Urinary Neopterin in Patients with Diabetes Mellitus and Foot Ulcers

Abstract

Increased urinary or serum concentrations of neopterin have been reported in disorders associated with systemic immune activation, e.g. viral infections, cancer, or autoimmune diseases, but the data on neopterin concentrations in patients with diabetes mellitus are limited. The aim of the present study was to investigate urinary neopterin concentrations in patients with diabetes mellitus and with or without diabetic foot. Urinary neopterin was determined by high-performance liquid chromatography in 51 patients with diabetes mellitus, including 19 patients with diabetic foot, and 18 healthy controls. Neopterin concentrations were significantly increased in patients with diabetes mellitus compared to controls (mean ± standard deviation; 221 ± 149 vs. 139 ± 66 μmol/mol creatinine; Mann-Whitney U test, p = 0.003). Urinary neopterin concentrations in patients with or without diabetic foot were identical (224 ± 113 vs. 219 ± 169 μmol/mol creatinine). No significant difference was also observed between patients with type 1 and type 2 diabetes mellitus, between patients treated with insulin compared to patients not treated with insulin, patients with or without diabetic retinopathy, with or without diabetic neuropathy, with or without diabetic nephropathy, with or without ischemic heart disease, with or without ischemic disease of lower extremities, and with or without ischemic cerebrovascular disease. Atrend of higher neopterin concentrations was observed in patients with any complication of diabetes compared to no complications (234 ± 164 vs. 176 ± 73 μmol/mol creatinine), and compared to controls, urinary neopterin was significantly increased only in patients with complications. No significant correlation was observed between urinary neopterin and glycosylated hemoglobin (rs = - 0.14, p = 0.39) or the duration of diabetes (rs = 0.25, p = 0.09). In conclusion, present results demonstrate that urinary neopterin is increased in patients with diabetes mellitus. No differences were observed in urinary neopterin concentrations based on type of diabetes, therapy or presence of diabetic foot, and urinary neopterin did not correlate with the glycosylated hemoglobin levels or duration of diabetes. Increased urinary neopterin concentrations in patients with diabetes mellitus is associated with the presence of complications and may reflect systemic immune activation associated with atherosclerosis.

Effect of comorbidity on urinary neopterin in patients with breast carcinoma

“…The presence and number of comorbid conditions, most of which are disorders related to atherosclerosis, also determine the prognosis in patients with breast carcinoma (Satariano & Ragland 1994). Neopterin concentrations were found to be increased in patients with atherosclerosis (Tatzber et al 1991;Weiss et al 1994) or diabetes mellitus (Melicharova et al 2007). We therefore originally hypothesized that urinary neopterin will be increased in breast carcinoma patients in the presence of comorbid conditions compared with patients without any comorbidity.…”

“…Both malignant neoplasms and atherosclerosis-related disorders are associated with systemic immune and inflammatory activation (Wachter et al 1989;Tatzber et al 1991;Weiss et al 1994;Melicharova et al 2007). The presence of systemic inflammatory or immune response may be assessed by measuring serum or plasma cytokine concentrations.…”

Intestinal permeability, vitamin A absorption, alpha-tocopherol, and neopterin in patients with rectal carcinoma treated with chemoradiation

“…Increased urinary and serum neopterin concentrations have been reported in patients with different primary tumors, including metastatic colorectal carcinoma, and high neopterin concentrations are indicative of poor prognosis in this tumor [12,35]. Increased neopterin concentrations were also described in patients with atherosclerosis [36][37][38]. An increase in urinary neopterin was observed in cancer patients treated with chemotherapy [39] or radiation [40].…”