Abstract
Type 2 diabetes mellitus (DM2) is strongly associated with other comorbidities such as obesity, atherosclerosis, and hypertension. Obesity is associated with sustained low-grade inflammatory response due to the production of proinflammatory cytokines. This inflammatory process promotes the differentiation of some myeloid cells, including myeloid-derived suppressor cells (MDSCs). In this study, two groups of individuals were included: DM2 patients and non-DM2 individuals with similar characteristics. Immunolabeling of CD15+ CD14- and CD33+ HLA-DR-/low was performed from whole peripheral blood, and samples were analyzed by flow cytometry, and frequencies of MDSCs and the relationship of these with clinical variables, cytokine profile (measured by cytometric bead array), and anthropometric variables were analyzed. The frequency of CD33+ HLA-DR-/low MDSCs (that produce IL-10 and TGF-β, according to an intracellular detection) is higher in patients with DM2 (P < 0.05), and there is a positive correlation between the frequency of CD15+ CD14- and CD33+ HLA-DR-/low MDSC phenotypes. DM2 patients have an increased concentration of serum IL-5 (P < 0.05). Also, a negative correlation between the frequency of CD15+ CD14- MDSCs and LDL cholesterol was found. Our group of DM2 patients have an increased frequency of mononuclear MDSC CD33+ HLA-DR-/low that produce TGF-β and IL-10. These cytokines have been associated with immune modulation and reduced T cell responses. DM2 and non-DM2 subjects show a similar cytokine profile, but the DM2 patients have an increased concentration of IL-5.
Highlights
According to the American Diabetes Association (ADA), diabetes mellitus is a metabolic disease characterized by severe hyperglycemia due to defects in insulin secretion or the lack of proper action of this hormone in the target tissues
Laboratory data, and anthropometric data were analyzed in order to determine whether differences were present due to heterogeneity of the population or whether differences in myeloid-derived suppressor cells (MDSCs) cells were associated with other parameters such as metabolic markers of disease or cardiovascular risk factors
To demonstrate that the CD33+ HLA-DR-/low MDSCs are an immunoregulatory subset of cells, we did an intracellular staining of IL-10 and TGF-β and we found that this subpopulation produces these cytokines (Figure 2), suggesting that the immunosuppressive function of the MDSCs is increased in the DM2 patients
Summary
According to the American Diabetes Association (ADA), diabetes mellitus is a metabolic disease characterized by severe hyperglycemia due to defects in insulin secretion or the lack of proper action of this hormone in the target tissues. Obesity has been associated with low-grade chronic inflammatory processes, and several cytokines such as tumor necrosis factor alpha (TNF-α) have been shown to be elevated in obese individuals due to an increased activity of adipose tissue-derived cytokine production and insulin resistance [11, 12]. Other bioactive molecules such as leptin, IL- (interleukin-) 6, resistin, and monocyte chemoattractant protein 1 (MCP-1) have been associated with insulin resistance [13,14,15,16,17]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call