Effects Of Sodium-glucose Co-transporter 2 Inhibitor On Insulin Sensitivity And Serum GPC-4 In Patients With Type 2 Diabetes Mellitus

Objective To investigate the effects of dapagliflozin on insulin sensitivity and serum glypican-4(GPC-4)levels in patients with type 2 diabetes mellitus(T2DM)according to observing the effect of dapagliflozin on T2 DM.Methods 80 patients with T2 DM were treated with dapagliflozin for 12 weeks.And observe the changes of blood glucose,blood lipid,insulin sensitivity and serum GPC-4..40 healthy subjects were taken as normal control(NGT).Taking the outpatients and inpatients of the Second Affiliated Hospital of Chongqing Medical University as the research objects.80 patients with T2 DM diagnosed for the first time without any hypoglycemic drugs or diet control were included.Observe the changes of blood glucose,blood lipid,insulin sensitivity and serum GPC-4 levels after 12 weeks of treatment with dapagliflozin.Forty age-matched healthy people recruited from routine physical examination were used as normal glucose control(NGT).Results The BMI,WHR,TG,LDL-C,FFA,FBG,2h PBG,Hb A1 c,FINS,PINS and HOMA-IR in T2 DM group were higher than those in NGT group(all P < 0.05),while the serum GPC-4 and HOMA-IS levels in T2 DM group were lower than those in NGT group.The level of total cholesterol in T2 DM group was lower than that in NGT group(P < 0.05),and the level of HDL-C in T2 DM group was higher than that in NGT group,but there was no significant difference(P > 0.05).After 12 weeks of treatment with dapagliflozin,the body weight,WHR,BMI,FFA,TG,TC,LDL-C,FBG,PBG,Hb A1 c and HOMA-IR of T2 DM group were significantly decreased(P < 0.05),HOMA-IS and serum GPC-4 levels were increased(P < 0.05),but there was no significant difference in HDL-C(P > 0.05).In order to explore the expression of serum GPC-4 in T2 DM patients with different BMI,HOMA-IR and blood glucose levels,we analyzed the subgroup of T2 DM patients,and found that the serum GPC-4 level in overweight and obese patients was higher than that in normal weight patients(P < 0.05),and the highest was in obese group.The serum GPC-4 level was lower in patients with poor blood glucose control(P < 0.05),especially in patients with Hb A1 c ≥ 9%.Serum GPC-4 levels in T2 DM patients with insulin resistance were higher than those without insulin resistance(P < 0.05).We analyzed the indexes of T2 DM group and NGT group,and found that serum GPC-4 level was positively correlated with body weight,WHR and BMI in NGT group(P < 0.05).In T2 DM group,serum GPC-4 level was positively correlated with body weight,BMI,FINS and HOMA-IR(P < 0.05).It was negatively correlated with Hb A1 c,FBG and PBG(P < 0.05).Hb A1 c,TG,TC,HDL,LDL,FFA,1 / HOMA-IR and HOMA-IS were used as independent variables,and GPC-4 was used as dependent variable for multiple regression analysis.The results showed that Hb A1c(β =-0.608,P = 0.000)and 1 / HOMA-IR(β =-2.566,P = 0.003)were independent influencing factors of serum GPC-4 level in patients with T2 DM.After treatment with dapagliflozin,the increase level of serum GPC-4 was positively correlated with the decrease level of Hb A1c(P < 0.05),but not with the change of HOMA-IR(P = 0.601).Conclusion Dapagliflozin can control the blood glucose,blood lipid and body weight of patients with type 2 diabetes mellitus,and improve the function of islet βcells.It can also increase the circulating GPC-4 level.However,its effect on serum GPC-4 may be related to the decrease of blood glucose,but not to the improvement of insulin sensitivity.