Inverse Relationship Between Serum Bilirubin Levels and Diabetic Foot in Chinese Patients with Type 2 Diabetes Mellitus

BACKGROUND: Several studies demonstrated that bilirubin, a potent endogenous antioxidant, is a strong protective factor for many diabetic complications such as nephropathy, retinopathy, neuropathy, and vasculopathy. The purpose of this study was to assess the association between serum bilirubin levels and diabetic foot (DF) in Chinese patients with type 2 diabetes mellitus (T2DM).
MATERIAL AND METHODS: The present cross-sectional study of bilirubin levels in relation to DF was conducted in 1,269 T2DM patients with (n=578) and without (n=691) DF. Blood test results were obtained on hospital admission, including total bilirubin (T-BIL), direct bilirubin (D-BIL), and indirect bilirubin (I-BIL). Data on Wagner classification and amputation procedure in patients with DF were collected by reviewing electronic medical records. Univariate or multivariate analysis were performed to explore the association between bilirubin and DF.
RESULTS: Serum I-BIL levels were shown to play a protective role regarding the presence and severity of DF (OR=0.75, p=0.029 and OR=0.90, p=0.021, respectively). In addition, in a comparison of the lowest and highest tertiles of serum bilirubin concentration, the highest tertile of serum T-BIL (OR=0.51, p=0.011) and I-BIL (OR=0.28, p<0.001) was significantly related with a lower Wagner grade of DF. Patients with DF in the highest tertiles of T-BIL carried a significantly lower risk of amputation events than those in the lowest tertiles (OR=0.47, p=0.025).
CONCLUSIONS: The present study provided evidence that decreased serum bilirubin levels were independently associated with the presence and severity of DF and amputation events in patients with DF.

Keywords: Amputation, bilirubin, Diabetes Mellitus, Diabetic Foot, Diabetic Neuropathies, peripheral arterial disease