Leukocyte Composition and Immunophenotype of the Blood Lymphocytes in Women with Type 2 Diabetes Mellitus and Obesity
Background. There is an opinion that changes in some indicators of natural and adaptive immunity in patients with type 2 diabetes mellitus (DM) and overweight are caused by concomitant obesity, as the adipose tissue is the potent secretory organ that produces many cytokines, particularly adipokines playing a key role in various immune responses. It is known that the level of the main adipokines, which regulate the adipose tissue, in the human peripheral blood (PB) is determined on the basis of human sexual dimorphism. Purpose of the study — to elucidate the question of the extent, to which the observed changes in the leukocyte composition and lymphocyte immunophenotype in type 2 DM in women are determined by obesity, due to the significant sex differences in the secretion of some adipokines involved in controlling the function of the immune system. Materials and methods. The study included 24 women aged 40 to 65 years with newly diagnosed type 2 DM, who were divided into 2 subgroups: the first one — with a body mass index (BMI) < 25 kg/m2 and the second one — with BMI ≥ 30 kg/m2. The total number of leukocytes in the PB was counted using hematology analyzer. Leucocyte vomposition was determined in smears of the PB per 200 cells stained by Pappenheim. Surface antigens of lymphocytes against membrane antigens: CD3, CD4, CD8, CD20 and CD56 — were labelled by monoclonal antibodies marked with fluorescein isothiocyanate or phycoerythrin. Results. The increase in the total number of leukocytes in the PB of obese patients was more significant than in patients with a normal BMI, i.e. 23.1 versus 14.5 % (p < 0.05). The highest leukocytosis was observed in patients with DM type 2 and obesity, reached 7.61 × 109/L on the average. In the subgroup of healthy women and female patients with normal body mass, the absolute number of segmented neutrophils in the PB of patients with DM type 2 in relation to that of normoglycemic women had increased on average by 20.3 %, while in obese women this ratio was 29.1 % (p < 0.05). The absolute number of monocytes in the PB in these subgroups was increased by an average of 59.2 % in lean (p < 0.05) and 64 % in obese (p < 0.05). The majority of women with newly diagnosed DM type 2 and normal values of body weight have only a slight and statistically non-significant increase in the absolute number of CD4+T- and CD8+T-cells. The majority of patients with type 2 DM and obesity showed a statistically significant increase in the absolute number of natural killer cells (CD56+-cells) in the PB. Conclusions. In female patients with DM type 2 and obesity, there is a more significant change in the composition of leukocytes (increased number of neutrophils and monocytes) and immunophenotype of blood lymphocytes (increasing the number of CD4+Т- and CD56+-cells) than in women with DM 2 type and a normal BMI, which indicates a more significant low-grade chronic inflammation in them and explains the cause of a more severe course of DM type 2 in obesity. The findings are consistent with the recent data where efficiency of some oral hypoglycemic drugs, such as metformin, is largely due to their anti-inflammatory action.
Full Text:PDF (Русский)
Afanasieva VV, Zak KP, Kondratska IM, Siemionova TA. Content, ultrastructure and function of blood monocytes in patients with type 2 diabetes and metabolic syndrome. Endokrynolohiia. 2009; 14(2):201-8. Ukrainian.
Zak KP, Popova VV. Immune intervention therapy in type 1 diabetes (analytical review). Diabet. Ozhirenie. Metabolicheskiy sindrom. 2015; 6(IV):31-44. Ukrainian.
Zak KP. The role of neutrophils in the pathogenesis of type 1 diabetes in humans (analytical review with the inclusion of own data). Mizhnarodnyi endokrynolohichnyi zhurnal. 2016; 2(74):130-9. Ukrainian.
Zak KP, Man'kovs'kij BN, Kondrackaja IN, Popova VV, Saenko JA, Lipskaja OE, Semionova TA, Afanas'eva VV. Immunity in patients with 2 types diabetes mellitus with concomitant metabolic syndrome/ obesity. Report 1. Endokrynolohiia. 2013; 18(1): 27-36. Ukrainian.
Zak KP, Man'kovskij BN, Kondrackaja IN, Popova VV, Saenko JA, Semionova TA, Korpacheva-Zinich OV, Tron'ko EN, Ivanchenko OV. Immunity in patients with 2 types diabetes mellitus with concomitant metabolic syndrome. Report 2. Role of adiponectines (interleukin-6, tumor necrosis factor alpha, leptin and adiponectin). Report 2. Endokrynolohiia. 2013; 18(2): 26-32. Ukrainian.
Zak KP, Tron'ko MD, Popova VV, Butenko AK. Diabetes. Immunity. Cytokines. K.: Kniga-pljus, 2015; 488 p. Russian.
Kondrackaja IN, Zak KP, Man'kovskij BN, Melnichenko SV, Korpacheva-Zinich LV, Korol VD. The level of circulating leptin in the blood of patients with metabolic syndrome and type 2 diabetes // Ukrainskyi kardiolohichnyi zhurnal. 2009; 2:30-33. Ukrainian.
Lichiardopol R, Popescu LD, Ionescu I. et al. Abdominal obesity in type 1 and type 2 diabetes patients. Diabetologia. 2008; 51(1):335.
Wannamethee SG, Lowe GDO, Rumbley A, Cherry L, Whincup PH, Sattar N. Adipokines and risk of type 2 diabetes in older men. Diabetes Care. 2007; 30(5):1200-05. DOI: 10.2337/dc06-2416.
O’Rourke RW, Kay T, Lyle EA, Traxler SA, Deveney CW, Jobe BA, Roberts CT Jr, Marks D, Rosenbaum JT. Alterations in peripheral blood lymphocyte cytokine expression in obesity. Clin Exp Immunol. 2006; 146(1):39-46. DOI: 10.1111/j.1365-2249.2006.03186.x
Åkesson C, Uvebrant K, Oderup C, Lynch K, Harris RA, Lernmark Å, Agardh C-D, Cilio C M. Altered natural killer (NK) cell frequency and phenotype in Latent Autoimmune Diabetes in Adults (LADA) prior to insulin deficiency. Clin Experim Immunol. 2010; 161(1):48-56. DOI: 10.1111/j.1365-2249.2010.04114.x.
Chang FY, Shaio MF. Decreased cell-mediated immunity in patients with non-insulin-dependent diabetes mellitus.Diabetes Res Clin Pract. 1995; 28(2):137-46.
Dinarello CA, Donath MY, Mandrup-Poulsen T. Role of IL-1beta in type 2 diabetes. Curr Opin Endocrinol Diabetes Obes. 2010; 17(4):314-21. DOI: 10.1097/MED.0b013e32833bf6dc.
Wannamethee SG, Papacosta O, Lawlor DA, Whincup PH, Lowe GD, Ebrahim S, Sattar N. Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women’s Heart Health Study. Diabetologia. 2012; 55(1):80-7. DOI: 10.1007/s00125-011-2284-4.
Donath MY. Multiple benefits of targeting inflammation in the treatment of type 2 diabetes. Diabetologia. 2016; 59(4):679-82. DOI: 10.1007/s00125-016-3873-z.
Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov. 2014; 13(6):465-76. DOI: 10.1111/dom.12172.
Fernández-Real JM, Pickup JC. Innate immunity, insulin resistance and type 2 diabetes. Diabetologia. 2012; 55(2):273-8. DOI: 10.1007/s00125-011-2387-y.
Ford ES. Leukocyte count, erythrocyte sedimentation rate, and diabetes incidence in a national samples of US adults. Am J Epidemiol. 2002; 155(1): 57-64. DOI: 10.1093/aje/155.1.57.
Harwood HJ. The adipocyte as an endocrine organ in the regulation of metabolic homeostasis. Neuropharmacology. 2012; 63(1):57-75. DOI: 10.1016/j.neuropharm.2011.12.010.
Donath MY, Dalmas É., Sauter NS., Böni-Schnetzler M. Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity. Cell Metab. 2013; 17(6):860-72. DOI: 10.1016/j.cmet.2013.05.001.
Kolb H, Mandrup-Poulsen T. An immune origin of type 2 diabetes? Diabetologia. 2005; 48(6):1038-50. DOI: 10.1007/s00125-005-1764-9.
Kondratska I, Zak K, Man’kovsky B. Plasma levels of leptin and adiponectin in patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MS). J. Diabetes. 2009; 1(1):A-172.
Lilja M, Rolandsson O, Norberg Ml. Leptin independently predicts diabetes in Swedish men. Diabetologia. 2010; 53(1):394.
Marchetti P. Islet inflammation in type 2 diabetes. Diabetologia. 2016; 59(4):668-72. DOI: 10.1007/s00125-016-3875-x.
van der Weerd K, Dik WA, Schrijver B, Schweitzer DH, Langerak AW, Drexhage HA, Kiewiet RM, van Aken MO, van Huisstede A, van Dongen JJ, van der Lelij AJ, Staal FJ, van Hagen PM. Morbidly obese human subjects have increased peripheral blood CD4+ T cells with skewing toward a Treg- and Th2-dominated phenotype. Diabetes. 2012; 61(2):401-8. DOI: 10.2337/db11-1065.
Qin H, Lee I-F, Panagiotopoulos C, Wang X, Chu AD, Utz PJ, Priatel JJ, Tan R. Natural killer cells from children with type 1 diabetes have defects in NKG2D-dependent function and signaling. Diabetes. 2011; 60(3):857-66. DOI: 10.2337/db09-1706.
Womack J, Tien PC, Feldman J, Shin JH, Fennie K, Anastos K, Cohen MH, Bacon MC, Minkoff H. Obesity and immune cell counts in women. Metabolism. 2007; 56(7):998-1004. DOI: 10.1016/j.metabol.2007.03.008.
Kumar S, Wilson B, Watson L, Alsop J. Obesity is associated with poorer clinical outcomes following insulin initiation for patients with type 2 diabetes. Diabetologia. 2009; 52(1).
Dworacka M, Winiarska H, Borowska M, Abramczyk M, Bobkiewicz-Kozlowska T, Dworacki G. Pro-atherogenic alterations in T-lymphocyte subpopulations related to acute hyperglycaemia in type 2 diabetic patients. Circ J. 2007; 71(6): 962-7.
Rodríguez A, Gómez-Ambrosi J, Catalán V, Rotellar F, Valentí V, Silva C, Mugueta C, Pulido MR, Vázquez R, Salvador J, Malagón MM, Colina I, Frühbeck G. The ghrelin O-acyltransferase-ghrelin system reduces TNF-α-induced apoptosis and autophagy in human viaceral adipocytes. Diabetologia. 2012; 55(11):3038-50. DOI: 10.1007/s00125-012-2671-5.
Panagiotakos DB, Pitsavos C, Yannakoulia M, Chrysohoou C, Stefanadis C. The implication of obesity and central fat on markers of chronic inflammation: The ATTICA. Atherosclerosis. 2005; 183(2): 308-15. DOI:10.1016/j.atherosclerosis.2005.03.010.
Turer AT, Scherer PE. Adiponectin: mechanistic insights and clinical implications. Diabetologia. 2012; 55(9):2319-26. DOI: 10.1007/s00125-012-2598-x.
This work is licensed under a Creative Commons Attribution 4.0 International License.
© "Publishing House "Zaslavsky", 1997-2018