Human leukocyte antigen (HLA)-G is a nonclassical MHC class I molecule with modulatory effects on NK and T cells. Unlike classical HLA class I molecules, HLA-G has seven isoforms, three of which are soluble. Soluble HLA-G molecules are reportedly able to transduce negative signals to immune cells after interacting with their corresponding receptors. The expression of these molecules plays significant roles in maternal tolerance against semi-allogenic fetuses. Overexpression of HLA-G in tumors and increased serum levels of soluble HLA-G have been reported in different malignancies, and these changes may be involved in tumoral immune evasion and cancer progression. To improve immune responses against tumor cells, the downmodulation of HLA-G by siRNA or blocking monoclonal antibodies can be helpful in cancer immunotherapy. Additionally, HLA-G can be considered a potential biomarker for the diagnosis and/or prognosis of certain cancers. Although polymorphism of the HLA-G gene-coding region is more limited than in classical HLA class I, some genetic variations in regulatory regions of the gene control the expression level of this molecule. Furthermore, epigenetic factors such as infections may affect the expression of HLA-G in infection-related cancers.
Aim: Although, the effectiveness of metformin in diabetes treatment is well established, its preventive effect in the development of diabetes is still unclear in real world. We aimed to determine the effectiveness of metformin therapy as a single preventive agent in patients with prediabetes in a cohort study (IDPS). Study Design: In this prospective observational study. Place and Duration of Study: Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Methodology: We included 410 patients with prediabetes (168 metformin user, 242 non-users), who participated in IDPS. To determine the association between metformin use and incidence of type 2 diabetes, Cox proportional hazard method, Kaplan-Meier and log Rank test were used. Results: In fully adjusted model for all confounders, significant hazard ratio (HR) for staying prediabetes rather than returning to normal was detected in male group of metformin non-user (HR: 2·41 [95% CI 1.01-5.79]; P<0·05) and those metformin non-user who had both Impaired Fasting Glucose and Impaired Glucose Tolerance (IFG & IGT) (HR: 2.13 [95% CI 1.05-4.34]; P=0·04). There was no significant difference in terms of developing diabetes risk between metformin users and non-users. Conclusion: This study evidenced that males and patients with IFG & IGT who had not used metformin are at higher risk to staying prediabetes than returning to normal.
Background We aimed to develop a risk model, monitoring the FDRs of patients with type 2 diabetes, who have normal glucose tolerance, to predict the onset of developing diabetes and prediabetes. In this study, 1765 FDRs of patients with type 2 diabetes mellitus, who had normal glucose tolerance, were subjected to statistical analysis. Diabetes risk factors including anthropometric indices, physical activity, fast plasma glucose, plasma glucose concentrations two-hour after oral glucose administration, glycosylated hemoglobin, blood pressure, and lipid profile at the baseline were considered as independent variables. Kaplan-Meier, log Rank test, univariate, and multivariable proportional hazard Cox regression were conducted. The optimal cut point for risk score was created according to receiver operating characteristic curve (ROC) analysis. Results The best diabetes predictability was achieved by a model in which waist to hip ratio (WHR), HbA1c, OGTT and the lipid profile were included. The best prediabetes risk model included HbA1c, systolic blood pressure, the lipid profile, and the oral glucose tolerance test (OGTT). These multivariable risk models were compared with FPG, HbA1c, and OGTT. The predictive efficiencies of models were higher than FPG and HbA1c; however the best predictive model of the current study showed comparable predictive efficiency to OGTT-AUC. Additionally, both diabetes models showed better performance than FINDRISC. Conclusion We recommend regular tests for FDRs of patients with type 2 diabetes to predict the risk of diabetes and prediabetes by using the OGTT-AUC. As a health check assessment tool, our diabetes models showed a more precise predictor compared to FINDRISC in our population.
Introduction: The prevalence of diabetes in Iranian adults is 9.5% with high morbidity and mortality. Here, we aimed to develop a risk model, monitoring the FDRs of patients with type 2 diabetes, who have normal glucose tolerance, to predict the onset of developing diabetes and prediabetes. Methods: A total of n = 1765 FDRs of patients with type 2 diabetes mellitus, who had normal glucose tolerance, were subjected to statistical analysis. Diabetes risk factors including anthropometric indices, physical activity, fast plasma glucose, plasma glucose concentrations two-hour after oral glucose administration, glycosylated hemoglobin, blood pressure, and lipid profile at the baseline were considered as independent variables. Kaplan-Meier, log Rank test, univariate, and multivariable proportional hazard Cox regression were conducted. The optimal cut point for risk score was created according to receiver operating characteristic curve (ROC) analysis. Results: The best diabetes predictability was achieved by a model in which waist to hip ratio, HbA1c, area under oral glucose tolerance curve (OGTT-AUC) and the lipid profile were included. The best prediabetes risk model included HbA1c, OGTT-AUC, systolic blood pressure, and the lipid profile. The predictive efficiencies of models were higher than FPG and HbA1c; however, the predictive efficiency of multivariable models were comparable to OGTT-AUC alone. Additionally, diabetes models and OGTT-AUC showed better performance than FINDRISC.Discussion: We recommend regular tests for FDRs of patients with type 2 diabetes to predict the risk of diabetes and prediabetes by using the OGTT-AUC. As a health check assessment tool, our diabetes models showed a more precise predictor compared to FINDRISC in our population.
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