摘要
目的:探讨吡格列酮联合利拉鲁肽治疗肥胖2型糖尿病(T2DM)的疗效,并分析其对胰岛功能、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体的影响.方法:回顾性选取2021年7月至2023年4月肥胖T2DM患者116例,按照随机数字表法分为对照组(利拉鲁肽,58例)、研究组(吡格列酮联合利拉鲁肽,58例),连续治疗3个月.比较两组治疗效果.采集两组治疗前、治疗3个月后血液样本,采用XC8001全自动生化分析仪检测糖脂代谢.采用免疫层析法检测空腹胰岛素(试剂盒购自上海康朗生物公司),计算胰岛素抵抗指数(HOMA-IR)、胰岛素β细胞功能指数(HOMA-β).实时荧光定量聚合酶链反应(qRT-PCR)检测NLRP3炎性小体指标水平.采用ELISA法检测两组治疗前后血清白细胞介素-6(IL-6)、白细胞介素-β(IL-1β)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)水平.比较两组不良反应.、结果:研究组总有效率为94.83％,高于对照组的81.03％(x2=5.199,P=0.023);治疗3个月后,研究组空腹血糖(FBG)、餐后2h血糖(2 hPG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固 醇(LDL-C)水平分别为(4.82±0.56)mmoL/L、(11.24±2.04)mmoL/L、(5.47±0.61)％、(3.16±0.33)mmoL/L、(1.31±0.30)mmoL/L、(2.01±0.34)mmoL/L,均低于对照组的(5.57±0.74)mmoL/L、(13.07±2.16)mmoL/L、(6.73±0.68)％、(3.89±0.54)mmoL/L、(1.82±0.35)mmoL/L、(2.39±0.42)mmoL/L(P＜0.05);治疗3个月后,研究组高密度脂蛋白胆固醇(HDL-C)水平(1.38±0.22)mmoL/L高于对照组的(1.14±0.19)mmoL/L(P＜0.05);治疗3个月后,研究组胰岛素抵抗指数(HOMA-IR)(2.16±0.37)低于对照组的(2.58±0.46),研究组胰岛素β细胞功能指数(HOMA-β)(48.20±6.03)高于对照组的[(42.81±5.54),(P＜0.05)];治疗 3 个月后,研究组 PBMC 中NLRP3 mRNA、凋亡相关斑点样蛋白(ASC)mRNA、半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)mRNA表达量分别为(1.03±0.32)、(1.11±0.28)、(1.09±0.41),低于对照组[(1.65±0.38)、(1.57±0.30)、(1.72±0.49),(P＜0.05)];治疗3个月后,研究组血清白细胞介素-6(IL-6)、白细胞介素-β(IL-1β)、肿瘤坏死 因子-α(TNF-α)、C 反应蛋白(CRP)水平分别为(8.55±2.13)pg/mL、(35.24±5.93)ng/L、(11.42±2.64)ng/L、(1.08±0.31)mg/L,低于对照组的(11.47±2.68)pg/mL、(42.53±7.06)ng/L、(15.03±3.18)ng/L、(1.46±0.44)mg/L(P＜0.05);两组不良反应比较无明显差异(P＞0.05).结论:吡格列酮联合利拉鲁肽治疗肥胖T2DM的疗效确切且具有一定安全性,可促进糖脂代谢、胰岛功能改善,抑制炎性反应,可能与抑制NLRP3炎性小体活化有关.
Abstract
Objective:To investigate the efficacy of pioglitazone combined with liraglutide in the treat-ment of obese type 2 diabetes mellitus(T2DM),and to analyze the effects of pioglitazone combined with lira-glutide on islet function and the inflammasome of nucleotide-binding oligomerized domain-like receptor pro-tein 3(NLRP3).Methods:A retrospective study was conducted on 116 obese patients with type 2 diabetes mellitus(T2DM)from July 2021 to April 2023.The patients were randomly divided into a control group(li-raglutide,58 cases)and a study group(pioglitazone combined with liraglutide,58 cases)according to a ran-dom number table method,and treated continuously for 3 months.The therapeutic efficacy of the two groups was compared.Blood samples were collected before and after treatment for 3 months in both groups,and the blood glucose and lipid metabolism were detected using an XC8001 automatic biochemical analyzer.The fast-ing insulin level was detected using immunochromatography(the kit was purchased from Shanghai Kanglang Biotechnology Co.,Ltd.),and the insulin resistance index(HOMA-IR)and insulin beta cell function index(HOMA-β)were calculated.The level of NLRP3 inflammatory body index was detected using real-time quantitative polymerase chain reaction(qRT-PCR).The levels of serum interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and C-reactive protein(CRP)were detected using ELISA before and after treatment in both groups.The adverse reactions of the two groups were compared.Results:The total effective rate in the study group was 94.83％,which was higher than the 81.03％in the control group(x2=5.199,P=0.023).Three months after treatment,The levels of fasting blood glucose(FBG),2 h postprandial glucose(2 hPG),glycated hemoglobin(HbAlc),total cholesterol(TC),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C)in the study group were(4.82±0.56)mmol/L,(11.24±2.04)mmol/L and(5.47±0.61)％,(3.16±0.33)mmol/L,(1.31±0.30)mmol/L,(2.01±0.34)mmol/L,Were lower than(5.57±0.74)mmol/L,(13.07±2.16)mmol/L,(6.73±0.68)％,(3.89±0.54)mmol/L,(1.82±0.35)mmol/L,(2.39±0.42)mmol/L in control group(P＜0.05).After 3 months of treatment,the level of high-density lipoprotein cholesterol(HDL-C)in the study group(1.38±0.22)mmol/L was higher than that in the control group(1.14±0.19)mmol/L(P＜0.05).After 3 months of treat-ment,the insulin resistance index(HOMA-IR)of the study group(2.16±0.37)was lower than that of the control group(2.58±0.46),and the insulin beta cell function index(HOMA-β)of the study group(48.20±6.03)was higher than that of the control group[(42.81±5.54),(P＜0.05)].After 3 months of treat-ment,the expression levels of NLRP3 mRNA,apoptosis-related speck-like protein(ASC)mRNA and Caspase-1 mRNA in PBMC of the study group were(1.03±0.32),(1.11±0.28)and(1.09±0.41),re-spectively,lower than control group[(1.65±0.38),(1.57±0.30),(1.72±0.49),(P＜0.05)];Three months after treatment,Serum levels of interleukin-6(IL-6),interleukin-β(IL-1β),tumor necrosis fac-tor-α(TNF-α)and C-reactive protein(CRP)in the study group were(8.55±2.13)pg/mL,(35.24±5.93)ng/L,(11.42±2.64)ng/L,(1.0 8±0.31 mg/L was lower than that of control group(11.47±2.68)pg/mL,(42.53±7.06)ng/L,(15.03±3.18)ng/L,(1.46±0.44)mg/L(P＜0.05).There was no signif-icant difference in adverse reactions between the two groups(P＞0.05).Conclusion:Pioglitazone combined with liraglutide is effective and safe in the treatment of obese T2DM.It can correct the disorder of glucose and lipid metabolism,promote the improvement of islet function,and inhibit inflammatory response,which may be related to inhibiting the activation of NLRP3 inflammasome.
基金项目
江苏省新药研究与临床药学重点实验室(KFKT-2110)
维普
万方数据