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The Metabolic Profile Of Overweight/obese Type 2 Diabetic Patients And The Effect Of Glucagon-like Peptide-1 Receptor Agonist On Patients' Metabolic Indicators

Posted on:2020-10-09Degree:MasterType:Thesis
Country:ChinaCandidate:X L LiFull Text:PDF
GTID:2434330578483530Subject:Internal Medicine
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Objective:To analyze the difference of metabolic profiles among overweight/obese diabetic patients with or without coronary heart disease and subjects of normal glucose tolerance(NGT),in order to explore the mechanism of diabetes and related cardiovascular diseases.Methods:From January 2018 to January 2019,140 subjects were included in this study.There were 74 overweight/obese diabetic patients,among which 40 patients were complicated with coronary heart disease,34 diabetic patients of normal weight and 32 NGT subjects.Metabolites were detected with LC-MS and OPLS-DA.The metabolic profiles were compared among different groups.Results:1.Clinical indicators showed that diabetic patients had severer metabolic disorders and more cardiovascular risk factors than NGT subjects.2.Compared with NGT subjects,the metabolic profile of diabetic patients is significantly different.In addition,compared with those with normal weight,the metabolic profile of overweight/obese diabetic patients is different.3.The metabolic profiles of diabetic patients with and without coronary heart disease were significantly different.Conclusion:Compared with those of normal glucose tolerance,the metabolic profiles of diabetic patients were significantly changed.Further analysis suggested that the metabolic profiles of overweight/obese and normal weight diabetic patients were significantly different,as well as those with and without coronary heart disease.Objective:To study the effect of short-term GLP-1RA on metabolism of overweight/obese patients with type 2 diabetes mellitus.Methods:From Jaunary 2018 to January 2019,90 overweight/obese type 2 diabetes patients(body mass index(BMI≥25kg/m2)admitted to the endocrinology department of fuwai hospital were selected as research objects,including 30 cases in the routine treatment group and 60 cases in the GLP-1RA group.All patients in the routine treatment group received oral hypoglycemic drugs or combined basic insulin therapy.In the GLP-1RA group,0.6mg-1.2mg liraglutide was injected subcutaneously on the basis of conventional treatment,once a day for 3 months.1.BMI,Wc,body fat content,MBP,HbA1c,TG,TC and ldl-c were compared between the two groups before and after treatment.2.The effect of different treatment methods on insulin resistance index(HOMA-IR)and islet function(HOMA-β)of patients was also evaluated.3.Leptin,adiponectin and fibroblast growth factor-21(FGF21)levels and their changes before and after treatment were compared between the GLP-1RA group and the routine treatment group,and relevant factors were analyzed.4 Framingham score was used to evaluate the changes of cardiovascular risk before and after treatment in the two groups.Results:1.Changes in clinical metabolic characters were compared between two groups:weight,BMI,Wc,body fat,visceral fat content and MBP decreased significantly greater in GLP-1RA group(changes in weight:-5.9±3.7 vs-0.9±1.8 kg;changes in BMI:-1.9±1.0 vs-0.2±0.9 kg/m2;changes in Wc:-6.9 ±4.8 vs 0.0±1.7 cm;changes in body fat:-3.0±2.4 vs 0.6 ±0.8%;changes in visceral fat content:-2.6 ±2.5 vs 0.6±0.8%;changes in MBP:-11.0±9.5 vs-4.9±9.6 mmHg,P values all<0.01).HbAlc decreased significantly in both groups after treatment,but the decrease was not significantly different(changes in HbAlc:-2.3±1.7 vs-1.7±1.2%,P=0.14).2.Change in insulin sensitivity were compared between two groups:after treatment,HOMA-IR decreased significantly in GLP-1RA group(5.32±4.46 vs 4.80±3.02 mmol/L*uU/ml,P<0.05),while it showed no significant change in the routine treatment group(4.26±3.39 vs5.75±4.72 mmol/L*uU/ml,P>0.05).HOMA-β did not change after treatment in two groups(P>0.05),while under curve area of C peptide increased significantly in patients of diabetes duration within 10 years after GLP-IRA treatment(8.45±3.85 vs9.05±3.51ng/ml,P<0.05).3.Changes in cytokines were compared between two groups:after treatment,leptin and FGF21 in the GLP-1RA group were significantly decreased,and adiponectin was significantly increased(P values all<0.05),while there was no significant change in cytokine levels before and after treatment in the routine treatment group(P values all>0.05).Multiple linear regression analysis(stepwise model)was used to analyze the related factors of changes in cytokines.Change in adiponectin was correlated with baseline total cholesterol,baseline BMI,BMI change and GLP-1RA treatment(P=0.05,0.01,0.04 and 0.03,respectively).Change in leptin was correlated with baseline leptin,baseline BMI,body fat change and GLP-1RA treatment(P=0.0008,0.0056,0.0019 and 0.0033,respectively).Change in FGF21 was correlated with baseline FGF21,baseline fasting C-peptide and GLP-1RA treatment(P=0.0001,0.1184 and 0.0025,respectively).4.Changes in cardiovascular risk were compared between two groups:after treatment,both male and female experienced significant reductions in FRS and risk of primary cardiovascular events in GLP-1RA group(P values all<0.05),while there was no significant change in cardiovascular risk in the routine treatment group after treatment(P>0.05).Conclusion:1.GLP-1RA could significantly improve the metabolism of overweight/obese diabetic patients,including weight and body fat content reduction,blood glucse and blood pressure decrease and insulin sensitivity improvement.2.GLP-1RA could improve the lipid metabolism disorder of patients by improving their adipokines:reducing leptin,increasing adiponectin,and lowering the level of fibroblast growth factor 21.3.GLP-IRA could reduce the risk of cardiovascular disease in overweight/obese patients with type 2 diabetes by improving cardiovascular related metabolic indicators...
Keywords/Search Tags:Overweight/Obesity, Type 2 diabetes mellitis, Coronary heart disease, Metabolomics, Glucogan like peptide-1 receptor agonist(GLP-1RA), Type 2 diabetes melliturs, Cardiovascular risk
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