The role of the immune system in mechanism of metformin therapeutic effect in patients with type 2 diabetes

• Main Authors: K.P. Zak, V.L. Orlenko, V.V. Popova, S.V. Melnichenko, Ya.A. Saenko, К.M. Tronko, A.V. Kulikovskaya, К.Yu. Ivaskiva
• Format: Article
• Language: English
• Published: Publishing House Zaslavsky 2017-08-01
• Series: Mìžnarodnij Endokrinologìčnij Žurnal
• Subjects: immunity; type 2 diabetes; treatment with metformin
• Online Access: http://iej.zaslavsky.com.ua/article/view/110024
• ISSN: 2224-0721; 2307-1427

Background. Metformin is one of the most prescribed hypoglycemic drugs of the first line of treatment for patients with type 2 diabetes (T2D). However, the mechanism of its therapeutic effect has not been sufficiently studied. At the same time, T2D is considered a disease of an inflammatory nature, wherein different immune responses are disturbed. However, only single articles are devoted to the role of the immune system in the mechanism of the therapeutic action of metformin. Purpose of the study. Elucidation of the question to what extent different types of leukocytes, immunophenotype of lymphocytes and some cytokines are involved in the mechanism of the therapeutic action of metformin. Materials and methods. A group of patients of both sexes with a newly diagnosed T2D with BMI of 33.1 ± 1.3 kg/m2 who had not yet taken hypoglycemic agents and a group of normoglycemic healthy individuals of the same age and sex were examined. The number of leukocytes in blood was determined using the hematological analyzers, and the leukocyte composition — in Pappenheim stained smears. Immunophenotype of lymphocytes (CD3+ T, CD4+ T, CD8+ T, CD56+) — by flow cytometry using the FACStar plus cytofluorimeter. The content of different cytokines (I-1b, TNF-a and IL-10) — with immunosorbent ELISA assay. Results. The metformin therapy of newly diagnosed T2D patients with obesity leads to normalization of the increased number of leukocytes, neutrophils and monocytes, as well as a decrease in CD4+ T cells in the blood, especially in patients with high BMI. A characteristic feature of the therapy is a sharp decrease in anti-inflammatory cytokines (IL-1b and TNF-a) that were elevated before treatment. The obtained data indicate significant disorders of natural and adaptive immunity in T2D and confirm the hypothesis about the inflammatory nature of this disease. Conclusions. The favorable therapeutic effect of metformin in T2D, especially complicated by obesity, is largely due to the normalization of inflammation and immunity indices.