Abstract
BACKGROUND: Although bilirubin has been generally regarded as a waste with potential neurotoxicity at high levels, a few clinical studies suggest a potential protective role of physiological serum total bilirubin (TBIL) concentrations in diabetic peripheral neuropathy (DPN). However, the pathological mechanisms underlying the relationship remain poorly understood. The objective of this study was to explore the relationship between serum TBIL and DPN, and clinical and laboratory parameters. METHODS: Serum TBIL was measured in 1342 patients with type 2 diabetes mellitus (T2DM). The relationship between TBIL and DPN and other parameters was analyzed. RESULTS: Serum TBIL levels were significantly lower in T2DM patients with DPN, and were independently and negatively associated with vibration perception thresholds (VPT) (P < 0.01 or P < 0.05). Moreover, serum TBIL was negatively associated with neutrophil and white blood cell counts, fibrinogen, and the prevalence of hypertension, diabetic foot ulceration, peripheral arterial disease, diabetic nephropathy and diabetic retinopathy (P < 0.01 or P < 0.05). Additionally, serum TBIL was an independent decisive factor for the presence of DPN after multivariate adjustment. Compared to the highest quartile of TBIL, the lower quartiles were associated with a significantly increased risk of DPN (P < 0.01). Last but most importantly, the analysis of receiver operating characteristic curves revealed that the best cutoff value for serum TBIL to predict DPN was 10.75 μmol/L (sensitivity 54.6% and specificity 62.9%). CONCLUSIONS: These findings suggest that lower physiological serum TBIL may be associated with the presence of DPN due to its decreased anti-inflammatory and vascular protective effects.