前列地尔联合利拉鲁肽对T2DM患者肾功能、血管功能及血脂代谢水平的影响
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摘要
目的观察前列地尔联合利拉鲁肽对2型糖尿病(T2DM)患者肾功能、血管功能及血脂代谢水平的影响并探索其机制。方法选取2015年12月—2018年6月辽宁省金秋医院内分泌代谢科收治的2型糖尿病患者96例作为研究对象,按照随机数字表法分为对照组48例和观察组48例。对照组予以饮食指导、适当锻炼以及利拉鲁肽治疗;观察组在对照组基础上给予前列地尔,2组均治疗8周。比较2组患者治疗前后血糖、血脂、C肽、肾功能、血清Vaspin与内抑素(ENS)水平以及血管功能等指标。结果治疗后,2组患者空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA_(1C))、总胆固醇(TC)、三酰甘油(TG)、尿素氮(BUN)、血肌酐(SCr)及24 h尿蛋白均较治疗前下降(P<0.01),且观察组下降幅度大于对照组(t/P=6.762/0.000、 4.695/0.000、6.264/0.000、5.185/0.000、4.221/0.000、3.902/0.000、2.324/0.022、3.769/0.000);2组患者空腹C肽、餐后2 h C肽较治疗前均升高(P<0.01),且观察组高于对照组(t/P=2.088/0.039、8.218/0.000);2组患者血清Vaspin及ENS水平均高于治疗前(P<0.01),且观察组均高于对照组(t/P=9.758/0.000、24.800/0.000);2组患者下肢血管IMT、PSV、狭窄率均低于治疗前(P<0.01),且观察组各指标优于对照组(t/P=8.506/0.000、4.281/0.000、3.552/0.001);2组患者均未发生严重不良反应事件。结论前列地尔联合利拉鲁肽治疗2型糖尿病疗效显著,可有效控制血糖、血脂,改善胰岛β细胞功能,同时有助于改善患者肾功能和血管功能,平衡Vaspin和ENS的表达,具有积极的临床意义。
Objective To observe the curative effect of alprostadil combined with liraglutide on renal and vascular functions and lipid metabolism in patients with T2 DM and explore its mechanism. Methods Ninety-six patients with type 2 diabetes admitted to the Department of Endocrinology and Metabolism, Jinqiu Hospital of Liaoning Province from December2015 to June 2018 were selected as the study subjects. According to the method of random number table, they were divided into control group(48 cases) and observation group(48 cases). The control group was given dietary guidance, proper exercise and liraglutide treatment. The observation group was given alprostadil on the basis of the control group. Both groups were treated for 8 weeks. Blood sugar, blood lipid, C-peptide, renal function, serum levels of Vaspin and ENS and vascular function were compared between the two groups before and after treatment. Results After treatment, fasting blood glucose(FPG), postprandial 2 h blood glucose(2 h PG), glycohemoglobin(HbA1 C), total cholesterol(TC), triglyceride(TG),urea nitrogen(BUN), blood Creatinine(SCr) and 24 h urinary protein were lower than before treatment, and the decrease in the observation group was greater than that in the control group(t/P = 6. 762/0. 000, t/P =4. 695/0.000, t/P = 6. 264/0.000, t/P =5.185/0.000, t/P =4.221/0.000, t/P = 3.902/0.000, t/P= 2.324/0.022, t/P =3.769/0.000); fasting C peptide in 2 groups of patients, 2 h after meal The C-peptide was higher than that before treatment, and the observation group was higher than the control group(t/P = 2.088/0.039, t/P = 8.218/0.000). The serum levels of Vaspin and ENS in the two groups were higher than before treatment. The observation group was higher than the control group(t/P = 9. 758/0.000, t/P =24.800/0.000); the IMT, PSV and stenosis rate of the lower extremity vessels of the two groups were lower than that before treatment, and the indicators of the observation group were better than the observation group. The control group(t/P = 8. 506/0. 000, t/P =4. 281/0. 000, t/P = 3. 552/0. 001); no serious adverse events occurred in the two groups. Conclusion Alprostadil combined with liraglutide in the treatment of type 2 diabetes mellitus has a significant effect. It can effectively control the metabolism of blood glucose and lipid, improve the function of islet beta cells, improve renal and vascular functions, balance the expression of Vaspin and ENS, and has a positive clinical significance.
Objective To observe the curative effect of alprostadil combined with liraglutide on renal and vascular functions and lipid metabolism in patients with T2 DM and explore its mechanism. Methods Ninety-six patients with type 2 diabetes admitted to the Department of Endocrinology and Metabolism, Jinqiu Hospital of Liaoning Province from December2015 to June 2018 were selected as the study subjects. According to the method of random number table, they were divided into control group(48 cases) and observation group(48 cases). The control group was given dietary guidance, proper exercise and liraglutide treatment. The observation group was given alprostadil on the basis of the control group. Both groups were treated for 8 weeks. Blood sugar, blood lipid, C-peptide, renal function, serum levels of Vaspin and ENS and vascular function were compared between the two groups before and after treatment. Results After treatment, fasting blood glucose(FPG), postprandial 2 h blood glucose(2 h PG), glycohemoglobin(HbA1 C), total cholesterol(TC), triglyceride(TG),urea nitrogen(BUN), blood Creatinine(SCr) and 24 h urinary protein were lower than before treatment, and the decrease in the observation group was greater than that in the control group(t/P = 6. 762/0. 000, t/P =4. 695/0.000, t/P = 6. 264/0.000, t/P =5.185/0.000, t/P =4.221/0.000, t/P = 3.902/0.000, t/P= 2.324/0.022, t/P =3.769/0.000); fasting C peptide in 2 groups of patients, 2 h after meal The C-peptide was higher than that before treatment, and the observation group was higher than the control group(t/P = 2.088/0.039, t/P = 8.218/0.000). The serum levels of Vaspin and ENS in the two groups were higher than before treatment. The observation group was higher than the control group(t/P = 9. 758/0.000, t/P =24.800/0.000); the IMT, PSV and stenosis rate of the lower extremity vessels of the two groups were lower than that before treatment, and the indicators of the observation group were better than the observation group. The control group(t/P = 8. 506/0. 000, t/P =4. 281/0. 000, t/P = 3. 552/0. 001); no serious adverse events occurred in the two groups. Conclusion Alprostadil combined with liraglutide in the treatment of type 2 diabetes mellitus has a significant effect. It can effectively control the metabolism of blood glucose and lipid, improve the function of islet beta cells, improve renal and vascular functions, balance the expression of Vaspin and ENS, and has a positive clinical significance.
引文
[1]Alexandra KW, Jürgen H, Giovanni P. Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus[J]. Endocrine Reviews, 2016, 37(3):278-316. DOI:10.1210/er. 2015-1137.
[2] Leahy JL. Pathogenesis of Type 2 Diabetes Mellitus[J]. Archives of Medical Research,2005,36(3):197-209.
[3] Wei W, An XR, Jin SJ,et al. Inhibition of insulin resistance by PGE1 via autophagy-dependent FGF21 pathway in diabetic nephropathy[J]. Scientific Reports, 2018,8(1):9. DOI:10.1038/s41598-017-18427-2.
[4] Yang W, Li Y, Tian T, et al. Serum vaspin concentration in elderly patients with type 2 diabetes mellitus and macrovascular complications[J]. Bmc Endocrine Disorders, 2017, 17(1):67. DOI:10.1186/s12902-017-0216-0.
[5] Watorek E, Paprocka M, Du D, et al. Endostatin and vascular endothelial growth factor:potential regulators of endothelial progenitor cell number in chronic kidney disease[J]. Polskie Archiwum Medycyny Wewntrznej, 2011, 121(9):296-301. DOI:10.1371/journal.pmed. 1000388.
[6]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2017年版)[J].中华糖尿病杂志,2018,10(1):4-67. DOI:10.3760/cma. j. issn. 1674-5809.2018.01.002.
[7] European Carotid Surgery Trialists'Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis:final results of the MRC European Carotid Surgery Trial(ECST)[J].Lancet 1998,351(9113):1379-1387. DOI:10. 1016/S0140-6736(97)09292-1.
[8]汪会琴,胡如英,武海滨,等.2型糖尿病报告发病率研究进展[J].浙江预防医学,2016,28(1):37-39.(下转567页)(上接562页)
[9] Todd JF, Wilding JP, Edwards CM, et al. Glucagon-like peptide-1(GLP-1):a trial of treatment in non-insulin-dependent diabetes mellitus[J]. European Journal of Clinical Investigation, 2015, 27(6):533-536. DOI:10.1046/j. 1365-2362.1997.1490691. X.
[10] Srinivas NR. Prostaglandin El therapy with alprostadil and risk reduction in early hepatic cellular carcinoma after liver transplantation[J]. Alimentary Pharmacology&Therapeutics, 2016, 43(I):173-174. DOI:10.1111/apt. 13444.
[11] Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists:a review of head-to-head clinical studies[J]. Ther Adv Endocrinol Metab,2015, 6(1):19-28. DOI:10.1177/2042018814559725.
[12] Sun YM, Su Y, Li J, et al. Recent advances in understanding the biochemical and molecular mechanism of diabetic nephropathy[J].Biochem Biophys Res Commun, 2013, 433(4):359-361. DOI:10.1016/j. bbrc.2013.02.120.
[13]álvarez-Villalobos NA, Trevi o-Alvarez AM, Gonzalez-González JG.Liraglutide and cardiovascular outcomes in type 2 diabetes[J]. N Engl J Med, 2016, 375(18):1797-1798. DOI:10. 1056/NEJMc1611289.
[14]邹汶兵.前列地尔联合福辛普利治疗糖尿病肾病蛋白尿的临床疗效及安全性评价[J].中国临床药理学杂志,2016, 32(1):18-20. DOI:10.13699/j.cnki. 1001-6821.2016.01.006.
[15]李庆,宋学君,李志军.血必净联合前列地尔治疗糖尿病肾病的临床疗效观察[J].中国中西医结合急救杂志,2016, 23(3):291-293. DOI:10. 3969/j. issn. 1008-9691.2016.03.017.
[16] Hida K, Wada J, Zhang H, et al. Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats[J]. Journal of Lipid Research, 2000, 41(10):1615-1622. DOI:10.1016/j. femsyr. 2004.02.004.
[17]熊丽萍,董勇.红花黄色素注射液治疗2型糖尿病早期视网膜病变的临床研究[J].世界临床药物,2014, 35(4):206-209.
[2] Leahy JL. Pathogenesis of Type 2 Diabetes Mellitus[J]. Archives of Medical Research,2005,36(3):197-209.
[3] Wei W, An XR, Jin SJ,et al. Inhibition of insulin resistance by PGE1 via autophagy-dependent FGF21 pathway in diabetic nephropathy[J]. Scientific Reports, 2018,8(1):9. DOI:10.1038/s41598-017-18427-2.
[4] Yang W, Li Y, Tian T, et al. Serum vaspin concentration in elderly patients with type 2 diabetes mellitus and macrovascular complications[J]. Bmc Endocrine Disorders, 2017, 17(1):67. DOI:10.1186/s12902-017-0216-0.
[5] Watorek E, Paprocka M, Du D, et al. Endostatin and vascular endothelial growth factor:potential regulators of endothelial progenitor cell number in chronic kidney disease[J]. Polskie Archiwum Medycyny Wewntrznej, 2011, 121(9):296-301. DOI:10.1371/journal.pmed. 1000388.
[6]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2017年版)[J].中华糖尿病杂志,2018,10(1):4-67. DOI:10.3760/cma. j. issn. 1674-5809.2018.01.002.
[7] European Carotid Surgery Trialists'Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis:final results of the MRC European Carotid Surgery Trial(ECST)[J].Lancet 1998,351(9113):1379-1387. DOI:10. 1016/S0140-6736(97)09292-1.
[8]汪会琴,胡如英,武海滨,等.2型糖尿病报告发病率研究进展[J].浙江预防医学,2016,28(1):37-39.(下转567页)(上接562页)
[9] Todd JF, Wilding JP, Edwards CM, et al. Glucagon-like peptide-1(GLP-1):a trial of treatment in non-insulin-dependent diabetes mellitus[J]. European Journal of Clinical Investigation, 2015, 27(6):533-536. DOI:10.1046/j. 1365-2362.1997.1490691. X.
[10] Srinivas NR. Prostaglandin El therapy with alprostadil and risk reduction in early hepatic cellular carcinoma after liver transplantation[J]. Alimentary Pharmacology&Therapeutics, 2016, 43(I):173-174. DOI:10.1111/apt. 13444.
[11] Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists:a review of head-to-head clinical studies[J]. Ther Adv Endocrinol Metab,2015, 6(1):19-28. DOI:10.1177/2042018814559725.
[12] Sun YM, Su Y, Li J, et al. Recent advances in understanding the biochemical and molecular mechanism of diabetic nephropathy[J].Biochem Biophys Res Commun, 2013, 433(4):359-361. DOI:10.1016/j. bbrc.2013.02.120.
[13]álvarez-Villalobos NA, Trevi o-Alvarez AM, Gonzalez-González JG.Liraglutide and cardiovascular outcomes in type 2 diabetes[J]. N Engl J Med, 2016, 375(18):1797-1798. DOI:10. 1056/NEJMc1611289.
[14]邹汶兵.前列地尔联合福辛普利治疗糖尿病肾病蛋白尿的临床疗效及安全性评价[J].中国临床药理学杂志,2016, 32(1):18-20. DOI:10.13699/j.cnki. 1001-6821.2016.01.006.
[15]李庆,宋学君,李志军.血必净联合前列地尔治疗糖尿病肾病的临床疗效观察[J].中国中西医结合急救杂志,2016, 23(3):291-293. DOI:10. 3969/j. issn. 1008-9691.2016.03.017.
[16] Hida K, Wada J, Zhang H, et al. Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats[J]. Journal of Lipid Research, 2000, 41(10):1615-1622. DOI:10.1016/j. femsyr. 2004.02.004.
[17]熊丽萍,董勇.红花黄色素注射液治疗2型糖尿病早期视网膜病变的临床研究[J].世界临床药物,2014, 35(4):206-209.