Decreased Physiological Serum Total Bile Acid Concentrations in Patients with Type 2 Diabetic Peripheral Neuropathy

Bile acids, amphipathic cholesterol metabolites, have been reported to have cytoprotective and neuroprotective effects in humans and animal models. The relationship of physiological serum total bile acid (TBA) levels with diabetic peripheral neuropathy (DPN), however, has not been determined. The purpose of this study was to investigate the relationship between physiological serum TBA and DPN.

In total, 856 patients with type 2 diabetes mellitus (T2DM) aged 20-89 years were enrolled in this cross-sectional study. Serum TBA was measured, and its relationship with DPN and other parameters was analyzed.

T2DM patients with DPN had significantly lower serum TBA compared with those without (P<0.01). Serum TBA was negatively associated with glycated hemoglobin A1C, plateletcrit, fibrinogen, urine albumin-to-creatinine ratio, vibration perception thresholds, and prevalence of DPN, peripheral arterial disease, and diabetic foot ulceration after adjustment for age, sex, and body mass index (P<0.01 or P<0.05). A graded association with prevalence of DPN and increase in serum TBA quartiles was observed (P for trend <0.01), and there was an 48.2% decreased risk of DPN in the highest quartile of serum TBA versus the lowest quartile (95% CI 0.299-0.617; P=0.000) after multivariate adjustment. Receiver-operating characteristic analysis revealed that the optimal cutoff point of serum TBA to indicate DPN was 2.85 μmol/L (sensitivity 77.6% and specificity 45.6%).

These findings suggest that lower physiological serum TBA level may be associated with the prevalence of DPN in T2DM patients and may be a potential biomarker for DPN.