Effect Of Liraglutide On Serum ANGPTL8 Level In Obese Patients With Type 2 Diabetes Mellitus

Objective:Type 2 diabetes mellitus(T2DM)is a considerable health issue that exists widely in the world.It is distinguishing feature is hyperinsulinemia,hyperglycemia,dyslipidemia and obesity.Liraglutide is a agent of the glucagon-like peptide-1(GLP-1)receptor agonist,which regulate obesity status,reduce body weight,stimulate pancreaticβcell regeneration,promote insulin secretion and improve insulin resistance(IR).It has been reported that human angiopoietin like protein 8(ANGPTL8)is involved in the occurrence and development of T2DM,dyslipidemia and obesity.However,there have been no relevant reports on whether liraglutide can improve glucose and lipid metabolism and IR by regulating ANGPTL8 level.The aim of this study was to investigate the changes of serum ANGPTL8 levels in obese T2DM patients before and after liraglutide intervention,so as to provide a new target for the prevention and treatment of T2DM.Methods:Sixty cases of obese T2DM patients in Baoding first central hospital were selected as the research objects.They were treated with lifestyle intervention combined with metformin,but their glucose status was not maintained well.On the basis of the original oral drug treatment,liraglutide treatment was started as liraglutide treatment group(T2DM).At the same time,80 healthy subjects in the physical examination department were selected as the control group.body mass index(BMI)<28 kg/m~2was divided into normal glucose tolerance normal weight group(NGT-NB group),a total of 40 cases;BMI≥28 kg/m~2was divided into normal glucose tolerance obesity group(NGT-OB group),a total of 40 cases.OGTT was performed in all subjects to determine the glucose metabolism.Body weight,height,waist circumference(WC),hip circumference(HC),fasting plasma glucose(FPG),glycohemoglobin A1c(Hb A1c),fasting serum insulin(FINS),total cholesterol(TC),triglyceride(TG),low-density lipoprotein-cholesterol(LDL-C),and high-density lipoprotein-cholesterol(HDL-C)were measured.Serum ANGPTL8 levels were determined by enzyme-linked immunosorbent assay(ELISA).Waist hip ratio(WHR),body mass index(BMI),homeostasis model assessment forβ-cell function(HOMA-β)and homeostasis model assessment for insulin resistance(HOMA-IR)were calculated.T2DM group received liraglutide intervention for 16 weeks and then re-measured the above indexes.SPSS software was used to analyze the general data and metabolic indexes of the three groups,and the correlation between serum ANGPTL8 level and each index was analyzed.To investigate the influencing factors of serum ANGPTL8 level.P<0.05 was considered statistically significant.Results:1.Research CompletionIn the T2DM group,60 obese T2DM patients were included,and five of them withdrew from the study due to diarrhea,nausea and other gastrointestinal adverse reactions.The symptoms were relieved after the drug withdrawal.All the others took medicine according to the doctor’s advice,and no hypoglycemia occurred.2.Comparison of general clinical data and biochemical indexesCompared with NGT-NB group,the levels of body weight,BMI,WC,HC,WHR,FPG,FINS,Hb A1C,HOMA-IR,TG,TC and LDL-C in NGT-OB group and T2DM group were increased(P<0.05),and the levels of HOMA-βand HDL-C were decreased(P<0.05).Compared with NGT-OB group,the levels of BMI,HC,FPG,FINS,Hb A1c,HOMA-IR and TC in T2DM group were increased(P<0.05),while the levels of HOMA-βand HDL-C were decreased(P<0.05).After 16 weeks of treatment,the levels of HDL-C and HOMA-βin T2DM group were increased,and the levels of body weight,BMI,WC,HC,WHR,FPG,FINS,Hb A1C,HOMA-IR,TG,TC and LDL-C were decreased compared with before treatment(P<0.05).3.Comparison of serum ANGPTL8 levels in each groupThe level of serum ANGPTL8 in NGT-NB group,NGT-OB group and T2DM group(267.4±80.1pg/m L、421.3±71.7pg/m L、654.0±228.1pg/m L)was gradually increased,with statistical significance(P<0.05).After 16weeks of treatment(433.3±143.5pg/m L),serum ANGPTL8 level in T2DM group decreased compared with before treatment(654.0±228.1pg/m L)(P<0.05).4.Correlation between serum ANGPTL8 and various indexesSerum ANGPTL8 level was positively correlated with BMI,WC,WHR,FPG,HOMA-IR,FINS,Hb A1c,and TG levels in obese T2DM patients(r=0.612,0.386,0.477,0.526,0.957,0.520,0.499,0.639,P<0.05).5.Multiple stepwise regression analysis for influencing factors of serum ANGPTL8 levelMultiple stepwise regression analysis was made with serum ANGPTL8as the dependent variable,and BMI,WC,WHR,FPG,HOMA-IR,FINS,Hb A1c,TG as independent variables.Results showed that BMI,HOMA-IR and TG were the influencing factors of serum ANGPTL8 level.Conclusion:1.Serum ANGPTL8 levels were increased in obese people with normal glucose tolerance and obese T2DM patients,but the increase was more significant in obese T2DM patients.BMI,HOMA-IR and TG were the influencing factors for the level of ANGPTL8.2.Liraglutide can reduce body weight,improve glucose and lipid metabolism disorders and insulin resistance in obese T2DM patients.3.After treatment with liraglutide,serum ANGPTL8 level decreased,insulin resistance and glucose and lipid metabolism indexes improved in obese T2DM patients,suggesting that liraglutide may play the above role by regulating ANGPTL8 expression.