Association between serum bilirubin levels and progression of albuminuria in Taiwanese with type 2 diabetes mellitus

Abstract

Background To investigate the association between serum bilirubin (BIL) levels and the progression of albuminuria in type 2 diabetic Taiwanese. Methods Longitudinal data from January 2001 to June 2015 were retrospectively reviewed from Chang Gung Memorial Hospital in Taiwan. A total of 2877 type 2 diabetic patients with normal total BIL levels were divided into 4 groups according to BIL, with the highest BIL in the fourth group. The urinary albumin/creatinine ratio (UACR) trend and progression, as well as other laboratory measurements, were evaluated among the four groups. The cumulative incidence and Cox proportional hazard model analysis were performed to examine the relationship between BIL and the risk of albuminuria progression (AUPr). Results The mean duration of follow-up was 1.5 years (±1.37 years). The mean patient age, glycosylated hemoglobin level, and duration of diabetes were 62.52 years, 7.9%, and 3.94 years, respectively. A significant correlation was observed between BIL and both the UACR at baseline (P < 0.001) and the cumulative incidence of AUPr (log–rank test, P = 0.031). Hazard ratio (HR) analysis revealed that patients in the fourth BIL quartile had the lowest HR risk of AUPr among the four groups (adjusted HR = 0.70; 95% Confidence Interval = 0.56–0.89, P < 0.05). Conclusions Higher serum BIL levels are associated with a lower risk of AUPr in type 2 diabetes patients in Taiwan.

High‐normal unconjugated bilirubin is associated with decreased risk of chronic kidney disease in type 2 diabetes: A real‐world study

“…Interestingly, although some studies demonstrated a negative association between STB levels and the incidence and progression of CKD in T2DM subjects, 27,28,30 when distinguishing UCB from STB, the conclusion of the relationship between UCB and CKD was disputable in T2DM patients and the relevant studies were sparse. For example, a longitudinal observational study in T2DM subjects found that the subjects with the lowest STB levels (0.1–0.3 mg/dl) had the highest risk of developing CKD stage 3, and SB did not exceed 1.2 mg/dl in all subjects in this study 30 .…”

“…Interestingly, although some studies demonstrated a negative association between STB levels and the incidence and progression of CKD in T2DM subjects, 27,28,30 when distinguishing UCB from STB, the conclusion of the relationship between UCB and CKD was disputable in T2DM patients and the relevant studies were sparse.…”

“…59 Additionally, a retrospective study reported by Chan et al also displayed that the patients in the fourth STB quartile (1.0-1.3 mg/dl) had the lowest risk of albuminuria progression, suggesting that high-normal SB levels were also associated with the risk of CKD progression. 28 Consequently, it was reasonable to think that serum UCB not only could be used as a clinical indicator to assess the risk of CKD but also to evaluate the risk of CKD progression.…”

“…Interestingly, the study populations were mainly from Asia in the investigations on the association between SB and CKD in T2DM. 27,28,30,33,49,55,58 We hypothesised that since the incidence of neonatal unconjugated hyperbilirubinemia is significantly higher in Asian populations, 60 especially in East Asian populations, 61 which could be partly explained by either UGT1A1 polymorphism, 62 liver enzyme genes such as CYP2D6 polymorphism, 63 or an adaptive response to hepatitis virus infection. 64 Therefore, there may be higher baseline levels of UCB Asian populations compared with other populations, which indicates that the protective role of UCB in CKD is more obvious and detectable in the Asian population.…”

“…For example, a meta‐analysis consisting of 16 studies showed that elevated serum total bilirubin (STB) levels within a physiological range reduced the risk and mortality of CKD 26 . Similarly, several clinical studies in T2DM subjects also observed a reverse correlation between STB and CKD, 27–30 and follow‐up changes in STB were also found to be significantly associated with the progression of CKD in male patients with diabetes 29 . Although many studies investigated the association between serum bilirubin (SB) levels and CKD and the effect of bilirubin on CKD in general and diabetic populations, most discussions mainly focused on STB and did not distinguish conjugated bilirubin (CB) and unconjugated bilirubin (UCB) in their studies.…”