维生素D与糖尿病肾病的研究进展
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摘要
糖尿病肾病是糖尿病常见的并发症之一,流行病学研究显示维生素D缺乏与糖尿病肾病的发生有关,维生素D可能是影响糖尿病肾病的重要因素。目前,维生素D缺乏与糖尿病肾病发病的关系及补充维生素D改善糖尿病肾病患者的状态成为研究的热点。此文总结近年国内外的相关研究,系统全面地从维生素D与糖尿病肾病关系、维生素D对糖尿病肾病保护作用机制以及维生素D在糖尿病肾病患者中的应用等方面介绍维生素D与糖尿病肾病之间关系的研究进展,重点介绍维生素D与糖尿病肾病相互关系的生理学机制,并从维生素D受体信号通路及基因多态性方面解释人群实验中补充维生素D对糖尿病肾病防治效果差异性产生的原因。未来,随着维生素D在糖尿病肾病发病机制中作用的进一步揭示,将为糖尿病肾病患者的治疗及并发症的预防提供更好的指导。
Diabetic nephropathy is one of the common complications of diabetes.Epidemiological studies have shown that vitamin D deficiency is associated with the development of diabetic nephropathy.Therefore,Vitamin D may be an important factor affecting diabetic nephropathy.At present,the relationship between vitamin D and the pathogenesis of diabetic nephropathy and vitamin D supplementation improve the status of patients with diabetic nephropathy have become a research hotspot.This article summarized relevant research at home and abroad in recent years,and the system comprehensively introduced the research progress between vitamin D and diabetic nephropathy from these aspects which included relationship between vitamin D and diabetic nephropathy,protective mechanism of vitamin D on diabetic nephropathy and application of vitamin D in patients with diabetic nephropathy.The physiological mechanism of the relationship between vitamin D and diabetic nephropathy was introduced,and the causes of the difference in the prevention and treatment of diabetic nephropathy in the population experiment were explained from the aspects of vitamin D receptor signaling pathway and gene polymorphism.In the future,with the further revealing role of vitamin D in the pathogenesis of diabetic nephropathy,it will provide better guidance for the treatment of patients with diabetic nephropathy and the prevention of complications.
Diabetic nephropathy is one of the common complications of diabetes.Epidemiological studies have shown that vitamin D deficiency is associated with the development of diabetic nephropathy.Therefore,Vitamin D may be an important factor affecting diabetic nephropathy.At present,the relationship between vitamin D and the pathogenesis of diabetic nephropathy and vitamin D supplementation improve the status of patients with diabetic nephropathy have become a research hotspot.This article summarized relevant research at home and abroad in recent years,and the system comprehensively introduced the research progress between vitamin D and diabetic nephropathy from these aspects which included relationship between vitamin D and diabetic nephropathy,protective mechanism of vitamin D on diabetic nephropathy and application of vitamin D in patients with diabetic nephropathy.The physiological mechanism of the relationship between vitamin D and diabetic nephropathy was introduced,and the causes of the difference in the prevention and treatment of diabetic nephropathy in the population experiment were explained from the aspects of vitamin D receptor signaling pathway and gene polymorphism.In the future,with the further revealing role of vitamin D in the pathogenesis of diabetic nephropathy,it will provide better guidance for the treatment of patients with diabetic nephropathy and the prevention of complications.
引文
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[19] Melamed ML,Astor B,Michos ED,et al.25-hydroxyvitamin D levels,race,and the progression of kidney disease [J].J AmSoc Nephrol,2009,20(12):2631-2639.
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[23] Zhou C,Lu F,Cao K,et al.Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice [J].Kidney Int,2008,74(2):170-179.
[24] Ohara I,Tanimoto M,Gohda T,et al.Effect of combination therapy with angiotensin receptor blocker and 1,25-dihydroxyvitamin D3 in type 2 diabetic nephropathy in KK-A(y)/Ta mice [J].Nephron Exp Nephrol,2011,117(4):124-132
[25] Li YC,Kong J,Wei M,et al.1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system [J].J Clin Invest,2002,110(2):229-238.
[26] Aljabri KS,Bokhari SA,Khan MJ.Glycemic changes after vitaimin D supplementation with type 1 diabetes mellitus and vitamin D deficiency [J].Ann Saudi Med,2010,30(6):454-458.
[27] Kayaniyil S,Vieth R,Prioletta A,et al.Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes[J].Diabetes Care,2010,33(6):1379-1381.
[28] Awad AB,Alappat L,Valerio M.Vitamin D and metabolic syndrome risk factors:evidence and mechanisms[J].Crit Rev Food Sci Nutr,2012,52(2):103-112.
[29] Mao L,Ji F,Liu Y,et al.Calcitriol plays a protective role in diabetic nephropathy through anti-inflammatory effects [J].Int J Clin Exp Med,2014,7(12):5437-5444.
[30] Nakai K,Fujii H,Kono K,et al.Vitamin D activates the Nrf2-Keap1 antioxidant pathway and ameliorates nephropathy in diabetic rats [J].American Journal of Hypertension,2014,27(4):586-595.
[31] Tanaka M,Tokunaga K,Komaba H,et al.Vitamin D receptor activator reduces oxidative stress in hemodialysis patients with secondary hyperparathyroidism [J].Ter Apher Dial,2011,15(2):161-168.
[32] Husain K,Ferder L,Mizobuchi M,et al.Combination therapy with paricalcitol and enalapril ameliorates cardiac oxidative injury in uremic rats[J].Am J Nephrol,2009(29):465-472.
[33] Wang Y,Deb DK,Zhang Z,et al.Vitamin D receptor signaling in podocytes protects against diabetic nephropathy [J].J Am Soc Nephrol,2012,23(12):1977.
[34] Zhang Z,Sun L,Wang Y,et al.Renoprotective role of the vitamin D receptor in diabetic nephropathy [J].Kidney Int,2008,73 (2):163-171.
[35] Uitterlinden AG,Fang Y,Van Meurs JB,et al.Genetics and biology of vitamin D receptor polymorphisms [J].Gene,2004,338(2):143-156.
[36] Palomer X,González -Clemente JM,Blanco -Vaca F,et al.Role of vitamin D in the pathogenesis of type 2 diabetes mellitus [J].Diatetes Obes Metab,2008,10(3):185-197.
[37] Vedralová MI,Kotrbova-Kozak A,Zelezníková V,et al.Polymorphisms in the vitamin D receptor gene and parathyroid hormone gene in the development and progression of diabetes mellitus and its chronic complications,diabetic nephropathy and non-diabetic renal disease[J].Kidney Blood Press Res,2012,36(1):1-9.
[38] Rostand SG,Warnock DG.Introduction to vitamin D symposium [J].Clin J Am Soc Nephrol,2008(3):1534.
[2] Bordon,Y.Asthma and allergy:vitamin D3 primes neonatal immune system [J].Nat Rev Immunol,2017,17(8):467.
[3] Berridge,MJ.Vitamin D3 and depression:cellular and regulatory mechanisms [J].Pharmacol Rev,2017,69(2):80-92.
[4] Wang TJ.Vitamin D and cardiovascular disease [J].Annu Rev Med,2016,67(8):261-272.
[5] Rolf L,Muris AH,Bol Y,et al.Vitamin D3 supplementation in multiple sclerosis:symptoms and biomarkers of depression [J].J Neurol Sci,2017,378(1):30-35.
[6] Vaidya A,Williams JS.The relationship between vitamin D and the reninangiotensin system in the pathophysiology of hypertension,kidney disease,and diabetes [J].Metabolism,2012,61(4):450-458.
[7] Vaidya A,Forman JP.Vitamin D and vascular disease:the current and future status of vitamin D therapy in hypertension and kidney disease [J].Curr Hypertens Rep,2012,14(2):111-119.
[8] Wimalawansa,SJ.Vitamin D3 and cardiovascular diseases:causality [J].J Steroid Biochem Mol Biol,2018,175(1):29-43.
[9] Vaidya A,Sun B,Larson C,et al.Vitamin D3 therapy corrects the ti-ssue sensitivity to angiotensin ii akin to the action of a converting enzyme inhibitor in obese hypertensives:an interventional study [J].J Clin Endocrinol Metab,2012,97(7):2456-2465.
[10] Guariguata L,Whiting DR,Hambleton I,et al.Global estimates of diabetes prevalence for 2013 and projections for 2035 [J].Diabetes Res Clin Pract,2014,103(2):137-149.
[11] Angellotti E,D’Alessio D,Dawson-Hughes B,et al.Vitamin D supplementation in patients with type 2 diabetes:the vitamin D for established type 2 diabetes (DDM2) Study [J].J Endocr Soc,2018,2(4):310-321.
[12] Zhao J,Xia W,Nie M,et al.The levels of bone turnover markers in Chinese postmenopausal women:peking vertebral fracture study [J].Menopause,2011,18(11):1237-1243.
[13] Yan P,Li LJ.Serum 25-hydroxyvitamin D level and diabetic nephropathy in patients with type 2 diabetes mellitus [J].Int Urol Nephrol,2015,47(6):983-989
[14] Shroff,R.,Wan M,Nagler EV,et al.Clinical practice recommendations for treatment with active vitamin D3 analogues in children with chronic kidney disease stages 2-5 and on dialysis [J].Nephrol Dial Transplant,2017,32(7):1114-1127.
[15] Alam U,Najam O,Al-Himdani S,et al.Marked vitamin D deficiency in patients with diabetes in the UK:ethnic and seasonal diffe-rences and an association with dyslipidaemia [J].Diabet Med,2012,29(10):1343-1345.
[16] Rahmadhani R,Zaharan NL,Mohamed Z,et al.The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency,obesity and insulin resistance in adolescents residing in a tropical country [J].PLoS One,2017,12(6):e 0178695.
[17] Mehrotra R,Kermah DA,Salusky IB,et al.Chronic kidney disease,hypovitaminosis D,and mortality in the United States [J].Kidney Int,2009,76(9):977-983.
[18] De Zeeuw D,Agarwal R,Amdahl M,et al.Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study):a randomised controlled trial [J].Lancet,2007,376(9752):1543-1551.
[19] Melamed ML,Astor B,Michos ED,et al.25-hydroxyvitamin D levels,race,and the progression of kidney disease [J].J AmSoc Nephrol,2009,20(12):2631-2639.
[20] Wang AY,Lam CW,Sanderson JE,et al.Serum 25-hydroxyvitamin D status and cardiovascular outcomes inchronic peritoneal dialysis patients:a 3-y prospective cohort study [J].Am J Clin Nutr,2008,87(6):1631-1638.
[21] Damasiewicz MJ,Magliano DJ,Daly RM,et al.Serum 25-hydroxyvitamin D deficiency and the 5-year incidence of CKD [J].Am J Kidney Dis,2013,62(1):58-66.
[22] Bader M.Tissue renin-angiotensin-aldosterone systems:targets for pharmacological therapy [J].Annu Rev Pharmacol Toxicol,2010,50(10):439-465.
[23] Zhou C,Lu F,Cao K,et al.Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice [J].Kidney Int,2008,74(2):170-179.
[24] Ohara I,Tanimoto M,Gohda T,et al.Effect of combination therapy with angiotensin receptor blocker and 1,25-dihydroxyvitamin D3 in type 2 diabetic nephropathy in KK-A(y)/Ta mice [J].Nephron Exp Nephrol,2011,117(4):124-132
[25] Li YC,Kong J,Wei M,et al.1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system [J].J Clin Invest,2002,110(2):229-238.
[26] Aljabri KS,Bokhari SA,Khan MJ.Glycemic changes after vitaimin D supplementation with type 1 diabetes mellitus and vitamin D deficiency [J].Ann Saudi Med,2010,30(6):454-458.
[27] Kayaniyil S,Vieth R,Prioletta A,et al.Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes[J].Diabetes Care,2010,33(6):1379-1381.
[28] Awad AB,Alappat L,Valerio M.Vitamin D and metabolic syndrome risk factors:evidence and mechanisms[J].Crit Rev Food Sci Nutr,2012,52(2):103-112.
[29] Mao L,Ji F,Liu Y,et al.Calcitriol plays a protective role in diabetic nephropathy through anti-inflammatory effects [J].Int J Clin Exp Med,2014,7(12):5437-5444.
[30] Nakai K,Fujii H,Kono K,et al.Vitamin D activates the Nrf2-Keap1 antioxidant pathway and ameliorates nephropathy in diabetic rats [J].American Journal of Hypertension,2014,27(4):586-595.
[31] Tanaka M,Tokunaga K,Komaba H,et al.Vitamin D receptor activator reduces oxidative stress in hemodialysis patients with secondary hyperparathyroidism [J].Ter Apher Dial,2011,15(2):161-168.
[32] Husain K,Ferder L,Mizobuchi M,et al.Combination therapy with paricalcitol and enalapril ameliorates cardiac oxidative injury in uremic rats[J].Am J Nephrol,2009(29):465-472.
[33] Wang Y,Deb DK,Zhang Z,et al.Vitamin D receptor signaling in podocytes protects against diabetic nephropathy [J].J Am Soc Nephrol,2012,23(12):1977.
[34] Zhang Z,Sun L,Wang Y,et al.Renoprotective role of the vitamin D receptor in diabetic nephropathy [J].Kidney Int,2008,73 (2):163-171.
[35] Uitterlinden AG,Fang Y,Van Meurs JB,et al.Genetics and biology of vitamin D receptor polymorphisms [J].Gene,2004,338(2):143-156.
[36] Palomer X,González -Clemente JM,Blanco -Vaca F,et al.Role of vitamin D in the pathogenesis of type 2 diabetes mellitus [J].Diatetes Obes Metab,2008,10(3):185-197.
[37] Vedralová MI,Kotrbova-Kozak A,Zelezníková V,et al.Polymorphisms in the vitamin D receptor gene and parathyroid hormone gene in the development and progression of diabetes mellitus and its chronic complications,diabetic nephropathy and non-diabetic renal disease[J].Kidney Blood Press Res,2012,36(1):1-9.
[38] Rostand SG,Warnock DG.Introduction to vitamin D symposium [J].Clin J Am Soc Nephrol,2008(3):1534.