On the other hand, some authors highlighted the importance of pro-inflammatory cytokines in the pathogenesis of AD [22, 23]. disposal rate (eGDR) were calculated. Results The patients with AD had significantly higher IL-15, IL-6, and HOMAIR and lower eGDR than the controls ( 0.001, respectively) and first-degree relatives ( 0.001, respectively). Significantly higher IL-15 and IL-6 were FAE shown in the relatives with positive Ab as compared to the relatives without antibodies ( 0.001, respectively) and the controls ( 0.001, PF-562271 respectively). IL-15 negatively correlated with eGDR (= ?0.436, = 0.021) in LADA and positively with HOMAIR in LADA and T1D (= 0.507, 0.001; = 0.4209, 0.001). Conclusions Significantly higher IL-15 and IL-6 concentrations, HOMAIR, and markedly lower eGDR in newly diagnosed AD patients and first-degree relatives with positive anti-islet antibodies might suggest the role of these pro-inflammatory cytokines and insulin resistance in the pathogenesis of autoimmune diabetes. IL-15 and IL-6 might be used as biomarkers of the risk of autoimmune diabetes development, in particular IL-15 for LADA. Both methods of IR measurement appear equally useful for calculating insulin resistance in autoimmune diabetes. 1. Background The pathogenesis of autoimmune diabetes is usually complex and includes both genetic predisposition and environmental factors, such as viral infections, diet, and toxins . After an autoimmune attack by anti-islet antibodies, the pancreas is usually infiltrated by immune cells, PF-562271 such as CD4+ and CD8+ lymphocytes, as well as antigen-presenting cellsmacrophages, and dendritic cells [2, 3]. Elevated circulating levels of pro-inflammatory peptides produced by mononuclear cells, observed in patients with AD, strongly suggest a role of a disturbed balance between pro-inflammatory cytokines, such as interleukin-1 (IL-1), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-(IFN-(TGF-and TNF-by natural killer (NK) cells and increases immunoglobulin secretion [7C9]. Rothe et al. observed that in nonobese diabetic (NOD) mice, insulitis was associated with up-regulation of IL-15 gene expression . Increased concentration of IL-15 was also found in diabetic mice by Gupta et al. . Conversely, some studies have shown that IL-15 treatment reduces the development of diabetes in NOD mice, probably via a stimulatory effect of IL-15 on NK cells, suggesting a protective role for this cytokine in type 1 diabetes . IL-6 regulates glucose homeostasis by stimulating bowel L cells and pancreatic cells to produce and secrete glucagon-like peptide-1 (GLP-1), thereby improving insulin secretion [12, 13]. Some authors demonstrated an increased IL-6 concentration in T1D, while others found no differences in IL-6 concentrations between T1D patients and healthy controls, or even lower IL-6 concentration in T1D . In this light, the role of both cytokines in the pathogenesis of autoimmune diabetes seems still discursive. Insulin resistance is increasingly more often ascribed a role in the pathogenesis of autoimmune diabetes. The main mechanism proposed is the inhibition of insulin signaling, leading to increased inflammatory processes, amino acids, and free fatty acids concentrations. Latest decades yielded number of hypotheses about the interrelationship between insulin resistance and development of type 1 diabetes such as Fertile Field, accelerator, and double diabetes hypothesis. But until now, the precise role of IR in development and progression of type 1 diabetes has not been completely comprehended [15C17]. The euglycemic-hyperinsulinemic clamp as a reference method for measurement of insulin sensitivity is used, but because of invasive procedure is not in practical for use. The most frequently used formula is usually homeostatic model PF-562271 assessment-insulin resistance (HOMAIR). However, this index is not usually applicable in autoimmune diabetic patients because of their use of exogenous insulin. In 2000, Williams et al. described a method of measuring insulin resistance in T1D. On the basis of prior studies, they used some components, such as hypertension, waist-to-hip ratio (WHR), PF-562271 and glycated hemoglobin (HbA1c), to calculate a formula of estimated glucose disposal rate (eGDR). Further studies showed that eGDR results were comparable with results of euglycemic-hyperinsulinemic clamp . The aim of our study was to assay circulating IL-15 and IL-6 levels in patients with newly diagnosed AD, their first-degree relatives, and healthy controls in comparison with the presence of anti-islet antibodies and insulin resistance. All persons chosen for the study were patients with newly diagnosed autoimmune.
On the other hand, some authors highlighted the importance of pro-inflammatory cytokines in the pathogenesis of AD [22, 23]