首页|利拉鲁肽、双歧杆菌三联活菌胶囊用于胰岛素+口服药疗效不佳的肥胖2型糖尿病患者的疗效观察

利拉鲁肽、双歧杆菌三联活菌胶囊用于胰岛素+口服药疗效不佳的肥胖2型糖尿病患者的疗效观察

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目的:基于血糖漂移、脂肪细胞炎症反应、磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)通路,探讨利拉鲁肽+双歧杆菌三联活菌胶囊用于胰岛素+口服药疗效不佳的肥胖 2 型糖尿病(T2DM)患者的效果与机制。方法:前瞻性选取 2022 年 6 月至 2023 年6 月该院收治的胰岛素+口服药疗效不佳的肥胖T2DM患者980例,采用单盲法,以随机数字表法分为利拉鲁肽组、联合组,各490例。两组患者均给予胰岛素+口服药;在此基础上,利拉鲁肽组患者给予利拉鲁肽,联合组患者给予利拉鲁肽+双歧杆菌三联活菌胶囊。比较两组患者的空腹血糖、餐后 2 h血糖(2 hBG)、糖化血红蛋白(HbA1c)、体重指数(BMI)、胰岛素抵抗指数(HOMA-IR)、C肽、血糖漂移、平均血糖波动幅度(MAGE)、血糖曲线下面积(AUCPG)、脂肪细胞炎症反应指标[分泌型卷曲相关蛋白 5(sfrp5)、内脂素(Visfatin)、趋化素(Chemerin)、肿瘤坏死因子α(TNF-α)和白细胞介素 6(IL-6)]、PI3K/Akt通路[磷酸化PI3K(P-PI3K)、磷酸化Akt(P-Akt)和核因子κB(NF-κB)]及安全性。结果:治疗 4、12 周后,联合组患者空腹血糖、2 hBG和HbA1 c水平低于利拉鲁肽组,BMI、HOMA-IR低于利拉鲁肽组,C肽水平高于利拉鲁肽组,血糖漂移系数、血糖漂移最大幅度、MAGE和AUCPG>7。8 mmol/L 低于利拉鲁肽组,sfrp5 水平高于利拉鲁肽组,Visfatin、Chemerin、TNF-α和IL-6水平低于利拉鲁肽组,P-PI3K、P-Akt水平高于利拉鲁肽组,NF-κB水平低于利拉鲁肽组,上述差异均有统计学意义(P<0。05)。利拉鲁肽组患者的不良反应发生率为 1。22%(6/490),与联合组的 0。61%(3/490)相比,差异无统计学意义(P>0。05)。结论:利拉鲁肽+双歧杆菌三联活菌胶囊用于胰岛素+口服药疗效不佳的肥胖T2DM患者,能发挥降糖和减重双重作用,改善患者血糖漂移、胰岛素抵抗和胰岛β细胞功能,抑制脂肪细胞炎症反应,调控PI3K/Akt通路,安全可靠,或可作为胰岛素+口服药疗效不佳的肥胖T2DM患者的一个治疗选择。
Efficacy of Liraglutide and Bifidobacterium Triple Viable Capsules in the Treatment of Obese Type 2 Diabetes Mellitus with Poor Efficacy of Insulin+Oral Drugs
OBJECTIVE:To probe into the efficacy and mechanism of liraglutide+Bifidobacterium triple viable capsules in the treatment of obese type 2 diabetes mellitus(T2DM)with poor efficacy of insulin+oral drugs based on blood glucose excursion,adipocyte inflammatory reaction and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway.METHODS:A total of 980 patients with obese T2DM with poor efficacy of insulin+oral medication admitted to our hospital from Jun.2022 to Jun.2023 were prospectively selected,which were divided into liraglutide group and combination group via single-blind method and random number table method,with 490 cases in each group.Both groups were given insulin+oral medication;on that basis,the liraglutide group received liraglutide,and combination group was given liraglutide+Bifidobacterium triple viable capsule.The fasting blood glucose,2 h postprandial blood glucose(2 hBG),glycated hemoglobin(HbA1c),body mass index(BMI),Insulin resistance index(HOMA-IR),C-peptide,glucose excursion,mean amplitude of glucose excursion(MAGE),area under the curve for blood glucose(AUCPG),adipocyte inflammatory response[secreted frizzled-related protein 5(sfrp5),Visfatin,Chemerin,tumor necrosis factor α(TNF-α),interleukin6(IL-6)],PI3K/Akt pathway[phosphorylated PI3K(P-PI3K),phosphorylated Akt(P-Akt)and nuclear factor-κB(NF-κB)]and safety were compared between two groups.RESULTS:After 4 and 12 weeks of treatment,the fasting blood glucose,2 hBG and HbA1c levels of the combination group were lower than those of the liraglutide group,the BMI and HOMA-IR of the combination group were lower than those of the liraglutide group,the C-peptide of the combination group was higher than that of the liraglutide group,the glucose excursion coefficient,amplitude peak of glucose excursion,MAGE and AUCPG>7.8 mmol/L of the combination group were lower than those of the liraglutide group,the sfrp5 of the combination group was higher than that of the liraglutide group,the Visfatin,Chemerin,TNF-α and IL-6 levels of the combination group were lower than those of the liraglutide group,the P-PI3K and P-Akt of the combination group were higher than those of the liraglutide group,the NF-κB of the combination group was lower than that of the liraglutide group,all of the above differences were statistically significant(P<0.05).The incidence of adverse drug reaction of the liraglutide group was 1.22%(6/490),compared with 0.61%(3/490)of the combination group,the difference was not statistically significant(P>0.05).CONCLUSIONS:The application of liraglutide+Bifidobacterium triple viable capsules on obese T2DM with poor efficacy of insulin+oral drugs is safe and reliable,which can play the dual role of glucose-reducing and weight-loss,improve patients'glucose excursion,insulin resistance and pancreatic β-cell function,inhibit adipocyte inflammatory response and regulate PI3K/Akt pathway,and might be used as a therapeutic option for obese T2DM patients with poor efficacy of insulin+oral drugs.

Glucose excursionAdipocytesPI3K/Akt pathwayLiraglutideBifidobacterium triple viable capsuleObesityType 2 diabetes mellitus

刘玉斌、王晓蕴、马凌云

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河北省沧州中西医结合医院内分泌糖尿病科,河北 沧州 062650

血糖漂移 脂肪细胞 PI3K/Akt通路 利拉鲁肽 双歧杆菌三联活菌胶囊 肥胖 2型糖尿病

2021年度中医药类科研计划课题

2021351

2024

中国医院用药评价与分析
中国医药生物技术协会,中国药房杂志社

中国医院用药评价与分析

CSTPCD
影响因子:1.142
ISSN:1672-2124
年,卷(期):2024.24(7)