Relationship between Serum Indirect Bilirubin Level and Insulin Sensitivity: Results from Two Independent Cohorts of Obese Patients with Impaired Glucose Regulation and Type 2 Diabetes Mellitus in China

Zhang, Fan; Guan, Wei; Fu, Zhen-Yan; Zhou, Li; Guo, Wen; Ma, Yi-Ping; Gong, Yingyun; Jiang, Wanzi; Liang, Hui; Zhou, Hongwen

doi:10.1155/2020/5681296

Cited by 17 publications

(15 citation statements)

References 43 publications

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“…Diabetic patients are often characterized by more complex, extensive, and diffuse coronary lesions. As introduced in the beginning, abnormal bilirubin levels were observed in the diabetic patients (16,17). Together with our studies, DB was a surrogate biomarker of oxidative and inflammatory responses, the common mechanisms in both ACS and diabetes.…”

Section: Resultssupporting

confidence: 74%

“…Oxidative stress exerts a great impact on insulin resistance, which raises a question on whether bilirubin plays a role in this pathway (15). A study in obese patients with type 2 diabetes found that bilirubin acted as a protective factor in insulin resistance (OR = 0.744, 95% CI: 0.590-0.938, p = 0.012) (16). Nevertheless, an interesting result was also observed in that TB, DB, and indirect bilirubin levels were higher in the diabetes group than in the normal metabolism population.…”

Section: Introductionmentioning

confidence: 94%

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Direct Bilirubin Levels Predict Long-Term Outcomes in Patients With Acute Coronary Syndrome Under Different Glucose Metabolism Status: A 6.5-Year Cohort Study of Three-Vessel Disease

Liu

Zhang

Jiang

et al. 2021

Front. Cardiovasc. Med.

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Background: There is controversy over the relationship between bilirubin and coronary artery disease. This study aimed to evaluate the predictive value of direct bilirubin (DB) in patients with complex acute coronary syndrome (ACS).Methods: From April 2004 to February 2011, 5,322 ACS patients presenting with three-vessel disease were consecutively enrolled. Disease severity and complexity were determined by SYNTAX score (SS) and SS II. The primary endpoint was all-cause death, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE). Stratification of normal glucose regulation, prediabetes, and diabetes was based on a previous diagnosis, hypoglycemic medications, fasting blood glucose, and hemoglobin A1c.Results: Subjects were divided into quartiles according to baseline DB (μmol/L): Q1 (0–1.6), Q2 (1.61–2.20), Q3 (2.21–2.80), and Q4 (>2.80). Multivariable logistic regression analysis showed that DB was an independent predictor of intermediate–high SS. During a median follow-up time of 6.5 years, elevated DB was associated with more all-cause death (p < 0.001) but not MACCE. DB remained to be predictive of all-cause death in the multivariable Cox regression model (Q2 vs. Q1: HR 1.043, 95% CI 0.829–1.312, p = 0.719; Q3 vs. Q1: HR 1.248, 95% CI 1.001–1.155, p = 0.048; Q4 vs. Q1: HR 1.312, 95% CI 1.063–1.620, p = 0.011). When subjects are stratified according to glucose metabolism regulation and treatment strategies, the predictivity of DB was only profound in patients with diabetes or with conservative treatment. Additionally, incorporating DB further improved the discrimination and reclassification abilities of SS II for risk prediction.Conclusion: DB is a potential biomarker for predicting lesion severity and long-term outcomes in ACS patients.

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Section: Resultssupporting

confidence: 74%

Section: Introductionmentioning

confidence: 94%

Direct Bilirubin Levels Predict Long-Term Outcomes in Patients With Acute Coronary Syndrome Under Different Glucose Metabolism Status: A 6.5-Year Cohort Study of Three-Vessel Disease

Liu

Zhang

Jiang

et al. 2021

Front. Cardiovasc. Med.

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“…The serum total bilirubin concentrations in the present study were inversely associated with the insulin resistance risk. Previous studies also reported that serum total bilirubin concentrations are inversely related to the MetS risk in various ethnic groups [ 43 , 44 , 45 , 46 ]. It might be associated with the cholesterol metabolism in the liver.…”

Section: Discussionmentioning

confidence: 86%

Development and Validation of an Insulin Resistance Predicting Model Using a Machine-Learning Approach in a Population-Based Cohort in Korea

Park

Kim

2022

Diagnostics

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Background: Insulin resistance is a common etiology of metabolic syndrome, but receiver operating characteristic (ROC) curve analysis shows a weak association in Koreans. Using a machine learning (ML) approach, we aimed to generate the best model for predicting insulin resistance in Korean adults aged > 40 of the Ansan/Ansung cohort using a machine learning (ML) approach. Methods: The demographic, anthropometric, biochemical, genetic, nutrient, and lifestyle variables of 8842 participants were included. The polygenetic risk scores (PRS) generated by a genome-wide association study were added to represent the genetic impact of insulin resistance. They were divided randomly into the training (n = 7037) and test (n = 1769) sets. Potentially important features were selected in the highest area under the curve (AUC) of the ROC curve from 99 features using seven different ML algorithms. The AUC target was ≥0.85 for the best prediction of insulin resistance with the lowest number of features. Results: The cutoff of insulin resistance defined with HOMA-IR was 2.31 using logistic regression before conducting ML. XGBoost and logistic regression algorithms generated the highest AUC (0.86) of the prediction models using 99 features, while the random forest algorithm generated a model with 0.82 AUC. These models showed high accuracy and k-fold values (>0.85). The prediction model containing 15 features had the highest AUC of the ROC curve in XGBoost and random forest algorithms. PRS was one of 15 features. The final prediction models for insulin resistance were generated with the same nine features in the XGBoost (AUC = 0.86), random forest (AUC = 0.84), and artificial neural network (AUC = 0.86) algorithms. The model included the fasting serum glucose, ALT, total bilirubin, HDL concentrations, waist circumference, body fat, pulse, season to enroll in the study, and gender. Conclusion: The liver function, regular pulse checking, and seasonal variation in addition to metabolic syndrome components should be considered to predict insulin resistance in Koreans aged over 40 years.

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“…However, these associations were weak and of doubtful clinical relevance. An inverse association between serum bilirubin and HOMA-IR has been, nonetheless, previously reported in adults and children [57,58].…”

Section: Discussionmentioning

confidence: 95%

Association of Serum Bilirubin Level with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study of 1672 Obese Children

Bellarosa

Bedogni

Bianco

et al. 2021

JCM

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As in adults, obesity also plays a central role in the development of metabolic syndrome (MS) in children. Non-alcoholic fatty liver disease (NAFLD) is considered a manifestation of MS. Not only MS but also NAFLD seem to be inversely associated with serum bilirubin concentrations, an important endogenous tissue protector when only mild elevated. The aim of the study was to evaluate the association between serum bilirubin levels and the prevalence of MS and NAFLD in Italian obese children and adolescents. A retrospective cross-sectional study was performed in 1672 patients aged from 5 to 18 years. Clinical and laboratory parameters were assessed. NAFLD was measured by liver ultrasonography. The study was approved by the Ethical Committee of the Istituto Auxologico Italiano (research project code 1C021_2020, acronym BILOB). MS was present in 24% and fatty liver (FL) in 38% of this population. Bilirubin was not associated with FL and MS as a whole, but it was inversely associated only with selected components of MS, i.e., large WC, high blood pressure and high triglycerides. Our data suggest that bilirubin is not protective against MS and NAFLD in the presence of severe obesity.

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Relationship between Serum Indirect Bilirubin Level and Insulin Sensitivity: Results from Two Independent Cohorts of Obese Patients with Impaired Glucose Regulation and Type 2 Diabetes Mellitus in China

Cited by 17 publications

References 43 publications

Direct Bilirubin Levels Predict Long-Term Outcomes in Patients With Acute Coronary Syndrome Under Different Glucose Metabolism Status: A 6.5-Year Cohort Study of Three-Vessel Disease

Direct Bilirubin Levels Predict Long-Term Outcomes in Patients With Acute Coronary Syndrome Under Different Glucose Metabolism Status: A 6.5-Year Cohort Study of Three-Vessel Disease

Development and Validation of an Insulin Resistance Predicting Model Using a Machine-Learning Approach in a Population-Based Cohort in Korea

Association of Serum Bilirubin Level with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study of 1672 Obese Children

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