Association Of Serum Bilirubin With Glucose, Lipid And Chronic Complications In Type 2 Diabetic Patients

Objective:To explore the association of serum bilirubin with glucose, lipid and chronic complications in type 2 diabetic patients, to compare the strength of correlation between total bilirubin, direct bilirubin and indirect bilirubin and diabetic complications, and to identify the antioxidant and anti-inflammatory effect of bilirubin.Methods:6640 subjects of type 2 diabetic patients admitted to the Department Of Endocrinology of Chinese PL A General Hospital from June 2007 to June 2013 were reviewed. We recorded and analyzed the baseline data, the complications of diabetes, history of drug use and laboratory test results. All the subjects were divided into four groups based on total bilirubin:Ql group(TBIL≤7.8μmol/L), Q2 group(7.8μmol/L<TBIL≤10.3μmol/L), Q3 group(10.3μmol/L<TBIL≤13.7μmol/L), Q4 group(TBIL>13.7μmol/L); direct bilirubin:Ql group(DBIL≤2.2μmol/L), Q2 group(2.2μmol/L<DBIL≤3.0μmol/L), Q3 group(3.0μmol/L<DBIL≤4.0μmol/L), Q4 group (DBIL>4.0μmol/L); indirect bilirubin:Ql group(IDBIL≤5.4μmol/L), Q2 group (5.4μmol/L<IDBIL≤7.3μmol/L), Q3 group (7.3μmol/L<IDBIL≤9.7μmol/L), Q4 group (IDBIL>9.7μmol/L).Results:1. HbAic and FPG showed a downward trend with the increase of total bilirubin levels, but the differenc was statistically significant only in men(HbA1c:8.6±2.2,8.6± 1.9,8.5±2.1,8.3±2.2,P<0.05;FPG:8.5±3.5,8.1±3.4,8.1±3.5,7.9±3.2, P<0.05).2hPG in all groups had no significant difference (P>0.05). Regardless of gender,LDL-C decreased significantly with the increase of bilirubin levels (P<0.01), while the HDL-C had significant difference between different levels of bilirubin only in the male patients. Moreover, TC in Q4 group was significantly lower than that of group Q1(in male:4.0±1.1 VS 5.0±1.4, P<0.01;in female:4.4±1.0 VS 5.3±1.3, P<0.01).TG had the similar trend.2. DBIL was significantly negatively correlated with HbA1c(r=-0.11 P=0.03) and FPG (r=-0.12, P<0.01) in male, however, TBIL and IDBIL had no correlation with HbA1c、FPG、2hPGRegardless of gender, DBIL was significantly negatively correlated with TC, TG, and LDL-C.3. In Logistic regression analyses showed that adjusted by age, gender, history of diabetes, BMI, smoking and other confounding factors and compared with Q1 group, the OR values for DR from TBIL Q2 group to Q4 group were 0.66,0.60,0.48, respectively (P<0.01). Meanwhile, that fromQ2 group to Q4 group of DBIL and IDBIL decreased significantly. The OR values of PDR had a similar trend with DR.4. The OR values for DN from TBIL Q2 group to Q4 group (0.51,0.37,0.48) were lower than that of Q1 group (P<0.01).The OR values(95%CI) for DN of DBIL Q4 group and IDBIL Q4 group were 0.40 (0.28-0.56) and 0.42 (0.30-0.59),which were lower than other three groups(P<0.01).After the adjustments of confounding factors, The OR values still had significant differences.5. Compared with Q1 group, the OR values for DPN of TBIL Q2-Q4 groups were 0.78,0.77,0.62(P=0.02).The OR values for DPN of DBIL Q2-Q4 groups declined 15%, 20% and 41%(P<0.01) and that of IDBILQ2-Q4 groups declined 20%,29% and 27% (P=0.02).ConclusionsLipid decreased gradually with elevated levels of serum bilirubin,and direct bilirubin were significantly negatively correlated with blood glucose in male patients. Bilirubin in three forms all had independent protective effects on diabetic retinopathy, nephropathy and neuropathy.