Effects Of Liraglutide On Serum LXA4 And Inflammatory Factor Levels In Obese Patients With Type 2 Diabetes Mellitus

Objective:As people’s dietary habits change and living standards continue to improve,the prevalence of type 2 diabetes mellitus(T2DM)and obesity has increased dramatically.The persistent chronic microinflammatory state and excessive fat accumulation in the body have become high risk factors for the development of T2 DM and promote the development of T2 DM and its complications.In recent years,studies have identified the involvement of lipoxin A4(LXA4)in the development of metabolic inflammatory syndrome(MIS)in T2 DM patients.Liraglutide is one of the representative glucagon-like peptide-1(GLP-1)receptor agonists,promotes inflammation regression while lowering body weight,lowering glucose,improving lipid disorders and improving insulin resistance.This study aims to investigate the effects of liraglutide on serum LXA4 and inflammatory factor levels in obese T2 DM patients,to provide new clinical evidence to support the application of liraglutide in type 2 diabetes and to promote its clinical promotion and use.Methods:84 obese T2 DM patients with substandard glycemic control were selected for the study.Patients were treated with metformin alone or metformin combined with glimepiride prior to enrolment and were randomly divided into two groups,Group OA: continued treatment with oral metformin or metformin combined with glimepiride,with dose adjustment according to blood glucose(if blood glucose was still substandard after the maximum amount of metformin alone,glimepiride could be combined as appropriate);Group LG: treatment with oral metformin or metformin combined with glimepiride;both were treated for 16 weeks.LG group: treatment with subcutaneous liraglutide in combination with the original hypoglycemic agent;all treated for 16 weeks.A further 40 healthy physical examination cases were collected as normal controls(NC group).Age,sex and duration of disease were recorded in NC,OA and LG groups;body mass indexes such as weight,height and waist circumference(WC)were recorded before and after treatment in NC,OA and LG groups;glucose metabolism indexes such as fasting venous blood glucose(FPG)and glycated hemoglobin(Hb A1c)were recorded;lipid indexes such as serum total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)were recorded.Body mass index(BMI)and insulin resistance index(HOMA-IR)were calculated;the concentrations of Lipoxin A4(LXA4),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were measured by Enzyme-linked immunosorbent assay(ELISA).The adverse reactions that occurred in the study subjects during the treatment period were recorded.SPSS 26.0 statistical software was applied to analyze and process the clinical indicators of all study subjects,analyze the correlation between serum LXA4 levels and the above indicators,and explore the independent influencing factors of serum LXA4 levels.If P<0.05,the difference can be considered statistically significant.Results:1.Compared with the NC group,weight、HC、WC、WHR、BMI、FPG、FINS、HOMA-IR、Hb A1c、TC、TG and LDL-C levels were increased in the OA and LG groups before treatment(P<0.05).2.After 16 weeks of treatment in the OA and LG groups,HDL-C levels increased and Body weight、HC、WC、WHR、BMI、FPG、FINS、HOMA-IR、Hb A1c、TC、TG and LDL-C levels decreased compared with those before treatment(P<0.05);after 16 weeks of treatment,HDL-C levels in the LG group were higher than those in the OA group(P<0.05).Body weight、HC、WC、WHR、BMI、FPG、FINS、HOMA-IR、Hb A1c、TC、TG and LDL-C levels were lower in the LG group than in the OA group after 16 weeks of treatment(P<0.05).3.compared with the NC group,serum LXA4 levels were lower(P<0.05)and TNF-α and IL-6 levels were higher(P<0.05)in the OA and LG groups before treatment.after 16 weeks of treatment in the OA and LG groups,serum LXA4 levels were higher(P<0.05)and TNF-α and IL-6 levels were lower(P<0.05)compared with those before treatment;after 16 After 16 weeks of treatment,the serum LXA4 level in the LG group was higher than that in the OA group(P<0.05),and the TNF-α and IL-6 levels were lower than that in the OA group(P<0.05).4.Serum LXA4 levels in the OA and LG groups were negatively correlated with body weight、HC、FPG、FINS、HOMA-IR、TC、TG、IL-6、and TNF-α(r:-0.229,-0.253,-0.267,-0.245,-0.231,-0.359,-0.221,-0.285,-0.291,respectively,P<0.05).Multiple linear regression analysis showed that HOMA-IR and body weight were influential factors for serum LXA4(P <0.05).Conclusions:1.Liraglutide is effective in reducing body weight,lowering blood glucose,improving dyslipidemia and insulin resistance in obese T2 DM patients.2.Serum LXA4 levels are reduced and IL-6 and TNF-α levels are increased in obese T2 DM patients,suggesting a microinflammatory state in T2 DM patients.3.After liraglutide treatment,serum LXA4 levels increased and IL-6and TNF-α levels decreased in obese T2 DM patients,suggesting that LXA4 may be involved in the process of liraglutide promoting the regression of the inflammatory response.