Romanian Society of Pharmaceutical Sciences

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CHANGES IN THE SERUM PROINFLAMMATORY CYTOKINES IN PATIENTS WITH ELEVATED HOMA-IR AND TYPE 2 DIABETES MELLITUS

DANIELA LIXANDRU1,2, ELENA VIOLETA BĂCANU3*, BOGDANA VÎRGOLICI1, HORIA VÎRGOLICI1, ALEXANDRU PETRUŢA2, MARIUS EMIL BĂCANU4, PAUL GAGNIUC3, CONSTANTIN IONESCU-TÎRGOVIŞTE3, CRISTIAN SERAFINCEANU1,3

1.University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
2.Institute of Biochemistry of the Romanian Academy, Bucharest, Romania
3.”N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Disease, Bucharest, Romania
4.National Institute of Expert Medical and Recovery of Working Capacity, Bucharest, Romania

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The first aim of this study was to find associations of two inflammatory markers (TNF-α and IL-6) with different metabolic variables in type 2 diabetic patients. The second aim in studying the proinflammatory cytokines was to perform a comparative study in diabetic patients divided according to the severity of insulin resistance. In this study, 138 type 2 diabetic patients, aged between 40 and 80, were enrolled. According to the HOMA-IR (the homeostatic model assessment estimated insulin resistance) values, the diabetic patients were divided in three groups: group 1 with HOMA-IR ≤ 3 (arbitrary units), group 2 with HOMA-IR between 3 and 5 (arbitrary units) and group 3 with HOMA-IR ≥ 5 (arbitrary units). The plasma values for proinflammatory markers (TNF-α, IL-6 and leptin), for surrogate markers of insulin resistance (insulin, C peptide and proinsulin) were determined by ELISA methods. Respiratory burst (RB) of isolated peripheral blood mononuclear cells (PBMC) was measured by chemiluminescence. In group 2 versus 1, RB (p<0.05), TNF-α (p<0.03) and uric acid (p<0.02) were higher and in group 3 versus 1, RB (p<0.05), TNF-α (p<0.05), IL-6 (p<0.02), leptin (p<0.05), proinsulin (p<0.01), C peptide (p<0.001) were higher. In diabetic patients, TNF-α was correlated with proinsulin (r=0.65, p<0.05), RB (r=0.73, p<0.05), IL-6 (r=0.30, p<0.05) and with the duration of diabetes (r=0.77, p<0.05), while IL-6 was correlated with RB (r=0.28, p<0.05) and with the duration of diabetes (r=0.26, p<0.05). In conclusion, in type 2 diabetic patients, serum TNF-α was strongly correlated with proinsulin and with monocyte respiratory burst. Patients with HOMA-IR higher than 3 (arbitrary units) had increased levels of proinflammatory cytokines, severe dyslipidemia and raised monocyte respiratory burst.