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.

Fan Zhang,Yingyun Gong,Hongwen Zhou,Yizhe Ma,Li Zhou,Zhenzhen Fu,Wei Guan,Wen Guo,Wanzi Jiang,Hui Liang

doi:10.1155/2020/5681296

Abstract

Background Serum bilirubin is an endogenous antioxidant that has protective effects against obesity-related metabolic diseases. Objectives This study aimed to evaluate the characteristics of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) and their relationships with insulin sensitivity in obese patients with impaired glucose regulation and type 2 diabetes mellitus (IGR/T2DM) in China. Patients and Methods. Cohort 1 comprised obese patients (n = 71) was divided into the IGR/T2DM group (n = 38, obesity with IGR/T2DM) and control group (n = 33, obesity without IGR/T2DM). Insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique (HEC) with glucose disposal rate (GDR, M value). Cohort 2 comprised obese patients with IGR/T2DM who underwent metabolic surgery (n = 109) as complementary to cohort 1. Insulin sensitivity was evaluated with the Matsuda Index and homeostatic model assessment of insulin sensitivity (HOMA-IS). Results In cohort 1, TBIL, DBIL, and IBIL were higher within the physiological range in the IGR/T2DM group compared with the control group; IBIL was positively correlated with M value (r = 0.342, p=0.044) in the IGR/T2DM group, and multivariate logistic regression showed that IBIL might be independent protective factors against insulin resistance (odds ratio (OR) = 0.602; 95% confidence interval (CI): 0.413–0.878; p=0.008). In cohort 2, at 1 month after metabolic surgery, serum bilirubin levels (TBIL, DBIL, and IBIL) increased, and the percentage change in IBIL was positively correlated with the change of the Matsuda Index (r = 0.195, p=0.045). Conclusions The relationships between different types of bilirubin and insulin sensitivity varied. Serum indirect bilirubin might be a protective factor that enhances insulin sensitivity.

Highlights

Obesity remains one of the most prominent risk factors for disease widely prevalent across the world
No postoperative complications or deaths occurred after surgery. ere were significant decreases in body weight (BW) and body mass index (BMI) at 1 month after surgery compared with baseline. e Matsuda Index and homeostatic model assessment of insulin sensitivity (HOMA-IS) increased significantly; fasting plasma glucose (FPG), fasting insulin (FINS), and fasting C-peptide (FC-p) decreased significantly at 1 month after surgery compared with baseline, indicating an enhancement in insulin sensitivity. e serum bilirubin levels (TBIL, direct bilirubin (DBIL), and indirect bilirubin (IBIL)) increased within the physiological range at 1 month after surgery compared with baseline
The characteristics of various types of serum bilirubin levels and their relationships with insulin sensitivity were analyzed in obese patients with or without impaired glucose regulation (IGR)/ type 2 diabetes mellitus (T2DM). e cohort 1 data indicated that compared to the simple obese patients, serum bilirubin levels were higher within the physiological range, and IBIL was positively correlated with insulin sensitivity in obese patients with IGR/T2DM

Summary

Introduction

Obesity remains one of the most prominent risk factors for disease widely prevalent across the world. Insulin resistance is strongly associated with obesity-related impaired glucose regulation (IGR) and T2DM, and oxidative stress and inflammation are potential etiological factors. Recent studies have shown that a mild increase in the bilirubin level within the physiological range has a International Journal of Endocrinology protective effect against obesity-related metabolic diseases [3,4,5]. Erefore, a clearer appreciation of associations between different types of bilirubin (TBIL, DBIL, and IBIL) and insulin sensitivity will help us to understand the role of bilirubin in obese patients with IGR/T2DM. E increase in serum bilirubin levels showed the same trend as the enhancement in insulin sensitivity after metabolic surgery. Is study aimed to use two cohorts to evaluate the characteristics of various types of bilirubin and their relationships with insulin sensitivity in obese patients with IGR/ T2DM in China. It is hoped that our clinical study provides valuable evidence for subsequent more in-depth basic research on the improvement of obesity-related impaired glucose metabolism

Materials and Methods

Discussion

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Conclusions