| ObjectiveTo observe the effects of exenatide and insulin on body weight,blood pressure,blood glucose,blood lipid metabolism,liver and kidney function,inflammatory factors and intima-media thickness of carotid artery(cIMT)in patients with type 2 diabetes mellitus(T2DM).to explore whether exenatide has the effect of improving atherosclerosis and its possible mechanism.MethodsEighty patients with type 2 diabetes who were treated in the endocrinology clinic of Beijing Hospital from March 2015 to June 2017 were selected.A total of 66 patients with type 2 diabetes who met the criteria were randomly divided into two groups.59 subjects were included in the analysis for a total of 52 weeks.The metabolic indexes such as body weight,HbAlc,fasting blood glucose(FPG),blood lipid,uric acid,hsCRP,fibrinogen(FIB)and carotid intima-media thickness were compared between the two groups.According to the baseline carotid intima thickness,the exenatide group was divided into atherosclerotic group and non-atherosclerotic group,and the differences of carotid intima-media thickness and other metabolic indexes were compared between the two groups.Results1.By the end of the study,there were 1 case in insulin group and 6 cases in exenatide group,and 32 cases in insulin group and 27 cases in exenatide group.Except for gender and diastolic blood pressure(male/female 19/8 vs 14/18,80.18 ±9.65 vs 75.15±9.11 mmHg),the baseline characteristics of patients in the premixed insulin group and the exenatide group reached a good balance.The average age of the subjects in the two groups was 58.85±12.54 vs ± 13.32 years,the course of diabetes was 6.59 ±5.32vs 7.81 ±6.02,fasting blood glucose was 10.38±2.95 vs 10.81±2.52 mmol,HbA1c 8.67±1.03 vs 8.32±0.96%the rate of carotid atherosclerosis in type 2 diabetic patients with type 2 diabetes was64.41%(38/59),and 71.87%(23/32)vs 55.6%(15/27)respectively.2.From 4 weeks of enrollment to the end of 52 weeks of follow-up,there were significant differences in body weight and BMI between the two groups.The body weight in the insulin group increased gradually compared with the baseline,and the maximum weight gain was 1.86 ±2.88kg in the insulin group,and decreased gradually compared with the baseline in the exenatide group.The maximum weight loss was-3.38 ±3.45kg.By the end of 52 weeks of treatment,the body weight of insulin treatment group and exenazeptide treatment group was 1.57 ±2.96 vs-2.21 ±3.43 kg respectively compared with the baseline.After treatment with isenazeptide,compared with the baseline BMI normal group,the weight loss in the overweight and obese group was more obvious,the lowest at 40 and 32 weeks respectively,and then slightly increased,but there was no significant difference in the baseline weight between the overweight and obese group and the overweight and obese group at 52 weeks(-0.33±1.93 vs-1.00 ± 1.05 kg/m2,p=0.32,respectively).After 52 weeks of treatment,BMI increased 0.13 12.15kg/m2 in atherosclerosis progression group(n=10)and decreased-0.99kg/m2 in atherosclerosis improvement group(n=17),but there was no significant difference between the two groups(paired 0.15).After 52 weeks of treatment,fasting blood glucose(-1.05±3.24mmol/L,-2.39±3.40mmol/L)and glycosylated hemoglobin(HbAlc)(-1.32±1.53%,-1.09± 1.42%)decreased compared with the baseline in the exenatide group and the insulin group,but there was no significant difference between the two groups.There was no significant difference in the number of HbA1c reaching the standard and the rate of reaching the standard between the two groups(62.96%and 71.87%respectively).3.Both exenatide treatment group and insulin treatment group can achieve good blood glucose control After 52 weeks of treatment,compared with the baseline,fasting blood glucose decreased in both exenatide group and insulin group(-1.05±3.24mmol/L vs-2.39±3.40mmol/L),but there was no significant difference.Glycosylated hemoglobin HbAlc decreased(-1.32±1.53%vs-1.09±1.42%),but there was no significant difference.There was no significant difference between the two groups in the number of cases of glycosylated hemoglobin reaching the standard(23 cases of vs,17 cases)and the rate of reaching the standard(62.96%vs 71.87%).At 52 weeks of treatment,fasting blood glucose in the exenazeptide group decreased significantly compared with the baseline(-1.51 ±3.60 mmol/L)in the weight loss group,and gradually increased in the weight gain group(1.16 ±2.28mmol/L),but there was no statistical difference(p=0.066).Compared with the baseline,HbAlc decreased significantly in the weight loss group(-1.71±1.39 mmol/L)and slightly decreased in the weight gain group(-0.39±1.07mmol/L)(p=0.024).4.The levels of total cholesterol and low density lipoprotein cholesterol in the exenatide group were lower than those in the insulin group,and there was significant difference in total cholesterol between the two groups at 16 weeks and 40 weeks after drug intervention(-0.52±0.98mmol/L vs 0.07±0.95 mmol/Lat 16 weeks and-0.50 ± 1.14 vs 0.23±1.03 mmol/L at 40 weeks.5.At the end of 52 weeks of treatment,the 8-OHdG of exenatide group and insulin group was-2.45±0.74vs-2.00 ±0.75 compared with the baseline data,and there was significant difference between the two groups(p<0.058),but there was no significant difference between the two groups(p<0.058).The NT-proBNP of the two groups was-103.55±39.47 vs-84.11±27.95,which was significantly different from the basepline(p<0.05).But there was no statistical difference between the two groups(paired 0.065).There was no significant difference in Irisin between the two groups at baseline,but increased significantly at 52 weeks after treatment.The change of Irisin was more significant in the exenatide group.Compared with the baseline,the Irisin of the two groups was 26.01±7.86 vs 24.91 ±8.65,respectively,but there was no significant difference between the two groups(p=0.665).6.There was no difference in baseline eGFR between the two groups.From 4 weeks after enrollment,eGFR in both groups decreased slightly compared with the baseline(exenatide group-0.44ml/min.1.73 m2,insulin group-3.06ml/min.1.73 m2),but there was no statistical difference.After 28 weeks of treatment,eGFR increased gradually in exenatide group,while eGFR decreased slowly in insulin group.From 40 weeks to 52 weeks after treatment,the values of the two groups and the baseline were written and whether there was statistical significance.At 40 and 52 weeks,there was a significant difference in the decrease of eGFR between the two groups compared with the baseline(p=0.0338,p=0.0135).At the end of 52 weeks,the changes of eGFR in the two groups were 0.56ml/min.1.73 m2 in exenatide group and-4.24ml/min.1.73 m2 in insulin group.7.In exenatide group and insulin group,the eGFR of patients with atherosclerosis at baseline decreased significantly,suggesting that the changes of renal function may be related to atherosclerosis.In the patients with atherosclerosis in the exenatide group,the eGFR was significantly improved with the prolongation of treatment time.The eGFR in the patients without atherosclerosis in the exenatide group decreased slightly at the beginning,partially increased after the lowest-3.2591±6.1469ml/1.73kg/m2,at the 28th week,and decreased slightly at the 52nd week compared with the baseline(-0.941±7.0742ml/1.73kg/m2).However,the renal function of the insulin group with and without atherosclerosis at baseline was lower than that in the exenatide group,but there was no significant difference between the two groups.In the patients with improved atherosclerosis in the exenatide group,the eGFR increased gradually with the extension of treatment time,while in the patients with no improvement of atherosclerosis,the eGFR decreased slightly in the early stage,and gradually returned to the baseline level after 4 weeks.However,the eGFR of patients in the insulin group decreased compared with the baseline after 52 weeks of treatment,but there was no significant difference between the two groups.The change of eGFR in insulin group was positively correlated with 8-oxo-gsn.The change of eGFR in exenatide group was negatively correlated with FPG,BMI and HDL.There was no correlation between the changes of eGFR and HbAlc in the two groups at 52 weeks,suggesting that the change of renal function had nothing to do with the improvement of blood glucose.8.Compared with insulin group,after 52 weeks of intervention,the average intima-media thickness of carotid artery decreased significantly in exenatide group(the change value of two groups compared with baseline was-0.97±0.28mm vs 1.08 ±0.25mm,respectively),and there was significant difference between the two groups(p=0.033).In insulin group,carotid IMT was proportional to low density lipoprotein cholesterol(correlation coefficient 0.441)and fibrinogen(correlation coefficient 0.605),suggesting that arteriosclerosis was related to the increase of blood lipids and the activation of inflammatory factors.This relationship was not found in the exenapeptide group.9.Compared with the baseline data,the carotid intima-media thickness of overweight and obese subjects decreased significantly after 52 weeks of exenazeptide treatment(-0.12±0.22 mm),).The carotid intima-media thickness of normal weight subjects increased slightly(0.0062 ±0.25 mm),but there was no significant difference between the two groups(p=0.21).10.After 52 weeks of treatment with exenatide,the intima-media thickness of carotid artery decreased significantly in subjects with atherosclerosis at baseline(-0.13 ±0.22mm),).The intima-media thickness of carotid artery in subjects without atherosclerosis at baseline increased slightly(-0.08±0.23mm),).The intima-media thickness of carotid artery decreased in the atherosclerosis improvement group(-0.19±0.16 mm)and increased in the progress group(0.21±0.12 mm).There was no significant difference in metabolic related indexes between the two groups.Conclusion1.After 52 weeks of treatment with exenatide,the carotid IMT,of patients with type 2 diabetes decreased,and the patients with overweight and obesity and with atherosclerosis at baseline benefited more.This cardiovascular protective effect of anti-atherosclerosis does not depend on the decrease of blood glucose levels,but may be related to the improvement of blood lipids and inflammatory factors.2.The benign effect of exenatide on atherosclerosis in patients with type 2 diabetes may be beneficial to the improvement of renal function. |
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