study is to determine the independent association of serum bilirubin with mortality in severe sepsis and septic shock. We conducted a retrospective study of adult patients admitted with severe sepsis and septic shock. We excluded patients with a prior history of liver disease. We identified the highest serum bilirubin within 72 hours of admission and stratified bilirubin levels into ≤1 mg/dL (normal), 1.1 to 2 mg/dL (abnormal up to 2 mg/dL), and >2 mg/dL. We sought to determine the independent association of hyperbilirubinemia with mortality and length of intensive care unit stay in persons with severe sepsis and septic shock. A total of 251 patients met criteria for severe sepsis. In all, 200 patients had a bilirubin of <1 mg/dL, and 51 had a bilirubin of >1 mg/dL. Of these 51, 12 had a bilirubin >2 mg/dL. Mortality was 12%, 24%, and 42% in persons with a bilirubin ≤1, 1.1 to 2, and >2 mg/dL, respectively. Compared to those with a bilirubin ≤ 1 mg/dL, adjusted odds of mortality in patients were 3.85 (95% confidence interval [CI] 1.21-12.2) and 9.85 (95% CI 1.92-50.5) times higher in persons with bilirubin levels between 1.1 and 2 and >2 mg/dL, respectively. After multivariable adjustment for potential confounding factors, elevated serum bilirubin levels within 72 hours of admission are associated with an increased risk of mortality in patients with severe sepsis and septic shock. Prospective studies are warranted to further validate our findings.

Serum bilirubin levels are lower in overweight asymptomatic middle-aged adults: An early indicator of metabolic syndrome?

ObjectiveLow levels of bilirubin have recently been associated with obesity, diabetes mellitus, and metabolic syndrome. Here, we hypothesized that serum bilirubin levels might be already altered in overweight asymptomatic middle-aged individuals before full development of the metabolic syndrome. MethodsHealthy nonsmoking adults aged 25–49 (64 women and 32 men) participated in this cross-sectional study. All participants who reported stable weight within the last three months underwent standard anthropomorphological measurements of body composition, blood pressure measurements, aerobic and anaerobic capabilities assessment, dietary intake evaluation, and fasting serological measurements of total and direct bilirubin, glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive protein. Participants were divided into normal-weight and overweight groups. Linear correlation and multiple regression analyses were used to examine the association of serum bilirubin levels with all metabolic syndrome risk factor changes. ResultsSerum bilirubin levels were lower in overweight healthy individuals of both sexes, and were negatively associated with abdominal obesity, insulin resistance, fasting glucose, fasting insulin, fasting triglycerides, total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein levels but positively associated with aerobic body capabilities. ConclusionOur findings suggest that serum bilirubin levels have the potential to be employed as an early biomarker for indicating asymptomatic individuals at increased risk of developing metabolic syndrome.

Association of Serum Bilirubin with Stroke Severity and Clinical Outcomes

The aim of the study is to explore the association of serum bilirubin levels with admission severity and short term clinical outcomes among acute ischemic stroke patients. Data were collected from 2361 acute ischemic stroke patients in four hospitals of Shangdong Province during January 2006 and December 2008. National Institutes of Health Stroke Scale (NIHSS) was used to assess admission and discharge severity. NIHSS≥10 at discharge or in-hospital death was defined as short-term clinical outcomes. Logistic regression and trend test were used to examine the association of serum bilirubin levels with admission severity and short term clinical outcomes. Serum bilirubin levels were significantly and positively associated with admission severity (P for trend <0.05). The age-sex adjusted odds ratios (95% confidential intervals) of NIHSS≥10 associated with the second, third and fourth quartile of total bilirubin/direct bilirubin were 1.245 (0.873, 1.777)/1.276 (0.895, 1.818), 1.484 (1.048, 2.102)/1.628 (1.158, 2.289) and 2.869 (2.076, 3.966)/2.765 (1.996, 3.828), respectively, compared with the lowest quartile; the multivariate adjusted odds ratios of NIHSS≥10 associated with the second, third and fourth quartile of total bilirubin/direct bilirubin were 1.088(0.711, 1.665)/1.436(0.94, 2.193), 1.328(0.877, 2.011)/1.647(1.092, 2.485) and 2.336(1.579, 3.458)/3.079 (2.049, 4.623), respectively, compared with the lowest quartile. However, no association between serum bilirubin levels and short-term clinical outcomes was observed in our study. Serum bilirubin levels were associated with initial stroke severity closely. Nevertheless, there is no significant relationship between serum bilirubin levels and short-term clinical outcomes among acute ischemic stroke patients.

Association between bilirubin and cardiovascular disease risk factors: using Mendelian randomization to assess causal inference

BackgroundElevated serum bilirubin has been associated with reduced risk of cardiovascular disease (CVD). However, serum bilirubin is also related with several potential confounders related to CVD, such as obesity. Mendelian randomization has been proposed as a method to address challenges to validity from confounding and reverse causality. It utilizes genotype to estimate causal relationships between a gene product and physiological outcomes. In this report, we demonstrate its use in assessing direct causal relations between serum bilirubin levels and CVD risk factors, including obesity, cholesterol, measures of vascular function and blood pressure.MethodsStudy subjects included 868 asymptomatic individuals. Study subjects were genotyped at the UGT1A1*28 locus, which is strongly associated with bilirubin levels.ResultsSerum bilirubin levels were inversely associated with levels of several cardiovascular disease risk factors, including body mass index (p = 0.003), LDL (p = 0.0005) and total cholesterol (p = 0.0002). In contrast, UGT1A1*28 genotype, a known cause of elevated bilirubin levels, was not significantly associated with any of these traditional CVD risk factors. We did observe an association between genotype and brachial artery diameter (p = 0.003) and cold pressor reactivity (p = 0.01).ConclusionsOur findings imply that the observed association of serum bilirubin levels with body mass index and cholesterol are likely due to confounding and suggest that previously established CVD benefits of increased bilirubin may in part be mediated by the early regulation of vascular structure and reactivity.

Association of serum bilirubin levels with albuminuria in patients with essential hypertension

Objectives This study was undertaken to evaluate the relationship between serum bilirubin concentrations and the degree of urinary albumin excretion in hypertensive patients. Design and methods A total of 120 hypertensive subjects were enrolled, in which 80 (67%) with normoalbuminuria (albumin excretion rate [AER] of < 20 μg/min), 30 (25%) with microalbuminuria (AER of 20–200 μg/min) and 10 (8%) with macroalbuminuria (AER > 200 μg/min). Logarithmic (log) transformation of urinary albumin excretion was carried out before performing correlation and regression analysis. Results Patients with micro- or macroalbuminuria had significantly lower serum bilirubin concentrations ( P = 0.004). By multivariate regression analysis, serum bilirubin concentration was an independent determinant of albuminuria and had an inverse correlation with log (urinary albumin excretion) in hypertensive patients ( β = − 0.189, P = 0.023). Conclusions These findings may partly explain the pathogenetic processes that link microalbuminuria and enhanced cardiovascular risk in hypertensive patients.

Serum bilirubin levels and mortality after myeloablative allogeneic hematopoietic cell transplantation†

Many patients who undergo hematopoietic cell transplantation experience liver injury. We examined the association of serum bilirubin levels with nonrelapse mortality by day +200, testing the hypothesis that the duration of jaundice up to a given point in time provides more prognostic information than either the maximum bilirubin value or the value at that point in time. We studied 1,419 consecutive patients transplanted from allogeneic donors. Total serum bilirubin values up to day +100, death, or relapse were retrieved-along with nonrelapse mortality by day +200 as an outcome measure--using Cox regression models with each bilirubin measure modeled as a time-dependent covariate. The bilirubin value at a particular point in time provided the best fit to the model for mortality. With bilirubin at a point in time modeled as an 8th-degree polynomial, an increase in bilirubin from 1 to 3 mg/dL is associated with a mortality hazard ratio of 6.42. An increase from 4 to 6 mg/dL yields a hazard ratio of 2.05, and an increase from 10 to 12 mg/dL yields a hazard ratio of 1.17. Among patients who were deeply jaundiced, survival was related to the absence of multiorgan failure and to higher platelet counts. In conclusion, the value of total serum bilirubin at a particular point in time after transplant carries more informative prognostic information than does the maximum or average value up to that point in time. The increase in mortality for a given increase in bilirubin value is larger when the starting value is lower.