Effects Of Liraglutide On Serum FGF21 And PTP1B Levels In Obese Patients With Type 2 Diabetes Mellitus

Objective:Type 2 diabetes(T2DM)and obesity are increasingly prevalent worldwide.Previous study showed that obese patients with excessive fat accumulation suffered more risks of developing into T2 DM than those with normal body weight.Besides,most patients with T2 DM were often accompanied by other risk factors such as abnormal lipid metabolism and obesity,which could further accelerate the progression of T2 DM.Recent studies have found that human fibroblast growth factor 21(FGF21)and protein tyrosine phosphatase 1B(PTP1B)were to some extent involved in the development of chronic metabolic diseases such as T2 DM and obesity.Liraglutide is a representative drug of glucagon-like peptide-1(GLP-1)receptor agonist: it is a novel drug for the treatment of diabetes and obesity,and it has the effects on decreasing blood glucose levels,reducing body mass index(BMI),promoting the regeneration of islet beta cells,and improving insulin resistance(IR).Whether FGF21 and PTP1 B are involved in the process of reducing plasma glucose or body weight by liraglutide has not been reportde.This study is to explore the effects of liraglutide on serum FGF21 and PTP1 B levels in obese T2 DM patients.Methods:A total of 80 obese T2 DM inpatients in the Endocrinology Department of the Baoding First Central Hospital from March to December 2018 who received metformin or sulfonylurea treatment but had poor glycemic Ctrltrol were selected.40 cases were treated with liraglutide(LI group)on the basis of original oral hypoglycemic drugs,and the other 40 cases were treated with metformin and sulfonylurea(Ctrl group)for 16 weeks.In addition,40 healthy subjects in the Physical Examination Center of our hospital during the same period were collected as normal Control group(NC group).General information before and after treatment of LI and Ctrl groups as well as NC groups were recorded,such as body weight,waist circumference(WC),hip circumference(HC),metabolic indexes such as fasting plasma glucose(FPG),C-peptide,hemoglobin A1c(Hb A1c)and blood lipids were measured.Afterwards,body mass index(BMI),waist-hip ratio(WHR),homeostasis model assessment-insulin resistance(CP)(Homa-IR(CP)),homeostasis model assessment-islet(Homa-islet)were caculated.FGF21,PTP1 B levels were determined by enzyme-linked immunosorbent assay(ELISA)kits.The general data and metabolic indexes above were analyzed by statistical software,and the correlations between serum FGF21 and PTP1 B levels and relevant metabolic indexes were analyzed,respectively.P<0.05 was ctrlsidered statistically significant.Results:1.The body weight,BMI,WC,HC,WHR,HOMA-IR(CP)and the levels of FPG,Hb A1 c,TG,TC,LDL-C,FGF21,PTP1 B were higher in the LI group and Ctrl group than those in the NC group,(P <0.05),while the level of C-peptide,HDL-C and Homa-islet were lower than those in the NC group(P<0.05).2.After 16 weeks of treatment,the levels of Homa-islet,C-peptide and HDL-C in the Ctrl group and LI group were significantly increased,while body weight,BMI,WC,WHR,Homa-IR(CP)and the levels of FPG,Hb A1 c,TG,TC,LDL-C,FGF21 and PTP1 B were significantly decreased.Furthermore,all of the indexes above,except body weight,in the LI group were ameliorated more significantly when compared to those in the Ctrl group.3.Serum FGF21 level was positively correlated with body weight,BMI,WC,HC,WHR,FPG,C-peptide,Homa-IR(CP)and TG in obese T2 DM patients,respectively(r=0.663,0.229,0.457,0.377,0.276,0.347,0.246,0.391,0.499,respectively,P<0.05);Serum PTP1 B levels were positively correlated with body weight,BMI,WC,WHR,FPG,C-petide,Homa-IR(CP),respectively(r=0.310,0.328,0.279,0.355,0.300,0.228,0.337,respectively,P<0.05).Aftermultiple stepwise regression,it was demonstrated that body weight,Homa-IR(CP)and TG had a significant influence on the expression of serum FGF21 in obese T2 DM patients(P<0.05).Homa-IR(CP),WHR and BMI were the influencing factors of serum PTP1B(P <0.05).Conclusion:1.Serum FGF21 and PTP1 B were significantly higher in obese T2 DM patients and were associated with insulin resistance and lipid metabolism disorders.2.Liraglutide can reduce body weight,improve glycolipid metabolism disorders and insulin resistance.3.Treated by liraglutide,the biochemical and insulin functional indicators in obese T2 DM patients were improved,and the serum FGF21 level and PTP1 B level were decreased,suggesting that FGF21 and PTP1 B may play a role in the mechanisms.