吡格列酮对2型糖尿病患者血脂及其并发症的影响
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摘要
目的:研究盐酸吡格列酮(PIG)对2型糖尿病患者血脂、血清超敏C-反应蛋(hs-CRP)、尿白蛋白排泄率、骨密度的影响。方法:选取于2009年3月至2010年1月在我院就诊血糖控制不佳的2型糖尿病患者50例,给予口服PIG治疗12周;检测患者治疗前后的身高、体重、血压、空腹血糖(FPG)、空腹胰岛素(FINS)、血脂谱、hs-CRP、尿白蛋白排泄率(UAER)、骨密度(BMD);计算体重指数(BMI)、胰岛素抵抗指数(HOMA-IR)。对测量数据行t检验或者秩和检验进行分析。结果:1.PIG治疗后FPG、FINS、HOMA-IR、甘油三酯、hs- CRP、UAER较治疗前下降(P<0.05);2.高密度脂蛋白胆固醇较前升高(P <0.05);3.其余BMI、血压、总胆固醇、低密度脂蛋白、脂蛋白(a)、骨密度无显著变化。结论:应用PIG在改善胰岛素抵抗、降低血糖的同时可调节血脂、降低hs-CRP、减少尿微量白蛋白,从而延缓糖尿病及糖尿病肾病的发生和发展。短期内使用PIG对骨密度无明显影响。
Objective: To observe the effects of pioglitazone (PIG) on blood lipids , high sensitive C-reactive protein (hs-CRP), urine albumin excretory rate (UAER) ,and bone mineral density (BMD) in patients with type 2 diabetes mellitus(T2DM). Methods: Fifty T2DM patients with poorly controlled blood glucose were given PIG for 12 weeks in our hospital between March 2009 and January 2010; The changes of of body height, body weight, blo- od pressure, fasting blood glucose (FPG), fasting insulin (FINS), blood lipids, hs-CRP , UAER , and BMD were measured in patients at the baseline and 12weeks after the therapy. Homeostasis model assessment indexes (HOMA-IR) was calculated by the HOMA model. Body mass index (BMI) was also calculated. For all data, t test or Rank sum test were con- duct. Results:1.There was a significant decrease in FPG,FINS,HOMA-IR, triglyceride (T G), hs-CRP and UAER (P < 0.05) after PIG treatment for 12 weeks; 2. The high-density lioprotein-cholesterol (HDL-C) level increased compared to the baseline (P <0.05). 3. However ,there was no signficant difference in BMI, blood pressure, totalcholesterol (TC) , low-density lioprotein-cholesterol (LDL-C), Lp(a),BMD(P >0.05). Conclusion: The treatment of PIG can not only improve insulin sensitivity but also decrease the level of hs-CRP and UREA. PIG can prevent the development of diabetes melleius and diabetic nephropathy. PIG has no impact on BMD during the treatment in short time.
Objective: To observe the effects of pioglitazone (PIG) on blood lipids , high sensitive C-reactive protein (hs-CRP), urine albumin excretory rate (UAER) ,and bone mineral density (BMD) in patients with type 2 diabetes mellitus(T2DM). Methods: Fifty T2DM patients with poorly controlled blood glucose were given PIG for 12 weeks in our hospital between March 2009 and January 2010; The changes of of body height, body weight, blo- od pressure, fasting blood glucose (FPG), fasting insulin (FINS), blood lipids, hs-CRP , UAER , and BMD were measured in patients at the baseline and 12weeks after the therapy. Homeostasis model assessment indexes (HOMA-IR) was calculated by the HOMA model. Body mass index (BMI) was also calculated. For all data, t test or Rank sum test were con- duct. Results:1.There was a significant decrease in FPG,FINS,HOMA-IR, triglyceride (T G), hs-CRP and UAER (P < 0.05) after PIG treatment for 12 weeks; 2. The high-density lioprotein-cholesterol (HDL-C) level increased compared to the baseline (P <0.05). 3. However ,there was no signficant difference in BMI, blood pressure, totalcholesterol (TC) , low-density lioprotein-cholesterol (LDL-C), Lp(a),BMD(P >0.05). Conclusion: The treatment of PIG can not only improve insulin sensitivity but also decrease the level of hs-CRP and UREA. PIG can prevent the development of diabetes melleius and diabetic nephropathy. PIG has no impact on BMD during the treatment in short time.
引文
[1] Zeender E,Maedler K,Bosco D,et al. Pioglitazone and sodium salicylate protecthuman beta-cells against apop tosis and impaired function induced by glucose and interleukin-1 beta[J].J Clin EndocrinolMetab, 2004, 89 (10): 5059-5066.
[2] Walter H,Lubben G. Potential role of oral thiazolidinedione therapy in preserving beta-cell function in type 2 diabetes mellitus [J].J Drugs,2005, 65 (1):1-13
[3] Barzilay J I , Abraham L,Heckbert S R, et al. The relation of markers of infla- mmation to the development of glucose disorders in the elderly: the Cardiovasc- ular Healt h Study [J].Diabetes,2001,50 (10) :2384-2389.
[4] Tsuruda T, Kato J, Sumi T, et al .Combined use of brain natriuretic peptide and C-reactive protein for predicting cardiovascular risk in outpatients with type 2 diabetes mellitus[J].Vasc Healt h Risk Manag , 2007,3 (4) :417-423.
[5] Bloomgarden Z T. Inflammation and insulin resistance [J].Diabetes Care, 2003, 26 (5):1619-1623.
[6]李秀钧,邬云红.糖尿病是一种炎症性疾病[J].中华内分泌代谢疾病杂志,2003, 19 (4):251-253.
[7] Pradhan AD, Manson J E, Rifai N, et al. C-reactive protein ,interleukin 6 and risk of developing type 2 diabetes mellitus [J].JAMA ,2001 ,286 (3) :327-334.
[8]吴伟华,张巾超,于江波,等. 2型糖尿病及合并大血管病变糖尿病患者C反应蛋白水平观察[J].中华内分泌代谢杂志,2003 ,19 (4):257-259.
[9]朱麒钱,尤巧英,李成江,等.C反应蛋白与2型糖尿病大血管病变危险因素的相关性研究[J] .中华内分泌代谢杂志,2005 ,21 (4):320-321.
[10] Koschinsky ML. Lipoprotein (a) and at herosclerosis: new perspectives on the me- chanism of action of an enigmatic lipoprotein [J].Curr At heroscler Rep, 2005, 7 (5):389-395.
[11] Lima LM, Carvalho MG, Loures-Vale AA, et al. Increased serum levels of lipo- protein (a) correlated wit h t he severity of coronary artery disease in patients submitted to angiography [J].Arq Bras Cardiol, 2006, 87(3):260-266.
[12] Cerrato P ,Lmperiale D, Fomengo P, et al .Higher lipoprotein(a) levels in at herot hrombotic than lacunar ischemic cerebrovascular disease [J].Neurology, 2002, 58(4):653-655.
[13] Tseng CH. Lipoprotein (a) is an independent risk factor forperipheral arterial disease in Chinese type 2 diabetic patients in Taiwan [J].Diabetes Care, 2004, 27 (2):517-521.
[14] Dieplinger B, Lingenhel A, Baumgartner N, et al . Increased serum lipoprotein (a) concent rations and low molecular weight phenotypes of apolipoprotein (a) are associated with symptomatic peripheral arterial disease [J].Clin Chem, 2007, 53 (7):1298-1305.
[15] Hunninghake DB, McGovern ME, Koren M. A dose–ranging study of a new,once-daily, dual-component drug product containing niacin extended release and lovastatin [J].Clin Cardiol,2003,26(3):112-118.
[16] Florkowski CM. Management of co-existing diabetes mellitus and dyslipidemia: defining the role of thiazo-lidinediones [J].Am J Cardiovasc Drugs, 2002,2(1):15 - 21.
[17] Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists [J].Diabetes,2005,54 (8):2460- 2470.
[18] Van Wijk JP, de Koning EJ, Martens EP, et al. Thiazolidinediones and blood lipids in type 2 diabetes [J].Arterioscler Thromb Vasc Biol,2003,23 (10):1744 - 1749.
[19] Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dysl- ipidemia [J].Diabetes Care,2005,28(7):1547-1554
[20] Khanderia U,Pop-Busui R, Eagle KA. Thiazolidinediones in type 2 diabetes: a cardiology perspective (October) [J].Ann Pharmacother,2008,42(10):1466-1474
[21] Kim HJ, Kim SK, ShimWS, Rosiglitazone improves insulin sensitivity with ince- ased serum leptin levels in patients with type 2 diabetes mellitus [J].Diabetes Res Clin Pract,2008,81(1):42-49.
[22] Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetesmellitus:peroxisomalp roliferator-activated receptor agonists provide a rational therapeutic approach [J].J Clin Endo-crinol Metab, 2004, (2):463-478.
[23] Barzilay JI, Abraham L, Heckbert SR, et al. The relation of markers of inflamm- ation to the development of glucose disorders in the elderly: the Cardiovascular Health Study [J].Diabetes, 2001, 50(10):2384- 2389.
[24] Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis.Circulation [J]. 2002,105(7):1135- 1143
[25] Hong G, Davis B, Khatoon N, et al. PPARgamma- dependent anti -inflammatory action of rosiglitazone in human monocytes: suppressionof TNF alpha secretion is not mediated by PTEN regulation [J].Biochem Biophys Res Commun,2003,303 (3):782- 787
[26] Martin DU, Pan RC, Despont JP. High-sensitivity C- reactive protein:a new risk factor of diabetes mellitus [J]. Rev Med Suisse Romande, 2004,122(3):163- 166.
[27] Spranger J, Kroke A, MohligM, et a1. Inflammatory cytokines and the risk to de- velop type 2 diabetes: results of the prospective population- based European Pro- spective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study [J].Diabetes, 2003,52 (3):812.
[28] Pickup JC, Mattock MB, Chusney GD, et a1. NIDDM as a disease of the innate immune system: association of acute– phase reactants and interleukin-6 with metabolic syndrome X [J].Diabetologia, 1997,40(11):1286-1230.
[29] Pradhan AD, Manson JE, Rifai N, et a1. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus [J].JAMA,2001, 22(3)286-327.
[30] Pistrosch F, HerbingK,Kindel B,et al . Rosiglitazone improves glomerular hyperf- iltration, renal endothelial dysfunction, andmicroalbuminura of incipient diabetic nephropathy in patients [J].Diabetes,2005,54(7):2206-2211.
[31] Katavetin P ,Eiam-Ong S ,Suwanwalaikorn S. Pioglitazone reduces urinary protein and urinary transforming growth factor- beta excretion in patients with type 2 diabetes and overt nephropathy [J].J Med Assoc Thai ,2006,89(2):170-177.
[32] Bakris GL ,Ruilope LM,McMorn SO, et al .Rosiglitazone reduces microalbumin uria and blood pressure independently of glycemia in type 2 diabetes patients with microalbuminuria [J].J Hypertens,2006,24(10):2047-2055.
[33] Leideig Bruckner G,ziegler R. Diabetes mellitus a risk for osteoporosis[J]. Exp clin Endocrinol Diabetes 2001; 109 (supplz):S493 -514.
[34]郭燕,黄兆民,孟俊非,等.非胰岛素依赖型糖尿病患者骨密度变化的探讨[J].中华放谢学杂志.1999 ,33 (10) :705-707.
[35] Goldstein BJ. Cliniacal translation of“a diabetes outcome progression trail”: ADOPT appropriate combination oral therapies in type 2 diabetes [J].J Clin Endocrinol Metab,2007,92 (4):1226-1228.
[36] Schwartz AV, Seumeyer DE, Vittinqhoff E, et al. Thiazolidinedione (TZDs) use and bone loss in older diabetic adults[J].J Clin EndocrinolMetab,2006,91(9): 3349-3354.
[37] Oxana PL, Sylwia OR,William RH, et al. Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone [J].Endocrinology,2007,148 (6): 2669- 2680.
[38]李红兵,杨金奎,李毅斌,等,罗格列酮钠对非增生性糖尿病视网膜病变的作用[J].首都医科大学学报,2009,30(4):460-462.
[39] Dormandy JA, CharbonnelB, Eckland DJ, et al. Secondary prevention of macro vascular events in patientswith type 2 diabetes in the PROactive Study (PRO spective pioglitAzone Clinical Trial In macroVascular Events): a randomized controlled trial [J].Lancet,2005,366:1279-1289.
[40]李光伟,王金平,李春梅,等.胰岛素增敏剂罗格列酮抗高血压作用探讨[J].中华内科杂志, 2004, 43: 907-910.
[41] Schernthaner G, MatthewsDR, Charbonnel B, et al. Efficacy and safety of pioglit- azone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial [J].J Clin Endocrinol Metab,2004,89(12):6068-6076.
[42] Tan M, Johns D, González Gálvez G, et al. Effects of pioglitazone and glimepiride on glycemic control and insulin sensitivity in Mexican patients with type 2 diabetesmellitus: A multicenter, randomized, double-blind, parallel-group trial [J]. Clin Ther,2004,26 (5): 680-693.
[43] Raskin P, McGill J, SaadMF, et al. Combination therapy for type 2 diabetes:rep- aglinide plus rosiglitazone [J].Diabet Med,2004,21(4):329-335.
[44] Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Asso- ciation andAmerican Diabetes Association [J].Diabetes Care,2004,27 (1):256-263.
[45] Rosenstock J, Einhorn D, Hershon K, et al. Efficacy and safety of pioglitazone in type 2 diabetes: a randomised, placebo-controlled study in patients receiving stable insulin therapy [J].Int J Clin Pract,2002,56 (4):251-257.
[46] Berlie HD, Kalus JS, Jaber LA. Thiazolidinediones and the risk of edema: a meta analysis [J].Diabetes Res Clin Pract,2007,76(2):279-289.
[47]文迪雅Ⅳ期临床研究协作组,罗格列酮治疗2型糖尿病的临床观察[J].中华内科杂志,2003 ,42 (9) :636-638.
[48] Hussein Z,Wentworth JM,Nankervis AJ , et al. Effectiveness and side effects of thiazolidinediones for type 2 diabetes : real-life experience from a tertiary hospital [J] .Med J Aust,2004,181(10) :536-539
[49] Fonsece V,Effect of thiazolidinediones on body weight in patients with diabetes mellitus [J].AmJ Med,2003,115(8):42～48.
[1] Sato K,Sugawara A,Kudo M,et al.Expression of peroxisome proliferator activated receptor isoform proteins in the rat kidney. Hypertens Res, 2004, 27(6):417-425.
[2] Turtle KR.Linking metabolism and immunology:diabetic nephropathy is an inflammatory disease.J Am Soc Nephrol,2005,16:1537-1538
[3] Lee S, Kim W, Kang KP, et al. Agonist of peroxisome proliferators-activated rece- ptor gamma, rosiglitazone, reduces renal injury and dysfunction in a murine sep- sis model. Nephrol Dial Transplant, 2005, 20 (6): 1057-1065
[4] Agarwal R Anti-inflammatory effects of shortterm pioglitazone therapy in men with advanced diabetic nephropathy. Am J Physiol Renal Physiol, 2006, 290(3): F600- F605.
[5] Haraguchi K, Shimura H, Onaya T. Suppression of experimental crescentic glome- rulo nephritis by peroxisome proliferator-activated receptor gamma activators.Clin Exp Nephrol, 2003,7(1):27-32.
[6] BenigniA, Zoja C, Tomasoni S, et al. Transcrip tional regulation of nephrin gene by peroxisome proliferator-activated receptor-gamma agonist: molecularmechanism of the antiproteinuric effect of pioglitazone. J Am Soc Nephrol, 2006, 17 (6):1624- 1632.
[7] Sivarajah A, Chatterjee PK, PatelNS, et al. Agonists of peroxisome proliferator activated receptor-gamma reduce renal ischemia / reperfusion injury.Am J Nephrol, 2003, 23 (4):267-276.
[8] Ohga S, Shikata K, Yozai K, et al. Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-kappaB activation .Am J Physiol Renal Physiol, 2007,292 (4):1141-1150.
[9] Da Ros R, Assaloni R, Ceriello A. The preventive antioxidant action of thiazolidine- diones: a new therapeutic prospect in diabetes and insulin resistance. Diabet Med, 2004, 21(11):1249-1252.
[10] Bagi Z, Koller A, Kaley G. PPAR gamma activation, by reducing oxidative stress, increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes. Am J Physiol Heart Circ Physiol, 2004 ,286 (2) :H742-748.
[11] Sakai S,Miyauchi T,Irukayama Tomobe Y,et al. Peroxisome proliferatorsactiveateds141-1150.oform proteinsreceptor-gamma activators inhibitendothelin- 1-related cardiac hypertrophy in rats. Clin Sci, 2002, 103(48):16S-20S.
[12] Iglarz M,Touyz RM,Amiri F,et al.Effect of peroxisome proliferator-activated receptor-alpha and-gamma activators on vascular remodeling in endot helinde- pendent hypertension.Arteri Thromb Vasc Biol,2003,23(1):45-51.
[13] Pistrosch F, Herbing K, Kindel B, et al. Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction, andmicroalbuminuraof incipient diabetic nephropathy in patients. Diabetes, 2005, 54(7):2206-2211.
[14] Yu X,Li C,Li X,et al.Rosiglitazone prevents advanced glycation end products induced renal toxicity likely through suppression of plasminogen activator inhibitor
[15] Jones N, Blasutig IM, Eremina V, et al. Nck adaptor proteins linknephrin to the actin cytoskeleton of kidney podocytes. Nature, 2006, 440(7085):818-823.
[16]陈立平,周巧玲,欧阳春,等.罗格列酮对糖尿病肾病大鼠足细胞nephrin和podo -cin表达的影响.中华肾脏病杂志,2007 ,23(4) :263-264.
[17] Haneda M, Koya D, Kikkawa R. Cellular mechanisms in the development and progression of diabetic nephropathy : activation of the DAG-PKC-ERK pathway. Am J Kidney Dis, 2001, 38 (4 Suppl 1):S178-S181.
[18] Chang PC, Chen TH, Chang CJ, et al. Advanced glycosylation end products induce inducible nitric oxide synthase (iNOS) expression via a p38 MAPK-dependent pathway. Kidney Int , 2004 ,65 (5) :1664-1675.
[19] Verrier E, Wang L, Wadham C, et al. PPARgamma agonists ameliorate endothelial cell activation via inhibition of diacylglycerol-protein kinase C signaling pathway: role of diacylglycerol kinase. Circ Res, 2004, 94 (11) :1515 - 1522.
[2] Walter H,Lubben G. Potential role of oral thiazolidinedione therapy in preserving beta-cell function in type 2 diabetes mellitus [J].J Drugs,2005, 65 (1):1-13
[3] Barzilay J I , Abraham L,Heckbert S R, et al. The relation of markers of infla- mmation to the development of glucose disorders in the elderly: the Cardiovasc- ular Healt h Study [J].Diabetes,2001,50 (10) :2384-2389.
[4] Tsuruda T, Kato J, Sumi T, et al .Combined use of brain natriuretic peptide and C-reactive protein for predicting cardiovascular risk in outpatients with type 2 diabetes mellitus[J].Vasc Healt h Risk Manag , 2007,3 (4) :417-423.
[5] Bloomgarden Z T. Inflammation and insulin resistance [J].Diabetes Care, 2003, 26 (5):1619-1623.
[6]李秀钧,邬云红.糖尿病是一种炎症性疾病[J].中华内分泌代谢疾病杂志,2003, 19 (4):251-253.
[7] Pradhan AD, Manson J E, Rifai N, et al. C-reactive protein ,interleukin 6 and risk of developing type 2 diabetes mellitus [J].JAMA ,2001 ,286 (3) :327-334.
[8]吴伟华,张巾超,于江波,等. 2型糖尿病及合并大血管病变糖尿病患者C反应蛋白水平观察[J].中华内分泌代谢杂志,2003 ,19 (4):257-259.
[9]朱麒钱,尤巧英,李成江,等.C反应蛋白与2型糖尿病大血管病变危险因素的相关性研究[J] .中华内分泌代谢杂志,2005 ,21 (4):320-321.
[10] Koschinsky ML. Lipoprotein (a) and at herosclerosis: new perspectives on the me- chanism of action of an enigmatic lipoprotein [J].Curr At heroscler Rep, 2005, 7 (5):389-395.
[11] Lima LM, Carvalho MG, Loures-Vale AA, et al. Increased serum levels of lipo- protein (a) correlated wit h t he severity of coronary artery disease in patients submitted to angiography [J].Arq Bras Cardiol, 2006, 87(3):260-266.
[12] Cerrato P ,Lmperiale D, Fomengo P, et al .Higher lipoprotein(a) levels in at herot hrombotic than lacunar ischemic cerebrovascular disease [J].Neurology, 2002, 58(4):653-655.
[13] Tseng CH. Lipoprotein (a) is an independent risk factor forperipheral arterial disease in Chinese type 2 diabetic patients in Taiwan [J].Diabetes Care, 2004, 27 (2):517-521.
[14] Dieplinger B, Lingenhel A, Baumgartner N, et al . Increased serum lipoprotein (a) concent rations and low molecular weight phenotypes of apolipoprotein (a) are associated with symptomatic peripheral arterial disease [J].Clin Chem, 2007, 53 (7):1298-1305.
[15] Hunninghake DB, McGovern ME, Koren M. A dose–ranging study of a new,once-daily, dual-component drug product containing niacin extended release and lovastatin [J].Clin Cardiol,2003,26(3):112-118.
[16] Florkowski CM. Management of co-existing diabetes mellitus and dyslipidemia: defining the role of thiazo-lidinediones [J].Am J Cardiovasc Drugs, 2002,2(1):15 - 21.
[17] Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists [J].Diabetes,2005,54 (8):2460- 2470.
[18] Van Wijk JP, de Koning EJ, Martens EP, et al. Thiazolidinediones and blood lipids in type 2 diabetes [J].Arterioscler Thromb Vasc Biol,2003,23 (10):1744 - 1749.
[19] Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dysl- ipidemia [J].Diabetes Care,2005,28(7):1547-1554
[20] Khanderia U,Pop-Busui R, Eagle KA. Thiazolidinediones in type 2 diabetes: a cardiology perspective (October) [J].Ann Pharmacother,2008,42(10):1466-1474
[21] Kim HJ, Kim SK, ShimWS, Rosiglitazone improves insulin sensitivity with ince- ased serum leptin levels in patients with type 2 diabetes mellitus [J].Diabetes Res Clin Pract,2008,81(1):42-49.
[22] Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetesmellitus:peroxisomalp roliferator-activated receptor agonists provide a rational therapeutic approach [J].J Clin Endo-crinol Metab, 2004, (2):463-478.
[23] Barzilay JI, Abraham L, Heckbert SR, et al. The relation of markers of inflamm- ation to the development of glucose disorders in the elderly: the Cardiovascular Health Study [J].Diabetes, 2001, 50(10):2384- 2389.
[24] Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis.Circulation [J]. 2002,105(7):1135- 1143
[25] Hong G, Davis B, Khatoon N, et al. PPARgamma- dependent anti -inflammatory action of rosiglitazone in human monocytes: suppressionof TNF alpha secretion is not mediated by PTEN regulation [J].Biochem Biophys Res Commun,2003,303 (3):782- 787
[26] Martin DU, Pan RC, Despont JP. High-sensitivity C- reactive protein:a new risk factor of diabetes mellitus [J]. Rev Med Suisse Romande, 2004,122(3):163- 166.
[27] Spranger J, Kroke A, MohligM, et a1. Inflammatory cytokines and the risk to de- velop type 2 diabetes: results of the prospective population- based European Pro- spective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study [J].Diabetes, 2003,52 (3):812.
[28] Pickup JC, Mattock MB, Chusney GD, et a1. NIDDM as a disease of the innate immune system: association of acute– phase reactants and interleukin-6 with metabolic syndrome X [J].Diabetologia, 1997,40(11):1286-1230.
[29] Pradhan AD, Manson JE, Rifai N, et a1. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus [J].JAMA,2001, 22(3)286-327.
[30] Pistrosch F, HerbingK,Kindel B,et al . Rosiglitazone improves glomerular hyperf- iltration, renal endothelial dysfunction, andmicroalbuminura of incipient diabetic nephropathy in patients [J].Diabetes,2005,54(7):2206-2211.
[31] Katavetin P ,Eiam-Ong S ,Suwanwalaikorn S. Pioglitazone reduces urinary protein and urinary transforming growth factor- beta excretion in patients with type 2 diabetes and overt nephropathy [J].J Med Assoc Thai ,2006,89(2):170-177.
[32] Bakris GL ,Ruilope LM,McMorn SO, et al .Rosiglitazone reduces microalbumin uria and blood pressure independently of glycemia in type 2 diabetes patients with microalbuminuria [J].J Hypertens,2006,24(10):2047-2055.
[33] Leideig Bruckner G,ziegler R. Diabetes mellitus a risk for osteoporosis[J]. Exp clin Endocrinol Diabetes 2001; 109 (supplz):S493 -514.
[34]郭燕,黄兆民,孟俊非,等.非胰岛素依赖型糖尿病患者骨密度变化的探讨[J].中华放谢学杂志.1999 ,33 (10) :705-707.
[35] Goldstein BJ. Cliniacal translation of“a diabetes outcome progression trail”: ADOPT appropriate combination oral therapies in type 2 diabetes [J].J Clin Endocrinol Metab,2007,92 (4):1226-1228.
[36] Schwartz AV, Seumeyer DE, Vittinqhoff E, et al. Thiazolidinedione (TZDs) use and bone loss in older diabetic adults[J].J Clin EndocrinolMetab,2006,91(9): 3349-3354.
[37] Oxana PL, Sylwia OR,William RH, et al. Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone [J].Endocrinology,2007,148 (6): 2669- 2680.
[38]李红兵,杨金奎,李毅斌,等,罗格列酮钠对非增生性糖尿病视网膜病变的作用[J].首都医科大学学报,2009,30(4):460-462.
[39] Dormandy JA, CharbonnelB, Eckland DJ, et al. Secondary prevention of macro vascular events in patientswith type 2 diabetes in the PROactive Study (PRO spective pioglitAzone Clinical Trial In macroVascular Events): a randomized controlled trial [J].Lancet,2005,366:1279-1289.
[40]李光伟,王金平,李春梅,等.胰岛素增敏剂罗格列酮抗高血压作用探讨[J].中华内科杂志, 2004, 43: 907-910.
[41] Schernthaner G, MatthewsDR, Charbonnel B, et al. Efficacy and safety of pioglit- azone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial [J].J Clin Endocrinol Metab,2004,89(12):6068-6076.
[42] Tan M, Johns D, González Gálvez G, et al. Effects of pioglitazone and glimepiride on glycemic control and insulin sensitivity in Mexican patients with type 2 diabetesmellitus: A multicenter, randomized, double-blind, parallel-group trial [J]. Clin Ther,2004,26 (5): 680-693.
[43] Raskin P, McGill J, SaadMF, et al. Combination therapy for type 2 diabetes:rep- aglinide plus rosiglitazone [J].Diabet Med,2004,21(4):329-335.
[44] Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Asso- ciation andAmerican Diabetes Association [J].Diabetes Care,2004,27 (1):256-263.
[45] Rosenstock J, Einhorn D, Hershon K, et al. Efficacy and safety of pioglitazone in type 2 diabetes: a randomised, placebo-controlled study in patients receiving stable insulin therapy [J].Int J Clin Pract,2002,56 (4):251-257.
[46] Berlie HD, Kalus JS, Jaber LA. Thiazolidinediones and the risk of edema: a meta analysis [J].Diabetes Res Clin Pract,2007,76(2):279-289.
[47]文迪雅Ⅳ期临床研究协作组,罗格列酮治疗2型糖尿病的临床观察[J].中华内科杂志,2003 ,42 (9) :636-638.
[48] Hussein Z,Wentworth JM,Nankervis AJ , et al. Effectiveness and side effects of thiazolidinediones for type 2 diabetes : real-life experience from a tertiary hospital [J] .Med J Aust,2004,181(10) :536-539
[49] Fonsece V,Effect of thiazolidinediones on body weight in patients with diabetes mellitus [J].AmJ Med,2003,115(8):42～48.
[1] Sato K,Sugawara A,Kudo M,et al.Expression of peroxisome proliferator activated receptor isoform proteins in the rat kidney. Hypertens Res, 2004, 27(6):417-425.
[2] Turtle KR.Linking metabolism and immunology:diabetic nephropathy is an inflammatory disease.J Am Soc Nephrol,2005,16:1537-1538
[3] Lee S, Kim W, Kang KP, et al. Agonist of peroxisome proliferators-activated rece- ptor gamma, rosiglitazone, reduces renal injury and dysfunction in a murine sep- sis model. Nephrol Dial Transplant, 2005, 20 (6): 1057-1065
[4] Agarwal R Anti-inflammatory effects of shortterm pioglitazone therapy in men with advanced diabetic nephropathy. Am J Physiol Renal Physiol, 2006, 290(3): F600- F605.
[5] Haraguchi K, Shimura H, Onaya T. Suppression of experimental crescentic glome- rulo nephritis by peroxisome proliferator-activated receptor gamma activators.Clin Exp Nephrol, 2003,7(1):27-32.
[6] BenigniA, Zoja C, Tomasoni S, et al. Transcrip tional regulation of nephrin gene by peroxisome proliferator-activated receptor-gamma agonist: molecularmechanism of the antiproteinuric effect of pioglitazone. J Am Soc Nephrol, 2006, 17 (6):1624- 1632.
[7] Sivarajah A, Chatterjee PK, PatelNS, et al. Agonists of peroxisome proliferator activated receptor-gamma reduce renal ischemia / reperfusion injury.Am J Nephrol, 2003, 23 (4):267-276.
[8] Ohga S, Shikata K, Yozai K, et al. Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-kappaB activation .Am J Physiol Renal Physiol, 2007,292 (4):1141-1150.
[9] Da Ros R, Assaloni R, Ceriello A. The preventive antioxidant action of thiazolidine- diones: a new therapeutic prospect in diabetes and insulin resistance. Diabet Med, 2004, 21(11):1249-1252.
[10] Bagi Z, Koller A, Kaley G. PPAR gamma activation, by reducing oxidative stress, increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes. Am J Physiol Heart Circ Physiol, 2004 ,286 (2) :H742-748.
[11] Sakai S,Miyauchi T,Irukayama Tomobe Y,et al. Peroxisome proliferatorsactiveateds141-1150.oform proteinsreceptor-gamma activators inhibitendothelin- 1-related cardiac hypertrophy in rats. Clin Sci, 2002, 103(48):16S-20S.
[12] Iglarz M,Touyz RM,Amiri F,et al.Effect of peroxisome proliferator-activated receptor-alpha and-gamma activators on vascular remodeling in endot helinde- pendent hypertension.Arteri Thromb Vasc Biol,2003,23(1):45-51.
[13] Pistrosch F, Herbing K, Kindel B, et al. Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction, andmicroalbuminuraof incipient diabetic nephropathy in patients. Diabetes, 2005, 54(7):2206-2211.
[14] Yu X,Li C,Li X,et al.Rosiglitazone prevents advanced glycation end products induced renal toxicity likely through suppression of plasminogen activator inhibitor
[15] Jones N, Blasutig IM, Eremina V, et al. Nck adaptor proteins linknephrin to the actin cytoskeleton of kidney podocytes. Nature, 2006, 440(7085):818-823.
[16]陈立平,周巧玲,欧阳春,等.罗格列酮对糖尿病肾病大鼠足细胞nephrin和podo -cin表达的影响.中华肾脏病杂志,2007 ,23(4) :263-264.
[17] Haneda M, Koya D, Kikkawa R. Cellular mechanisms in the development and progression of diabetic nephropathy : activation of the DAG-PKC-ERK pathway. Am J Kidney Dis, 2001, 38 (4 Suppl 1):S178-S181.
[18] Chang PC, Chen TH, Chang CJ, et al. Advanced glycosylation end products induce inducible nitric oxide synthase (iNOS) expression via a p38 MAPK-dependent pathway. Kidney Int , 2004 ,65 (5) :1664-1675.
[19] Verrier E, Wang L, Wadham C, et al. PPARgamma agonists ameliorate endothelial cell activation via inhibition of diacylglycerol-protein kinase C signaling pathway: role of diacylglycerol kinase. Circ Res, 2004, 94 (11) :1515 - 1522.