关键词: 糖尿病, 2型；艾塞那肽；胰岛素；纤维蛋白原；超敏C反应蛋白；白介素6；肿瘤坏死因子α

Abstract: Background　One in twelve deaths in adults can be attributed to diabetes.Diabetic patients have significantly increased blood lipid and inflammatory markers.Moreover，hyperlipidemia，hyperglycemia and elevated inflammatory markers often increase the risk of cardiovascular disease.Objective　To investigate the effect of exenatide combined with insulin on fibrinogen（FIB），high-sensitivity C-reactive protein（hs-CRP），interleukin-6（IL-6） and tumor necrosis factor alpha（TNF-α） in patients with type 2 diabetes with poor glycemic control.Methods　A total of 193 outpatients and inpatients with T2DM were recruited from Department of Endocrinology，Affiliated Hospital of Xuzhou Medical University from June 2016 to June 2018，and were randomized into exenatide group（n=98） and insulin group（n=95）.All patients continued their previous diet，exercise，and oral medication.Besides，the exenatide group additionally took exenatide，and the insulin dose was temporarily reduced by 30%，then was adjusted according to blood glucose later.The insulin group only adjusted the insulin dose based on the blood glucose level.After 6 months of treatment，hypoglycemic effects and changes of FIB，hs-CRP，IL-6 and TNF-α were compared between the two groups.Multiple stepwise linear regression analysis was used to analyze the influencing factors of inflammatory markers.Results　FPG，2 hPG，HOMA-IR，HbA1c，TG，TC，LDL-C，hs-CRP，IL-6 and TNF-α were all decreased in both groups after treatment（P<0.05），whereas HOMA-IR，hs-CRP，IL-6 and TNF-α in exenatide group were significantly lower than those in the insulin group（P<0.05）.In the exenatide group，mean body weight，body mass index（BMI），waist circumference（WC） and daily insulin dosage were also decreased as compared with baseline（P<0.05），but the difference of FIB was not significant compared with the pre-treatment（P>0.05）.In the insulin group，mean body weight，BMI，WC and daily insulin dosage were increased as compared with baseline（P<0.05），but the difference of FIB was not significant（P>0.05）.The difference of pre- and post-treatment ΔFIB was positively correlated with ΔWC，Δbody weight，ΔBMI，and ΔHOMA-IR（r=0.269-0.423，P<0.05）.Δhs-CRP was positively correlated with ΔWC and ΔHOMA-IR（r=0.223-0.515，P<0.05）.ΔIL-6 and ΔTNF-α were positively correlated with ΔWC（r=0.215-0.379，P<0.05）.Multiple stepwise linear regression analysis showed that ΔBMI and ΔHOMA-IR were the influencing factors of ΔFIB，and ΔWC was the influencing factor of Δhs-CRP，ΔIL-6 and ΔTNF-α（P<0.05）.Conclusion　Exenatide with insulin treatment may achieve similar hypoglycemic effect as high-dose insulin，but is superior to the latter in reducing body weight，BMI，WC，insulin dosage，insulin resistance，as well as subclinical inflammation markers.

Key words: Diabetes mellitus, type 2；Exenatide；Insulin；Fibrinogen；Hypersensitive C-reactive protein；Interleukin-6；Tumor necrosis factor-α