维生素D联合西格列汀对2型糖尿病肾病患者尿蛋白水平、骨密度和骨代谢的影响
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摘要
目的探讨维生素D联合西格列汀对2型糖尿病肾病患者尿蛋白水平、骨密度和骨代谢的影响。方法选取2016年1月—2018年1月间宁波市鄞州区第二医院收治的114例2型糖尿病肾病患者,随机分为对照组56例和实验组58例。所有患者均给予降糖等常规治疗,在此基础上,对照组给予维生素D治疗,实验组给予维生素D联合西格列汀治疗,比较治疗后2组患者的尿白蛋白排泄率(UAER)、尿β_2-微球蛋白(β_2-MG)、24小时尿白蛋白、骨密度(L_2～L_4、股骨颈、Ward三角区、股骨粗隆区、髋关节)、血钙、血磷、25羟维生素D(25-OH-D_3)、甲状旁腺素(PTH)、骨钙素(BGP)、Ⅰ型前胶原氨基末端前肽(PINP)、Ⅰ型胶原羧基端肽β特殊序列(β-CTX)。结果治疗后实验组患者的UAER、尿β_2-MG和24小时尿白蛋白水平均低于对照组(P<0.05);治疗后实验组患者各检测部位的骨密度均高于对照组(P<0.05);治疗后实验组的血钙高于对照组,血磷显著低于对照组(P<0.05);治疗后实验组的25-OH-D_3和PINP高于对照组(P<0.05),实验组的PTH、BGP和β-CTX低于对照组(P<0.05);对照组和实验组患者的不良反应总发生率分别为8.93%和12.07%(P=0.585)。结论在治疗2型糖尿病肾病中应用维生素D联合西格列汀能有效降低患者的尿蛋白,升高患者的骨密度并改善骨代谢,且安全性较好。
Objective To explore the effect of vitamin D combined with Siglitatin on urinary protein level, bone mineral density and bone metabolism in patients with type 2 diabetic nephropathy. Methods From January 2016 to January 2018, 114 patients with type 2 diabetic nephropathy in our hospital were divided into two groups according to the random number table method, 56 cases in the control group and 58 cases in the experimental group. All patients were given routine treatment such as hypoglycemia. On this basis, the control group was given vitamin D treatment, and the experimental group was given vitamin D combined with Siglitatin treatment. The urinary albumin excretion rate(UAER), urinary beta 2-microglobulin(beta 2-MG), urinary microalbumin(mA1 b), bone mineral density(L_2-L_4, femoral neck, Ward triangle, femoral trochanter, hip joint), serum calcium, phosphorus, 25-hydroxyvitamin D(25-OH-D_3), parathyroid hormone(PTH), bone gla protein(BGP), procollagen type I N propeptide(PINP) and C-terminal telopeptides of type I collagen(β-CTX) were compared between the two groups after treatment. Results After treatment, UAER, urinary beta 2-MG and 24-hour urinary albumin levels in the experimental group were lower than those in the control group(P<0.05). After treatment, the bone mineral density of each detection site in the experimental group was higher than that in the control group(P<0.05). The serum calcium of the experimental group were higher than those of the control group, and the serum phosphorus of the experimental group were lower than those of the control group(P<0.05). After treatment, the levels of 25-OH-D_3 and PINP in the experimental group were significantly higher than those in the control group(P<0.05), and PTH, BGP and beta-CTX in the experimental group were significantly lower than those in the control group(P<0.05). The total incidence of adverse reactions in the control group and the experimental group were 8.93% and 12.07%, respectively, with no significant difference(P=0.585). Conclusion In the treatment of type 2 diabetic nephropathy, vitamin D combined with Siglitatin can effectively reduce urinary protein, increase bone mineral density and improve bone metabolism in patients with better safety.
Objective To explore the effect of vitamin D combined with Siglitatin on urinary protein level, bone mineral density and bone metabolism in patients with type 2 diabetic nephropathy. Methods From January 2016 to January 2018, 114 patients with type 2 diabetic nephropathy in our hospital were divided into two groups according to the random number table method, 56 cases in the control group and 58 cases in the experimental group. All patients were given routine treatment such as hypoglycemia. On this basis, the control group was given vitamin D treatment, and the experimental group was given vitamin D combined with Siglitatin treatment. The urinary albumin excretion rate(UAER), urinary beta 2-microglobulin(beta 2-MG), urinary microalbumin(mA1 b), bone mineral density(L_2-L_4, femoral neck, Ward triangle, femoral trochanter, hip joint), serum calcium, phosphorus, 25-hydroxyvitamin D(25-OH-D_3), parathyroid hormone(PTH), bone gla protein(BGP), procollagen type I N propeptide(PINP) and C-terminal telopeptides of type I collagen(β-CTX) were compared between the two groups after treatment. Results After treatment, UAER, urinary beta 2-MG and 24-hour urinary albumin levels in the experimental group were lower than those in the control group(P<0.05). After treatment, the bone mineral density of each detection site in the experimental group was higher than that in the control group(P<0.05). The serum calcium of the experimental group were higher than those of the control group, and the serum phosphorus of the experimental group were lower than those of the control group(P<0.05). After treatment, the levels of 25-OH-D_3 and PINP in the experimental group were significantly higher than those in the control group(P<0.05), and PTH, BGP and beta-CTX in the experimental group were significantly lower than those in the control group(P<0.05). The total incidence of adverse reactions in the control group and the experimental group were 8.93% and 12.07%, respectively, with no significant difference(P=0.585). Conclusion In the treatment of type 2 diabetic nephropathy, vitamin D combined with Siglitatin can effectively reduce urinary protein, increase bone mineral density and improve bone metabolism in patients with better safety.
引文
[1] 王栋栋,魏彤,何素梅,等.西格列汀延缓或阻止2型糖尿病肾病进展的实验研究[J].中国临床药理学杂志,2016,32(1):45-47,54.
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[3] HOOKHAM M B,O’DONOVAN H C,CHURCH R H,et al.Insulin receptor substrate-2 is expressed in kidney epithelium and up-regulated in diabetic nephropathy[J].FEBS J,2013,280(14):3232-3243.
[4] GIELEN E,O’NEILL T,PYE S,et al.Bone turnover markers predict hip bone loss in elderly European men:results of the European Male Ageing Study (EMAS)[J].Osteoporos Int,2015,26(2):617-627.
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[7] 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2013年版)[J].中国糖尿病杂志,2014,22(8):2-42.
[8] ORCHARD T J,TEMPROSA M,BARRETT-CONNOR E,et al.Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors:a report from the DPP Outcomes Study[J].Diabet Med,2013,30(1):46-55.
[9] MEGA C,TEIXEIRA-DE-LEMOS E,FERNANDES R,et al.Renoprotective effects of the dipeptidyl peptidase-4 inhibitor sitagliptin:a review in type 2 diabetes[J].J Diabetes Res,2017,2017(8):5164292.
[10] KESHAVARZ K,LOTFI F,SANATI E,et al.Linagliptin versus sitagliptin in patients with type 2 diabetes mellitus:a network meta-analysis of randomized clinical trials[J].Daru,2017,25(1):23.
[11] 金洁娜,孙慧燕,徐赵钕,等.西格列汀对老年糖尿病肾病患者临床指标的影响[J].中国老年学杂志,2016,36(1):79-81.
[12] GON?ALVES A,MARQUES C,LEAL E,et al.Dipeptidyl peptidase-IV inhibition prevents blood-retinal barrier breakdown,inflammation and neuronal cell death in the retina of type 1 diabetic rats[J].Biochim Biophys Acta,2014,1842(9):1454-1463.
[13] ZHAO L,SUN T,WANG L.Chitosan oligosaccharide improves the therapeutic efficacy of sitagliptin for the therapy of Chinese elderly patients with type 2 diabetes mellitus[J].Ther Clin Risk Manag,2017,13(2):739-750.
[14] 王丹阳,苗润培,熊敏,等.西格列汀的作用机制和二肽基肽酶4抑制剂对肾脏作用的临床研究进展[J].中国医刊,2018,53(5):482-485.
[15] 任小军,刘高虹,薛福平,等.西格列汀对糖尿病肾病大鼠肾脏JNK信号通路的影响[J].中国药物与临床,2016,24(3):333-335.
[16] KONDO Y,HARADA N,HAMASAKI A,et al.Sitagliptin monotherapy has better effect on insulinogenic index than glimepiride monotherapy in Japanese patients with type 2 diabetes mellitus:a 52-week,multicenter,parallel-group randomized controlled trial[J].Diabetol Metab Syndr,2016,8(1):1-9.
[17] 郑涓,陈璐璐.DPP-4抑制剂对心血管系统的影响及在中国2型糖尿病患者中的应用进展[J].临床药物治疗杂志,2015,13(6):6-10.
[18] 呼双琴,白小岗,李霞,等.西格列汀对2型糖尿病患者微量白蛋白尿影响的研究[J].现代生物医学进展,2016,16(27):5324-5326,5352.
[19] 王菁楠,顾明君,赵泽飞,等.西格列汀对2型糖尿病肾损害患者尿微量白蛋白的影响[J].中国新药与临床杂志,2013,32(4):289-292.
[2] DEVARAJAN T V,VENKATARAMAN S,KANDASAMY N,et al.Comparative evaluation of safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus:Indian multicentric randomized trial-START study[J].Indian J Endocrinol Metab,2017,21(5):745-750.
[3] HOOKHAM M B,O’DONOVAN H C,CHURCH R H,et al.Insulin receptor substrate-2 is expressed in kidney epithelium and up-regulated in diabetic nephropathy[J].FEBS J,2013,280(14):3232-3243.
[4] GIELEN E,O’NEILL T,PYE S,et al.Bone turnover markers predict hip bone loss in elderly European men:results of the European Male Ageing Study (EMAS)[J].Osteoporos Int,2015,26(2):617-627.
[5] 孟艳秋,张宇,刘凤鑫,等.二肽基肽酶Ⅳ抑制剂的药理作用及其机制研究[J].现代药物与临床,2013,28(2):101-107.
[6] KAWASAKI I,HIURA Y,TAMAI A,et al.Sitagliptin reduces the urine albumin-to-creatinine ratio in type 2 diabetes through decreasing both blood pressure and estimated glomerular filtration rate[J].J Diabetes,2015,7(1):41-46.
[7] 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2013年版)[J].中国糖尿病杂志,2014,22(8):2-42.
[8] ORCHARD T J,TEMPROSA M,BARRETT-CONNOR E,et al.Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors:a report from the DPP Outcomes Study[J].Diabet Med,2013,30(1):46-55.
[9] MEGA C,TEIXEIRA-DE-LEMOS E,FERNANDES R,et al.Renoprotective effects of the dipeptidyl peptidase-4 inhibitor sitagliptin:a review in type 2 diabetes[J].J Diabetes Res,2017,2017(8):5164292.
[10] KESHAVARZ K,LOTFI F,SANATI E,et al.Linagliptin versus sitagliptin in patients with type 2 diabetes mellitus:a network meta-analysis of randomized clinical trials[J].Daru,2017,25(1):23.
[11] 金洁娜,孙慧燕,徐赵钕,等.西格列汀对老年糖尿病肾病患者临床指标的影响[J].中国老年学杂志,2016,36(1):79-81.
[12] GON?ALVES A,MARQUES C,LEAL E,et al.Dipeptidyl peptidase-IV inhibition prevents blood-retinal barrier breakdown,inflammation and neuronal cell death in the retina of type 1 diabetic rats[J].Biochim Biophys Acta,2014,1842(9):1454-1463.
[13] ZHAO L,SUN T,WANG L.Chitosan oligosaccharide improves the therapeutic efficacy of sitagliptin for the therapy of Chinese elderly patients with type 2 diabetes mellitus[J].Ther Clin Risk Manag,2017,13(2):739-750.
[14] 王丹阳,苗润培,熊敏,等.西格列汀的作用机制和二肽基肽酶4抑制剂对肾脏作用的临床研究进展[J].中国医刊,2018,53(5):482-485.
[15] 任小军,刘高虹,薛福平,等.西格列汀对糖尿病肾病大鼠肾脏JNK信号通路的影响[J].中国药物与临床,2016,24(3):333-335.
[16] KONDO Y,HARADA N,HAMASAKI A,et al.Sitagliptin monotherapy has better effect on insulinogenic index than glimepiride monotherapy in Japanese patients with type 2 diabetes mellitus:a 52-week,multicenter,parallel-group randomized controlled trial[J].Diabetol Metab Syndr,2016,8(1):1-9.
[17] 郑涓,陈璐璐.DPP-4抑制剂对心血管系统的影响及在中国2型糖尿病患者中的应用进展[J].临床药物治疗杂志,2015,13(6):6-10.
[18] 呼双琴,白小岗,李霞,等.西格列汀对2型糖尿病患者微量白蛋白尿影响的研究[J].现代生物医学进展,2016,16(27):5324-5326,5352.
[19] 王菁楠,顾明君,赵泽飞,等.西格列汀对2型糖尿病肾损害患者尿微量白蛋白的影响[J].中国新药与临床杂志,2013,32(4):289-292.