达格列净联合利拉鲁肽强化降糖治疗对二甲双胍治疗失效的2型糖尿病患者胰岛素抵抗、游离脂肪酸及过氧化物酶体激增物激活受体γ影响的研究被引量：66

Effects of Dapagliflozin combined with Liraglutide on insulin resistance,FFA and PPARγ in T2DM treated with Metformin

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摘要目的探讨达格列净联合利拉鲁肽强化降糖治疗对T2DM患者IR、FFA及PPARγ的影响。方法选取2018年12月至2022年1月于我院内分泌科收治的二甲双胍治疗失效的T2DM患者120例,分为达格列净治疗组(Dap)及达格列净联合利拉鲁肽治疗组(Dap+Lir),每组各60例。比较两组血糖、血脂、单核细胞趋化蛋白1(MCP-1)、血管细胞黏附分子1(VCAM-1)、分泌型卷曲相关蛋白5(SFRP5)、γ-谷氨酰转肽酶(γ-GT)、过氧化物酶体增殖物激活受体γ(PPAR γ)、FFA、HOMA-IR及不良反应。结果治疗后Dap+Lir组VCAM-1、γ-GT、MCP-1低于Dap组[(27.49±8.12)vs(35.68±8.21)ng/L,(21.84±4.48)vs(33.85±4.18)U/L,(37.59±3.45)vs(68.51±3.51)μg/L,P<0.05],SFRP5高于Dap组[(5.54±0.32)vs(3.28±0.22)μg/L,P<0.05];治疗后1、2、3及6个月时,Dap+Lir组FFA低于Dap组[(13.62±1.03)vs(15.68±0.89)ng/ml,(10.27±0.66)vs(12.63±0.71)ng/ml,(9.84±0.31)vs(10.32±0.29)ng/ml,(9.76±0.27)vs(10.13±0.33)ng/ml,P<0.05],PPARγ高于Dap组[(1226.18±98.48)vs(1004.75±83.99)pg/ml,(1374.98±95.48)vs(1219.74±90.29)pg/ml,(1387.39±92.31)vs(1293.48±96.64)pg/ml,(2584.39±99.48)vs(2212.03±93.84)pg/ml,P<0.05]。结论达格列净联合利拉鲁肽强化降糖治疗可有效抑制二甲双胍治疗失效的T2DM患者IR,改善FFA、PPARγ水平。 Objective To investigate the effects of Dapagliflozin combined with Liraglutide for intensive hypoglycemic therapy on insulin resistance(IR),FFA and PPARγ in patients with type 2 diabetes mellitus(T2DM).Methods 120 T2DM patients who did not reach the target after Metformin treatment were divided into Dapagliflozin group(Dap,n=60)and Dapagliflozin combined with liraglutide group(Dap+Lir,n=60)from December 2018 to January 2022. The levels of blood glucose,lipids,MCP-1,VCAM-1,SFRP5,γ-GT,PPARγ and FFA were measured and HOMA-IR was calculated.Results Compared with Dap group,the levels of VCAM-1,γ-GT and MCP-1 were lower in DAP+Lir group[(27. 49±8. 12)vs(35. 68±8. 21)ng/L,(21. 84±4. 48)vs(33. 85±4. 18)U/L,(37. 59±3. 45)vs(68. 51±3. 51)μg/L,P<0. 05],and SFRP5 was higher[(5. 54±0. 32)vs(3. 28±0. 22)μg/L,P<0. 05]. At 1,2,3 and 6months after treatment,FFA was lower in DAP+Lir group than that in DAP group[(13. 62±1. 03)vs (15. 68±0. 89)ng/ml,(10. 27±0. 66)vs(12. 63±0. 71)ng/ml,(9. 84±0. 31)vs(10. 32±0. 29)ng/ml,(9. 76 ± 0. 27)vs(10. 13 ± 0. 33)ng/ml,P<0. 05],and PPARγ was higher[(1226. 18 ± 98. 48)vs(1004. 75 ± 83. 99)pg/ml,(1374. 98 ± 95. 48)vs(1219. 74 ± 90. 29)pg/ml,(1387. 39 ± 92. 31)vs(1293. 48±96. 64)pg/ml,(2584. 39±99. 48)vs(2212. 03±93. 84)pg/ml,P<0. 05].Conclusion Dapagliflozin combined with Liraglutide could not only achieve intensive hypoglycemic therapy but also effectively improve IR in T2DM patients who did not reach the glucose target after Metformin treatment.