Effects Of Metformin On GDF15 And Body Fat Distribution In Prediabetic Patients: A Randomized Controlled Trial

Objective: To observe the changes of growth differentiation factor 15(GDF15)and body fat distribution in prediabetic patients after metformin application and to explore the possible mechanism.Methods:According to the inclusion criteria and exclusion criteria,selected 92 people with impaired glucose regulation(IGR)in Shijiazhuang from September 2018 to February 2019,they were randomly divided into experimental group(standard lifestyle intervention combined with metformin,46 people)and control group(standard lifestyle intervention,46 people).Body weight,body mass index(BMI),waist circumference(WC),body fat distribution,liver and kidney function,circulating levels of glucose,insulin,lipid,and GDF15 were measured in baseline and after one year.Compared the changes of above indexes in both groups before and after the intervention and explored the possible mechanism.Results:1.Comparison of baseline data between the two groups:There were no significant differences in cases,gender,age,family history of diabetes,past medical history,smoking history,drinking history,blood pressure,blood glucose,insulin levels,insulin resistance index(HOMA-IR),quantitative insulin sensitivity index(QUICKI),islet beta cell function index(HOMA-?),glycosylated hemoglobin(HBA1c),liver and kidney function,lipid,BMI,WC,body fat distribution,GDF15 between the two groups(P > 0.05).2.Spearman correlation analysis between GDF15 and other parameters of prediabetic patients in the two groups at baseline: GDF15 was positively correlated with age,WC and VAT(r=0.262,0.280,0.292,P < 0.05).3.Comparison of biochemical indicators between the two groups after one year:FBG,PBG,OGTT2 h insulin and HOMA-IR in the experimental group were lower than those in the control group,QUICKI and GDF15 were higher than those in the control group,with statistically significant differences(P<0.05).In the experimental group,after one year of intervention,total cholesterol(TC),fasting and OGTT2 h insulin,HOMA-IR,HOMA-?,HBA1 c,ALT and AST were lower than before,HDL,QUICKI and GDF15 were higher than before,and the difference was statistically significant(P<0.05).The incidence rate of type 2 diabetes was 21%.In the control group,compared with baseline,TC and HOMA-? were significantly decreased(P<0.05),fasting blood glucose(FBG)and GDF15 were significantly increased(P<0.05).The incidence rate of type 2 diabetes was 40%.4.Changes of body weight and body fat distribution in the two groups: After one year of intervention,there were statistically significant differences in changes of body weight,BMI,WC,area A fat mass and percentage between the two groups(P<0.05).In the experimental group,after one year of intervention,body weight,BMI,WC,upper limb fat mass,lower limb fat mass,total body fat mass,area A fat mass,visceral adipose tissue(VAT),and total lean tissue mass were lower than before,with statistically significant differences(P<0.05),especially area A fat mass and lower limb fat mass(P<0.05).In the control group,compared with baseline,the total lean tissue mass was significantly decreased(P<0.05),and the percentage of G area fat was significantly increased(P<0.05).5.Multiple linear regression analysis on the influencing factors of GDF15 in two groups after intervention:Metformin and age were the influencing factors of GDF15,and the correlation of Metformin was greater(?'=0.423,P<0.001;?'= 0.283,P = 0.018).6.Correlation analysis of the change GDF15 with changes of body weight,body fat distribution and blood glucose: The change in serum GDF15 from baseline in experimental group was significantly correlated(r=-0.344,P=0.032)with the decreasing of FBG.There was no association of FBG change with change in GDF15 in the control group(r=0.150,P=0.370).There was no correlation between the changes GDF15 and changes in body weight and body fat distribution in the two groups(P>0.05).Conclusions:1.Metformin treatment can reduce the rate of progression to type 2 diabetes in prediabetic patients.2.Metformin treatment can reduce blood glucose in prediabetic patients,which may be related to GDF15.3.Metformin treatment can reduce the body weight and abdominal fat mass,thus improving insulin sensitivity and reducing insulin resistance.4.In the prediabetic population,the increase of GDF15 is related to metformin.