Association between Serum Cystatin C and Diabetic Foot Ulceration in Patients with Type 2 Diabetes: A Cross-Sectional Study

Abstract

Serum cystatin C (CysC) has been identified as a possible potential biomarker in a variety of diabetic complications, including diabetic peripheral neuropathy and peripheral artery disease. We aimed to examine the association between CysC and diabetic foot ulceration (DFU) in patients with type 2 diabetes (T2D). 411 patients with T2D were enrolled in this cross-sectional study at a university hospital. Clinical manifestations and biochemical parameters were compared between DFU group and non-DFU group. The association between serum CysC and DFU was explored by binary logistic regression analysis. The cut point of CysC for DFU was also evaluated by receiver operating characteristic (ROC) curve. The prevalence of coronary artery disease, diabetic nephropathy (DN), and DFU dramatically increased with CysC (P < 0.01) in CysC quartiles. Multivariate logistic regression analysis indicated that the significant risk factors for DFU were serum CysC, coronary artery disease, hypertension, insulin use, the differences between supine and sitting TcPO₂, and hypertension. ROC curve analysis revealed that the cut point of CysC for DFU was 0.735 mg/L. Serum CysC levels correlated with DFU and severity of tissue loss. Our study results indicated that serum CysC was associated with a high prevalence of DFU in Chinese T2D subjects.

Figure 1

Prevalence of diabetic foot, coronary artery disease, and diabetic nephropathy by CysC quartiles. Quartile 1, CysC: ≤0.58 mg/L; Quartile 2, CysC: 0.58–0.7 mg/L; Quartile 3, CysC: 0.7–0.87 mg/L; Quartile 4, CysC: ≥0.87 mg/L. ^∗ P < 0.001, compared with the first quartile; ^# P < 0.001, compared with the second quartile; ^& P < 0.001, compared with the third quartile. DFU, diabetic foot; CAD, coronary artery disease; DN, diabetic nephropathy.

Figure 2

ROC analysis of CysC and creatinine to indicate diabetic foot for all diabetes participants. For CysC, AUC = 0.740, 95% confidence interval, 0.683–0.798; identified cut-off value = 0.735 mg/L; Youden index = 0.360; sensitivity: 73.9%; specificity: 62.1%.

Figure 3

ROC analysis of CysC and creatinine to indicate DPN for nonclinical renal dysfunction patients. For CysC, AUC = 0.715; 95% confidence interval, 0.649–0.781; identified cut-off value = 0.735 mg/L; Youden index = 0.332; sensitivity, 66.2%; specificity, 67.0%.