The role of neurohumoral factors in the persistence of aseptic bone inflammation in patients with diabetic neuroosteoarthropathy
Authors: Zaitseva E. L. , Kalandiya M. M. , Tokmakova A. Yu. , Malysheva N. M. , Nikankina L. V. , Galstyan G. R. 
Published: December 2022

BACKGROUND: Diabetic neuroosteoarthropathy (DNOAP, Charcot foot) is a relatively rare complication of diabetes mellitus (DM), which can lead not only to impaired support function of the lower limb in such patients, but also to high amputation. DNOAP is characterized by persistent aseptic inflammation of the bone structures of the foot, which creates significant ­difficulties in planning therapeutic measures. In the medical literature, there are data demonstrating the role of individual ­cytokines and neurohumoral factors in the prolongation of the inflammatory process in diabetes, however, there are currently very few studies that determine reliable markers of aseptic inflammation in DNOAP.

AIM: To study the effect of neurohumoral factors and advanced glycation end products on the activity of aseptic inflammation in the bone structures of the foot in patients with type 2 diabetes mellitus (DM2) and diabetic neuroosteoarthropathy.

MATERIALS AND METHODS. The study included 88 patients with type 2 diabetes (45 men, 43 women). Group 1 consisted of patients with DM2 and inactive DNOAP (n= 43), group 2 (n= 45) consisted of patients with DM2 and distal diabetic neuropathy without osteoarticular pathology. The diagnosis of diabetic neuropathy was based on the analysis of the clinical picture and indicators of peripheral sensitivity. Diagnosis of DNOAP and determination of its stage was based on clinical data, the results of infrared thermometry and radiology tests of the foot bones. General clinical assessment was used, radiology tests (X-ray, MRI), evaluation of CRP, calprotectin, copeptin, glutathione peroxidase 1 (GP1).

RESULTS. According to the results of examination and palpation of the feet, as well as the analysis of the temperature gradient of the skin of the affected and contralateral limb (infrared thermometry), DNOAP was detected and the stage of this complication was determined. The diagnosis of the chronic stage of DNOAP was confirmed by the results of MRI and the clinical picture (no difference in skin temperature on the symmetrical areas of the feet). According to the results of laboratory analysis, a statistically significant difference in copeptin values was revealed — in group 1 — 0.232 µg/ml [0.147; 0.342], in group 2 — 0.115 µg/ml [0.065; 0.203] (p>0.05) and CRP — in group 1 — 7.113 mg/l [2.453; 16.505], in group 2 — 2.187 mg/l [1.131; 5.567] (p>0.05), leukocyte levels in the groups did not differ significantly: group 1 — 7.86 [6.40; 9.00]*10^9, group 2 — 7.00 [6.00; 8.15] (p>0.05). There was a trend towards an increase in the level of calprotectin and glutathione peroxidase-1 in the DNOAP group, however, the differences were not significant. calprotectin — in group 1 — 1.948 [1.229; 2.969], in group 2 — 1.692 [1.16; 2.514] μg/ml and glutathione peroxidase-1 in group 1 — 24.72 [20.1; 31.82], in group 2 — 22.98 [18.94; 31.2] ng/ml.

CONCLUSION. In the study, statistically significant differences were obtained in the levels of copeptin and C-reactive protein: in patients with DNOAP, their values were significantly higher, which indicates the persistence of the aseptic inflammatory process in the bone tissue of patients even in the chronic stage of DNOAP. These data may help in deciding whether to use one or another method of unloading the affected joints, which will affect the clinical prognosis. The study of neurohumoral markers of arthropathy in the blood serum of patients with DM2 is carried out for the first time, and therefore it is difficult to compare with the results of other authors. It can be assumed that copeptin and CRP are significant markers of persistent inflammation of the osteoarticular structures of the foot in DNOAP.