西格列汀在糖尿病周围神经病变中的效果
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摘要
目的探讨西格列汀在糖尿病周围神经病变(DPN)中的治疗效果。方法选取DPN患者36例,给予西格列汀治疗6个月。比较治疗前后血糖、血脂、多伦多临床评分系统(TCSS)评分及神经传导速度(NCV)变化情况。结果应用西格列汀治疗24周后,DPN患者空腹血糖及餐后2 h血糖水平下降(P<0.01),糖化血红蛋白水平降低(P<0.001),TCSS评分下降(P<0.001),NCV增加(P<0.001)。结论西格列汀治疗可改善DPN患者临床症状及NCV,在DPN的治疗中具有良好的应用价值。
ObjectiveTo investigate the therapeutic effect of sitagliptin on diabetic peripheral neuropathy(DPN).Methods A total of 36 patients w ith DPN w ere treated w ith sitagliptin for 6 months.The changes of blood sugar,blood lipid,Toronto Clinical Scoring System(TCSS)score and nerve conduction velocity(NCV)w ere compared before and after treatment.Results After 24 w eeks of treatment w ith sitagliptin,fasting blood glucose and 2 h postprandial blood glucose levels in patients w ith DPN decreased(P<0.01);the hemoglobin A1C level decreased(P<0.001);the TCSS score decreased(P<0.001);and the NCV increased(P<0.001).Conclusion Sitagliptin can improve the clinical symptoms and NCV of DPN patients,and it has a good application value in the treatment of DPN.
ObjectiveTo investigate the therapeutic effect of sitagliptin on diabetic peripheral neuropathy(DPN).Methods A total of 36 patients w ith DPN w ere treated w ith sitagliptin for 6 months.The changes of blood sugar,blood lipid,Toronto Clinical Scoring System(TCSS)score and nerve conduction velocity(NCV)w ere compared before and after treatment.Results After 24 w eeks of treatment w ith sitagliptin,fasting blood glucose and 2 h postprandial blood glucose levels in patients w ith DPN decreased(P<0.01);the hemoglobin A1C level decreased(P<0.001);the TCSS score decreased(P<0.001);and the NCV increased(P<0.001).Conclusion Sitagliptin can improve the clinical symptoms and NCV of DPN patients,and it has a good application value in the treatment of DPN.
引文
[1]温旭东, 汤玮, 刘志民. 胰高血糖素样肽-1缓解糖尿病周围神经病变的机制研究进展[J].第二军医大学学报, 2011, 32(3):329-333.WEN Xudong, TANG Wei, LIU Zhimin. Glucagon-like peptide-1 alleviating peripheral neuropathy in diabetic patients:advance in mechanism[J]. Academic Journal of Second Military medical University, 2011, 32(3):329-333.
[2]Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation[J]. Diabet Med, 1998, 15(7):539-553.
[3]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.
[4]陆游, 陆颖理. 糖尿病性周围神经病变发生机制的研究进展[J]. 上海交通大学学报(医学版), 2017, 37(10):1441-1445. LU You, LU Yingli. Progress in pathogenesis of diabetic peripheral neuropathy[J]. Journal of Shanghai Jiaotong University(Medical Science), 2017, 37(10):1441-1445.
[5]Javed S, Alam U, Malik RA. Treating diabetic neuropathy:present strategies and emerging solutions[J]. Rev Diabet Stud, 2015, 12(1/2):63-83.
[6]Malik RA. Why are there no good treatments for diabetic neuropathy?[J]. Lancet Diabetes Endocrinol, 2014, 2(8):607-609.
[7]Winkler G. Pleiotropic effects of incretins and antidiabetic drugs with incretine mechanism[J]. Orv Hetil, 2013, 154(7):248-255.
[8]Shen T, Xu BL, Lei T, et al. Sitagliptin reduces insulin resistance and improves rat liver steatosis via the SIRT1/AMPKα pathway[J]. Exp Ther Med, 2018, 16(4):3121-3128.
[9]Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1[J]. Cell Metab, 2018, 27(4):740-756.
[10]Cai XL, Gao XY, Yang WJ, et al. DPP-4 inhibitor treatment in Chinese type 2 diabetes patients: a meta-analysis[J]. Diabetes Technol Ther, 2016, 18(12):784-793.
[11]H?lscher C. The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer?s disease[J]. Alzheimers Dement, 2014, 10(1 Suppl):S47-S54.
[12]Tai JJ, Liu WZ, Li YW, et al. Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer?s disease[J]. Brain Res, 2018, 1678:64-74. doi:10.1016/j.brainres.2017.10.012.
[13]H?lscher C. The role of GLP-1 in neuronal activity and neurodegeneration[J]. Vitam Horm, 2010, 84:331-354. doi:10.1016/B978-0-12-381517-0.00013-8.
[14]Feng P, Zhang XJ, Li DF, et al. Two novel dual GLP-1/GIP receptor agonists are neuroprotective in the MPTP mouse model of Parkinson?s disease[J]. Neuropharmacology, 2018, 133:385-394. doi:10.1016/j.neuropharm.2018.02.012.
[15]Cai XS, Tan ZG, Li JJ, et al. Glucagon-like peptide-1 (GLP-1) treatment ameliorates cognitive impairment by attenuating arc expression in type 2 diabetic rats[J]. Med Sci Monit, 2017, 23:4334-4342. doi:10.12659/MSM.903252.
[16]Liu WJ, Jin HY, Lee KA, et al. Neuroprotective effect of the glucagon-like peptide-1 receptor agonist, synthetic exendin-4, in streptozotocin-induced diabetic rats[J]. Br J Pharmacol, 2011, 164(5):1410-1420.
[17]Ma JJ, Shi M, Zhang XC, et al. GLP-1R agonists ameliorate peripheral nerve dysfunction and inflammation via p38 MAPK/NF-κB signaling pathways in streptozotocin-induced diabetic rats[J]. Int J Mol Med, 2018, 41(5):2977-2985.
[18]Yang CP, Li CI, Liu CS, et al. Variability of fasting plasma glucose increased risks of diabetic polyneuropathy in T2DM[J]. Neurology, 2017, 88(10):944-951.
[19]Selvarajah D, Wilkinson ID, Maxwell M, et al. Magnetic resonance neuroimaging study of brain structural differences in diabetic peripheral neuropathy[J]. Diabetes Care, 2014, 37(6):1681-1688.
[20]Rizzo MR, Barbieri M, Marfella R, et al. Response to Comment on: Rizzo et al. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care 2012;35:2076-2082[J]. Diabetes Care, 2013, 36(1):e13. doi:10.2337/dc12-1436.
[21]赵亚丽. 2型糖尿病使用西格列汀对氧化应激和炎性反应状态的控制及对周围神经病变的影响[J]. 河北医药, 2017, 39(23):3550-3553. ZHAO Yali. Effects of sitagliptin on oxidative stress, inflammatory reactions and peripheral neuropathy of patients with type 2 diabetes mellitus[J]. Hebei Medical Journal, 2017, 39(23):3550-3553.
[22]Heppner KM, Kirigiti M, Secher A, et al. Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain[J]. Endocrinology, 2015, 156(1):255-267.
[23]程茅薇, 顾萍, 马健, 等. 西格列汀对db/db糖尿病小鼠坐骨神经传导速度的影响[J]. 中国全科医学, 2011, 14(18):2055-2058. CHENG Maowei, GU Ping, MA Jian, et al. Effects of sitagliptin on motor nerve conduction velocity of sciatic nerve in db/db mice[J]. Chinese General Practice, 2011, 14(18):2055-2058.
[24]Gong N, Xiao Q, Zhu B, et al. Activation of spinal glucagon-like peptide-1 receptors specifically suppresses pain hypersensitivity[J]. J Neurosci, 2014, 34(15):5322-5334.
[25]Tani S, Ken NG, Hirayama A. Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor, vildagliptin: a pilot study[J]. Am J Cardiovasc Drugs, 2013, 13(6):443-450.
[26]Yoon SA, Han BG, Kim SG, et al. Efficacy, safety and albuminuria-reducing effect of gemigliptin in Korean type 2 diabetes patients with moderate to severe renal impairment: A 12-week, double-blind randomized study (the GUARD Study)[J]. Diabetes Obes Metab, 2017, 19(4):590-598.
[27]Marques C, Mega C, Gon?alves A, et al. Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals[J]. Mediators Inflamm, 2014:538737. doi:10.1155/2014/538737.
[2]Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation[J]. Diabet Med, 1998, 15(7):539-553.
[3]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.
[4]陆游, 陆颖理. 糖尿病性周围神经病变发生机制的研究进展[J]. 上海交通大学学报(医学版), 2017, 37(10):1441-1445. LU You, LU Yingli. Progress in pathogenesis of diabetic peripheral neuropathy[J]. Journal of Shanghai Jiaotong University(Medical Science), 2017, 37(10):1441-1445.
[5]Javed S, Alam U, Malik RA. Treating diabetic neuropathy:present strategies and emerging solutions[J]. Rev Diabet Stud, 2015, 12(1/2):63-83.
[6]Malik RA. Why are there no good treatments for diabetic neuropathy?[J]. Lancet Diabetes Endocrinol, 2014, 2(8):607-609.
[7]Winkler G. Pleiotropic effects of incretins and antidiabetic drugs with incretine mechanism[J]. Orv Hetil, 2013, 154(7):248-255.
[8]Shen T, Xu BL, Lei T, et al. Sitagliptin reduces insulin resistance and improves rat liver steatosis via the SIRT1/AMPKα pathway[J]. Exp Ther Med, 2018, 16(4):3121-3128.
[9]Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1[J]. Cell Metab, 2018, 27(4):740-756.
[10]Cai XL, Gao XY, Yang WJ, et al. DPP-4 inhibitor treatment in Chinese type 2 diabetes patients: a meta-analysis[J]. Diabetes Technol Ther, 2016, 18(12):784-793.
[11]H?lscher C. The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer?s disease[J]. Alzheimers Dement, 2014, 10(1 Suppl):S47-S54.
[12]Tai JJ, Liu WZ, Li YW, et al. Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer?s disease[J]. Brain Res, 2018, 1678:64-74. doi:10.1016/j.brainres.2017.10.012.
[13]H?lscher C. The role of GLP-1 in neuronal activity and neurodegeneration[J]. Vitam Horm, 2010, 84:331-354. doi:10.1016/B978-0-12-381517-0.00013-8.
[14]Feng P, Zhang XJ, Li DF, et al. Two novel dual GLP-1/GIP receptor agonists are neuroprotective in the MPTP mouse model of Parkinson?s disease[J]. Neuropharmacology, 2018, 133:385-394. doi:10.1016/j.neuropharm.2018.02.012.
[15]Cai XS, Tan ZG, Li JJ, et al. Glucagon-like peptide-1 (GLP-1) treatment ameliorates cognitive impairment by attenuating arc expression in type 2 diabetic rats[J]. Med Sci Monit, 2017, 23:4334-4342. doi:10.12659/MSM.903252.
[16]Liu WJ, Jin HY, Lee KA, et al. Neuroprotective effect of the glucagon-like peptide-1 receptor agonist, synthetic exendin-4, in streptozotocin-induced diabetic rats[J]. Br J Pharmacol, 2011, 164(5):1410-1420.
[17]Ma JJ, Shi M, Zhang XC, et al. GLP-1R agonists ameliorate peripheral nerve dysfunction and inflammation via p38 MAPK/NF-κB signaling pathways in streptozotocin-induced diabetic rats[J]. Int J Mol Med, 2018, 41(5):2977-2985.
[18]Yang CP, Li CI, Liu CS, et al. Variability of fasting plasma glucose increased risks of diabetic polyneuropathy in T2DM[J]. Neurology, 2017, 88(10):944-951.
[19]Selvarajah D, Wilkinson ID, Maxwell M, et al. Magnetic resonance neuroimaging study of brain structural differences in diabetic peripheral neuropathy[J]. Diabetes Care, 2014, 37(6):1681-1688.
[20]Rizzo MR, Barbieri M, Marfella R, et al. Response to Comment on: Rizzo et al. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care 2012;35:2076-2082[J]. Diabetes Care, 2013, 36(1):e13. doi:10.2337/dc12-1436.
[21]赵亚丽. 2型糖尿病使用西格列汀对氧化应激和炎性反应状态的控制及对周围神经病变的影响[J]. 河北医药, 2017, 39(23):3550-3553. ZHAO Yali. Effects of sitagliptin on oxidative stress, inflammatory reactions and peripheral neuropathy of patients with type 2 diabetes mellitus[J]. Hebei Medical Journal, 2017, 39(23):3550-3553.
[22]Heppner KM, Kirigiti M, Secher A, et al. Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain[J]. Endocrinology, 2015, 156(1):255-267.
[23]程茅薇, 顾萍, 马健, 等. 西格列汀对db/db糖尿病小鼠坐骨神经传导速度的影响[J]. 中国全科医学, 2011, 14(18):2055-2058. CHENG Maowei, GU Ping, MA Jian, et al. Effects of sitagliptin on motor nerve conduction velocity of sciatic nerve in db/db mice[J]. Chinese General Practice, 2011, 14(18):2055-2058.
[24]Gong N, Xiao Q, Zhu B, et al. Activation of spinal glucagon-like peptide-1 receptors specifically suppresses pain hypersensitivity[J]. J Neurosci, 2014, 34(15):5322-5334.
[25]Tani S, Ken NG, Hirayama A. Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor, vildagliptin: a pilot study[J]. Am J Cardiovasc Drugs, 2013, 13(6):443-450.
[26]Yoon SA, Han BG, Kim SG, et al. Efficacy, safety and albuminuria-reducing effect of gemigliptin in Korean type 2 diabetes patients with moderate to severe renal impairment: A 12-week, double-blind randomized study (the GUARD Study)[J]. Diabetes Obes Metab, 2017, 19(4):590-598.
[27]Marques C, Mega C, Gon?alves A, et al. Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals[J]. Mediators Inflamm, 2014:538737. doi:10.1155/2014/538737.