Comparison of immunopathological mechanisms between obeseand non-obese type 2 diabetes mellitus patients

Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease with involvement of pro- and antiinflammatory cytokines and immune cells. In obesity, persistent low-grade inflammation is considered as a major contributor to the progression to type 2 diabetes mellitus. The aims of this thesis are (1) to investigate the association of immunopathological mechanisms with obesity in patients with T2DM, and (2) to obtain results that may help to provide more precise and personalized treatment modalities for T2DM because medicine is becoming more and more personalized day by day, and accordingly more precise treatment modalities are evolving. Therefore, this thesis study focused to obtain more personalized results by using ELISA and RT-PCRHRM while assessing cytokines and autoantibodies that might cause the disease. It is planned to identify the differences between the immunopathological mechanisms of obese and non-obese patients (also compared to healthy control group) since this interaction might provide new information about the prevention and treatment of T2DM. Twenty nine obese and 29 non-obese T2DM patients as well as 29 healthy volunteers who visited the endocrinology outpatient clinic of Al-Yermuk Educational Hospital and National Center for Diabetes Research and Treatment in Baghdad between 35-70 y.o. were involved in this study. Results: Serum levels of IL-34, IL37, GADA-65 IgM, TNF-α and Ghrelin were higher while serum levels of GADA-65 IgG and Adiponectin were lower in obese T2DM patients compared to non-obese T2DM patients. In addition, serum level of GADA-65 IgG was higher in non-obese T2DM patients compare to healthy controls. The genotype frequencies of IL-37 (IL-37 rs 3811047 SNP) and Ghrelin (GHRL rs 696217 SNP) gene polymorphisms were found to be higher in obese T2DM patients than in non-obese T2DM patients and healthy controls. However, the genotype frequencies of GADA-65/GAD-2 (GAD-2 rs 2236418 SNP) and Adiponectin (ADIPOQ rs 10937273 SNP) gene polymorphisms were found to be lower in obese T2DM patients than in non-obese T2DM patients and healthy control group. Statistically significant differences were detected among study groups for the immunological parameters examined in the study (p <0.0001). Conclusion: serum levels of immunological parameters (İL-34, İL-37, GADA-65 IgM, TNF-α, Ghrelin) and frequencies of gene polymorphisms of IL-37 and Ghrelin measured in the groups of this study were higher in obese T2DM patients compared to non-obese T2DM patients and healthy control group. Serum levels of GADA-65 IgG and Adiponectin as well as genotype frequencies of GAD65\GAD-2 and Adiponectin gene polymorphisms were found to be lower in obese T2DM patients than in nonobese T2DM patients and healthy control group. The findings show the increased levels of these immunological parameters in serum and of genotype frequencies of their gene polymorphisms show a possible relationship between T2DM and obesity. Keywords : Type 2 Diabetes Mellitus, obesity, cytokines, IL-34, IL-37, GADA-65 IgG\IgM, TNF- α, Adiponectin, Ghrelin, IL-37 rs381107, GAD-2 rs2236418, ADIPOQ rs 10937273, GHRL rs 696217, SNP