Cathepsin-D, Adiponectin, TNF-α, IL-6 and hsCRP plasma levels in subjects with diabetic foot and possible correlation with clinical variables: A multicentric study

Diabetic foot, characterized by a pronounced inflammatory reaction, decreased collagen content and biosynthesis and accelerated degradation are crucial in wound healing. Cathepsin D, an aspartic endopeptidases implicated in cell growth, apoptosis, and its inhibitor has been reported to reverse the inhibition of collagen biosynthesis in wounded rat skin with diabetes. To date, the increased proteolytic activity of Cathepsin D in diabetic foot has not been evaluated and the pathogenic significance of the inflammation has received little attention. Of the patients [with ulcer (n = 211) and without ulcer (n = 208)], 89.73% had type 2 diabetes. Subjects with diabetic foot ulcer showed higher median plasma level of Cathepsin D [556.3 (312.6–587.3) RFC/ml vs 306.3 (92.6–337.3) RFC/ml], TNF-α [96.6 (79.9–121.5) ng/ml vs 8.4 (7.1–9.20) ng/ml], IL-6 [32.2 (8.52–48.4) ng/ml vs 4.9 (4.5–5.6) ng/ml], hsCRP [12.6 (11.2–14.1) mg/ml vs 3.90 (3.50–4.60) mg/ml] and lower median plasma levels of adiponectin [8.50 (7.10–9.5) ng/ml vs 13.3 (12.1–14.2) ng/ml]. A positive correlation was found between grades of ulcer, BMI, A1c and retinopathy for Cathepsin D, for adiponectin, between grades of ulcer, BMI, retinopathy, nephropathy & smoking, for IL-6, between grades of ulcer, BMI, nephropathy, CAD & smoking, for hsCRP, grades of ulcer, BMI, LDL-C, nephropathy & smoking, while total cholesterol, nephropathy, PAD, smoking and neuropathy for TNF-α.