How to cite this article: Nikiforov NG, Galstyan KO, Nedosugova LV, Elizova NV, Kolmychkova KI, Ivanova EA. Proinflammatory monocyte polarization in type 2 diabetes mellitus and coronary heart disease. Vessel Plus 2017;1:192-5.Aim: Type 2 diabetes mellitus (T2DM) is associated with rapid progression of atherosclerosis. There is no doubt that inflammation is involved in atherogenesis. Recent studies showed the relationship between the development of atherosclerotic plaque formation and the amount of pro-inflammatory (M1) activated macrophages in situ. Methods: The authors studied the ability of circulating monocytes isolated from patients with diabetes (n = 28), coronary heart disease (CHD) (n = 27) and healthy subjects (n = 50) to be activated into M1 phenotype in vitro. Results: Increased levels of basal and stimulated secretion of tumor necrosis factor alpha (TNF-α) was observed in diabetic patients compared with healthy subjects. On the contrary, in patients with CHD, decreased secretion of the pro-inflammatory cytokine, TNF-α, was found. A direct correlation between glycated hemoglobin (HbA1c) levels in T2DM patients and basal secretion of TNF-α from monocytes was observed. Conclusion: The authors found diametrically different responses of monocytes from T2DM and CHD under pro-inflammatory stimuli. Key words:Type 2 diabetes mellitus, coronary heart disease, M1/M2 monocyte polarization, oxidative stress, atherosclerosis, inflammatory ABSTRACTArticle history:

Актуальность. В начале 2000-х гг. в практике лечения сахарного диабета 2 типа (СД2) появилось принципиально новое на-правление -препараты инкретинового ряда. Применение ингибиторов фермента дипептидилпептидазы 4 типа (иДПП-4

Current treatment strategies for type 2 diabetes mellitus (T2DM) are based on using safe and effective hypoglycaemic agents for preventing diabetic vascular complications and reducing the risks associated with weight gain and hypoglycaemia. These goals may be achieved using new agents with a fundamentally new mechanism of action: inhibitors of dipeptidyl peptidase-4 (DPP-4i). However, the wide distribution of this enzyme in the body is associated with extraglycaemic DPP-4i effects, both positive and negative. Thus, it is important to develop and implement new DPP-4i agents for clinical practice. Aim. To investigate the efficacy and safety of a novel DPP-4i, gosogliptin, for use as monotherapy and in combination with metformin vs. vildagliptin as monotherapy and in combination with metformin for patients with drug-naive type 2 diabetes in a multicentre, open, randomized clinical trial. Materials and methods. We enrolled 299 drug-naive type 2 diabetes patients; 149 patients were randomized to receive gosogliptin and 150 patients received tovildagliptin. These groups had similar baseline characteristics. After randomization, 12 weeks of monotherapy was administered to both groups. Further, it was decided to continue the monotherapy or in combination with metformin, depending on each patient. The results after the first 12 weeks are presented in this paper. Results. After 12 weeks of monotherapy, HbA1c levels decreased significantly from 8.61% to 7.41% (p

AIMS:Investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor- (TNF-) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers and the effect of the course use of the combined metabolic drug Kokarnit as part of complex therapy on the dynamics of the severity of symptoms of DSPN and the cytokine phenotype in patients with long-term non-healing ulcers of the lower extremities MATERIALS AND METHODS:121 patients with T2DM, 79 without diabetic foot syndrome (DFS) and 42 patients with DFS were included. CD14+ monocytes were isolated from patients blood and stimulated by interferon- (IFN-) and interleukine-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF- and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation in all patients before taking the combined metabolic drug Kokarnit. Then they were randomly allocated either to the control group (57 people), to whom Kokarnit was added to standard treatment, or to the comparison group. After a 9-day course of application of Kokarnit, the dynamics of indicators was evaluated on a TSS scale. Assessment of cytokine status was carried out in 18 people with long-term non-healing ulcerative defects of the lower extremities, on the first and ninth day of treatment. RESULTS:A correlation was found between HbA1cand levels of stimulated secretion of TNF (r=0.726, p=0.027), CCL18 (r=-0.949, p=0.051) in patients with DSPN. In all patients with different duration of VDS, an increase in secretion of TNF- and CCL18 was observed (p0.05). However, stimulation of anti-inflammatory activation was not observed in patients with ulcerative defects lasting more than 6 months (p=0.033). The use of cocarnit in these patients had a decrease in stimulated secretion of TNF and an increase in CCL18. Throughout the entire observation period with the therapy, the score for the symptoms of polyneuropathy on the TSS scale in patients of the control group was statistically significantly higher. CONCLUSION:Against the background of therapy in patients of the main group, a statistically significant dynamics of indicators on the TSS scale was established. The cytokine modulating ability of Kokarnit to switch the cytokine status into the category of anti-inflammatory.