社区医院应用骨化三醇联合氯沙坦治疗糖尿病肾病的疗效研究
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摘要
目的观察口服补充维生素D类药物能否进一步降低糖尿病肾病患者尿蛋白,减缓肾功能的恶化,改善糖代谢。方法选取本社区2型糖尿病、Ⅲ-Ⅳ期糖尿病肾病(CKD 1-3期)患者84例,将患者按随机数字表法分为观察组和对照组,两组在常规治疗基础上,对照组给予氯沙坦100 mg/d,观察组给予骨化三醇0. 25μg/d+氯沙坦100 mg/d,干预12个月,比较两组治疗后6个月、12个月时的疗效。结果治疗12个月后,观察组与对照组相比,血磷下降(P=0. 019);与入组前比较,观察组舒张压、血清胱抑素C、血磷、尿微量清蛋白/尿肌酐下降(P=0. 041、P <0. 001、P=0. 007、P=0. 008),血清25(OH) D升高(P=0. 037);与入组前比较,对照组血清25-(OH) D升高(P <0. 001),血清胱抑素C下降(P <0. 001)。血清25-(OH) D与FIns呈正相关(r=0. 26,P <0. 001),与空腹血糖、糖化血红蛋白、三酰甘油、低密度脂蛋白胆固醇、血磷呈负相关(r=-0. 30、-0. 29、-0. 34、-0. 26、-0. 22,P <0. 001。结论小剂量骨化三醇联合氯沙坦能够升高血清25-(OH) D浓度、改善糖尿病肾病患者钙磷代谢,并对肾脏提供一定的保护。
Objective To study and observe whether oral vitamin D supplements can further reduce urine protein excretion of diabetic nephropathy patients,slow down the deterioration of renal function and improve sugar metabolism. Methods A total of 84 patients with type 2 diabetes and stage Ⅲ-Ⅳ diabetic nephropathy( CKD 1-3) were selected and divided into observation group and control group in random. On the basis of routine treatment,the control group were given losartan 100 mg/d,the observation group were given calcitriol 0. 25 μg/d + losartan 100 mg/d,and intervention was carried out for 12 months. The efficacy of the two groups at 6 months and 12 months after treatment were compared. Results After 12 months of treatment,blood phosphorus decreased in the observation group compared with the control group,( P = 0. 019). After the treatment,diastolic blood pressure,serum cystatin C,blood phosphorus,urine albumin/creatinine decreased( P = 0. 041,P < 0. 001,P = 0. 007,P = 0. 008),serum 25-hydroxyvitamin D increased( P = 0. 037) in the observation group. After the treatment,the serum 25-hydroxyvitamin D increased( P < 0. 001) and the serum cystatin C decreased( P < 0. 001) in the control group. Serum 25( OH) D was positively correlated with FIns( r = 0. 26,P < 0. 001),and negatively correlated with FPG,HbA_1c,TG,LDL-C,P( r =-0. 30,-0. 29,-0. 34,-0. 26,-0. 22,P < 0. 001). Conclusion Low dose calcitriol combined with losartan can increase serum 25-hydroxyvitamin D concentration,regulate calcium and phosphorus metabolism and provide some reno-protenction for patients with DKD.
Objective To study and observe whether oral vitamin D supplements can further reduce urine protein excretion of diabetic nephropathy patients,slow down the deterioration of renal function and improve sugar metabolism. Methods A total of 84 patients with type 2 diabetes and stage Ⅲ-Ⅳ diabetic nephropathy( CKD 1-3) were selected and divided into observation group and control group in random. On the basis of routine treatment,the control group were given losartan 100 mg/d,the observation group were given calcitriol 0. 25 μg/d + losartan 100 mg/d,and intervention was carried out for 12 months. The efficacy of the two groups at 6 months and 12 months after treatment were compared. Results After 12 months of treatment,blood phosphorus decreased in the observation group compared with the control group,( P = 0. 019). After the treatment,diastolic blood pressure,serum cystatin C,blood phosphorus,urine albumin/creatinine decreased( P = 0. 041,P < 0. 001,P = 0. 007,P = 0. 008),serum 25-hydroxyvitamin D increased( P = 0. 037) in the observation group. After the treatment,the serum 25-hydroxyvitamin D increased( P < 0. 001) and the serum cystatin C decreased( P < 0. 001) in the control group. Serum 25( OH) D was positively correlated with FIns( r = 0. 26,P < 0. 001),and negatively correlated with FPG,HbA_1c,TG,LDL-C,P( r =-0. 30,-0. 29,-0. 34,-0. 26,-0. 22,P < 0. 001). Conclusion Low dose calcitriol combined with losartan can increase serum 25-hydroxyvitamin D concentration,regulate calcium and phosphorus metabolism and provide some reno-protenction for patients with DKD.
引文
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[3] CARDOSO-SáNCHEZ L I,COMEZ-DFAZ R A,WACHER N H. Vitamin D intake associates with insulin resistance in type 2diabetes,but not in latent autoimmune diabrtes in adults[J]. Nutr Res,2015,35(8):689-699.
[4] PRIETL B,TREIBER G,MADER J K,et al. High-dose cholecaciferol supplementation significantly increases peripheral CD4+Tregs in healthy Adults without negatively affecting the frequency of other immune cells[J]. Eur J Nutr,2014,53(3):751-759.
[5] LU H K,ZHANG Z,KE Y H,et al. High prevalence of vitamin D insufficiency in China:relationship with the level of parathyriod hormone and makers of bone turnover[J].Plos One,2012,7(11):e47264[2018-08-17]. https://www. ncbi. nlm. nih. gov/pubmed/23144810. DOI:10.1371/journal. pone. 0047264.
[6] HIRANI V,CUMMING R G,LE COUTEUR D G,et al.Low levels of 25-hydroxy vitamin D and active 1,25-dihydroxynitamin D independently associated with type 2 diabetes mellitus in older Australian men:the concord health and ageing in men project[J]. J Am Geriatr Soc,2014,62(9):1741-1747.
[7] DIAZ V A,MAINOUS AG 3RD,CAREK P J,et al. Theassociation of vita-minD deficiency and insufficiency with diabetic nephropathy:im-plications for health disparities[J]. J Am Board Fam Med,2009,22(5):521-527.
[8] ZIMPELMANN J,KUMAR D,LEVINE D Z,et al. Early diabetes mellitus stimulates proximal tubulerenin mRNA expression intherat[J]. Kidney Int,2000,58(6):2320-2330.
[9] ZHANG Z,YUAN W,SUN L,et al. 1,25-Dihydroxy vitamin D3 targe-ting of NF-kappa B suppresses high glucoseinduced MCP-1 expression in mesangial cells[J]. KidneyInt,2007,72(2):193-201.
[10] THOMAS M C,COOPER M E. Into the light diabetic nephrathy and vitamin D[J]. Lancet,2010,376(9752):1521-1522.
[11] GAL-MOSCOVICI A,SPRAGUE S M. Use of vitamin D in chronic kidney disease patients[J]. Kidney Int,2010,78(2):146-151.
[12] LIM L L,NG Y M,KANG P S,et al. Association between serum 25-hydroxyvitamin D and glycated hemoglobin levels in type 2 diabetes patients with chronic kidney disease[J]. J Diabetes Investig,2018,9(2):375-382.
[13]李文静,秦爱平,陈凯,等.骨化三醇辅治老年2型糖尿病患者的疗效及其对血清炎性因子的影响[J].疑难病杂志,2017,16(7):682-685.
[2] FERNáNDEZ-JUáREZ G,LU?O J,BARRIO V,et al. 25(OH)vitamin D levels and renal disease progression in patients with type 2 diabetic nephropathy and blockade of the renin-angiotensin system[J]. Clin J Am Soc Nephrol,2013,22(8):1870-1876.
[3] CARDOSO-SáNCHEZ L I,COMEZ-DFAZ R A,WACHER N H. Vitamin D intake associates with insulin resistance in type 2diabetes,but not in latent autoimmune diabrtes in adults[J]. Nutr Res,2015,35(8):689-699.
[4] PRIETL B,TREIBER G,MADER J K,et al. High-dose cholecaciferol supplementation significantly increases peripheral CD4+Tregs in healthy Adults without negatively affecting the frequency of other immune cells[J]. Eur J Nutr,2014,53(3):751-759.
[5] LU H K,ZHANG Z,KE Y H,et al. High prevalence of vitamin D insufficiency in China:relationship with the level of parathyriod hormone and makers of bone turnover[J].Plos One,2012,7(11):e47264[2018-08-17]. https://www. ncbi. nlm. nih. gov/pubmed/23144810. DOI:10.1371/journal. pone. 0047264.
[6] HIRANI V,CUMMING R G,LE COUTEUR D G,et al.Low levels of 25-hydroxy vitamin D and active 1,25-dihydroxynitamin D independently associated with type 2 diabetes mellitus in older Australian men:the concord health and ageing in men project[J]. J Am Geriatr Soc,2014,62(9):1741-1747.
[7] DIAZ V A,MAINOUS AG 3RD,CAREK P J,et al. Theassociation of vita-minD deficiency and insufficiency with diabetic nephropathy:im-plications for health disparities[J]. J Am Board Fam Med,2009,22(5):521-527.
[8] ZIMPELMANN J,KUMAR D,LEVINE D Z,et al. Early diabetes mellitus stimulates proximal tubulerenin mRNA expression intherat[J]. Kidney Int,2000,58(6):2320-2330.
[9] ZHANG Z,YUAN W,SUN L,et al. 1,25-Dihydroxy vitamin D3 targe-ting of NF-kappa B suppresses high glucoseinduced MCP-1 expression in mesangial cells[J]. KidneyInt,2007,72(2):193-201.
[10] THOMAS M C,COOPER M E. Into the light diabetic nephrathy and vitamin D[J]. Lancet,2010,376(9752):1521-1522.
[11] GAL-MOSCOVICI A,SPRAGUE S M. Use of vitamin D in chronic kidney disease patients[J]. Kidney Int,2010,78(2):146-151.
[12] LIM L L,NG Y M,KANG P S,et al. Association between serum 25-hydroxyvitamin D and glycated hemoglobin levels in type 2 diabetes patients with chronic kidney disease[J]. J Diabetes Investig,2018,9(2):375-382.
[13]李文静,秦爱平,陈凯,等.骨化三醇辅治老年2型糖尿病患者的疗效及其对血清炎性因子的影响[J].疑难病杂志,2017,16(7):682-685.