Abstract
To identify the factors associated with serum total bilirubin (STB) and determine whether STB is independently associated with diabetic retinopathy (DR) or diabetic kidney disease (DKD), 1,665 Chinese patients with type 2 diabetes (T2DM) (248 outpatients newly diagnosed with T2DM [NDM] and 1,417 inpatients previously diagnosed with T2DM [PDM]) were studied. Clinical and biochemical information was collected, and a single nucleotide polymorphism (rs6704078) of the UGT1A1 gene was genotyped in 1,059 individuals. Multiple linear regression showed that STB was associated with haemoglobin concentration, platelet count, and serum triglyceride concentration in NDM and PDM patients, and with serum albumin, duration of diabetes, and smoking in PDM patients. In patients with PDM, multiple logistic regression revealed that serum albumin was associated with DR (odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.87–0.96, p = 0.001) and DKD (OR = 0.93, 95% CI: 0.88–0.98, p = 0.005) after adjustment for STB, STB-related factors, and risk factors for DR and DKD. In addition, patients with the T allele of rs6704078 had higher STB (13.2 [10.4–17.9] μmol/L versus 11.8 (9.4–14.8) μmol/L; p < 0.001) and similar risks of DR or DKD to those without the T allele. Thus, serum albumin, but not STB, is associated with DR and DKD.
Highlights
Perhaps significantly, in addition to moderate hyperbilirubinemia, higher haemoglobin concentrations and low platelet counts characterize patients with Gilbert syndrome[15], and patients with this syndrome have been reported to have low risks of cardiovascular disease and diabetes[16]
In the participants with newly diagnosed T2DM (NDM), in whom there was no confounding by the use hypoglycaemic agents or the duration of diabetes, multiple linear regression analysis was conducted with ln-transformed serum total bilirubin (STB) as the dependent variable, and sex, age, body mass index (BMI), waist circumference, FPG, HbA1c, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum albumin, alanine transaminase, triglycerides, high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), creatinine, urinary albumin/creatinine ratio (UACR), high sensitivity C-reactive protein, white blood cell count, haemoglobin concentration, platelet count and smoking status as independent variables
In the patients with previously diagnosed T2DM (PDM), multiple linear regression analysis was conducted with ln-transformed STB as the dependent variable, and sex, age, BMI, waist circumference, FPG, HbA1c, SBP, DBP, serum albumin, alanine transaminase, triglycerides, HDL-c, LDL-c, creatinine, UACR, white blood cell count, haemoglobin concentration, platelet count and smoking status as independent variables
Summary
In addition to moderate hyperbilirubinemia, higher haemoglobin concentrations and low platelet counts characterize patients with Gilbert syndrome[15], and patients with this syndrome have been reported to have low risks of cardiovascular disease and diabetes[16]. It remains to be determined whether the relationship between STB and cardiovascular disease depends on haemoglobin concentration or platelet count in this syndrome. The significance of STB-related factors has not been established in patients with T2DM, and in all the previous studies of the relationship between STB and vascular diseases, a number of the potential confounders, such as haemoglobin concentration and platelet count, have not been adjusted for. We aimed to evaluate the relationships between STB and the prevalences of DR and DKD, while accounting for the effects of haemoglobin concentration, platelet count, and other blood parameters, in a Chinese population with T2DM
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