糖尿病肾脏病病人的血糖控制幻灯片.ppt

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1、糖尿病肾脏病病人的血糖控制糖尿病肾脏病病人的血糖控制第1页，共60页，编辑于2022年，星期一大纲大纲目前已经存在的在糖尿病肾脏病病人中目前已经存在的在糖尿病肾脏病病人中的血糖控制效果的证据的血糖控制效果的证据肾功能基本正常的肾功能基本正常的1 1和和2 2型糖尿病病人型糖尿病病人 透析前的病人透析前的病人 HDHD和和PDPD的病人的病人 目前已经建议的糖尿病肾脏病病人血糖目前已经建议的糖尿病肾脏病病人血糖控制的方法控制的方法降糖药物的治疗降糖药物的治疗胰岛素治疗胰岛素治疗可能的研究领域可能的研究领域第2页，共60页，编辑于2022年，星期一Intensive treatment of hy

2、perglycemia prevents DKD and may slow the progression of established kidney disease Lowering HbA1c levels to approximatelyLowering HbA1c levels to approximately7.0%reduces the development of7.0%reduces the development ofmicroalbuminuria.(Strong)microalbuminuria.(Strong)Lowering HbA1c levels to appro

3、ximately 7.0%reduces the development of macroalbuminuria.(Moderate)Lowering HbA1c levels to approximately 7.0%Lowering HbA1c levels to approximately 7.0%reduces the rate of decrease in GFR.reduces the rate of decrease in GFR.(Weak)KDOQI Clinical Practice Guidelines and Clinical Practice Recommendati

4、ons forKDOQI Clinical Practice Guidelines and Clinical Practice Recommendations forDiabetes and Chronic Kidney Disease:Diabetes and Chronic Kidney Disease:Am J Kidney Dis 49:S1-S180,2007(suppl 2)第3页，共60页，编辑于2022年，星期一第4页，共60页，编辑于2022年，星期一Effect of Glycemic Control on Kidney Function and Albuminuria i

5、n Effect of Glycemic Control on Kidney Function and Albuminuria in Type 1 Diabetes 第5页，共60页，编辑于2022年，星期一The Diabetes Control and Complications Trial:DCCT Study design:Study design:a multicentera multicenter，randomized clinical trialrandomized clinical trial ParticipantsParticipants：1441 patients wit

6、h type 1 diabetes1441 patients with type 1 diabetes Group:Group:primary-prevention cohortprimary-prevention cohort：726 with no retinopathy726 with no retinopathy secondary-intervention cohortsecondary-intervention cohort：715 with mild retinopathy 715 with mild retinopathy InterventionIntervention：in

7、tensive therapyintensive therapy ：administered either with an external insulin pump or administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood by three or more daily insulin injections and guided by frequent blood glucose monitoring

8、 glucose monitoring conventional therapyconventional therapy ：one or two daily insulin injections one or two daily insulin injections Followed for a mean of Followed for a mean of 6.5 years6.5 years Main Outcome Measures:Main Outcome Measures:appearance and progression of retinopathy and appearance

9、and progression of retinopathy and other complicationsother complications第6页，共60页，编辑于2022年，星期一DCCT-Measurements of Glycosylated Hemoglobin and Blood DCCT-Measurements of Glycosylated Hemoglobin and Blood Glucose in Patients with IDDM Receiving Intensive or Glucose in Patients with IDDM Receiving Int

10、ensive or Conventional Therapy Conventional Therapy TheDiabetesControlandComplicationsTrialResearchGroup:Theeffectofintensivetreatmentofdiabetesonthedevelopmentandprogressionoflong-termcomplicationsininsulin-dependentdiabetesmellitus.NEnglJMed329:977-986,1993第7页，共60页，编辑于2022年，星期一DCCTDCCT56%43%34%The

11、 Diabetes Control and Complications Trial Research Group:The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.N Engl J Med 329:977-986,1993primary-prevention cohortsecondary-intervention cohort第8页，共60页，编辑于2

12、022年，星期一The Epidemiology of Diabetes Interventions and Complications:EDIC study Study designStudy design:Observational study begun in 1993(following:Observational study begun in 1993(following DCCT closeout)in 28 medical centers in the United States DCCT closeout)in 28 medical centers in the United

13、States and Canada.and Canada.During the EDIC study:During the EDIC study:glycemic levels no longer differed glycemic levels no longer differed substantiallysubstantiallyParticipants:1349(of 1375)EDIC volunteersParticipants:1349(of 1375)EDIC volunteers who had who had kidney evaluation at years 7 or

14、8kidney evaluation at years 7 or 8Main Outcome Measures：Development of microalbuminuria,clinical-grade albuminuria,hypertension,or increase in serum creatinine level.第9页，共60页，编辑于2022年，星期一EDICEDICSustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of dia

15、betic nephropathy:The Epidemiology of Diabetes Interventions and Complications(EDIC)Study.JAMA 290:2159-2167,2003第10页，共60页，编辑于2022年，星期一EDICEDIC第11页，共60页，编辑于2022年，星期一EDICEDICDevelop hypertension:intensive treatment group 29.9%conventional-treatment:40.3%;P001.A serum creatinine level of 2 mg/dL or gr

16、eater intensive-treatment vs the conventional-treatment group(5 vs 19,P=.004)Required dialysis and/or transplantationfewer patients experienced either of these outcomes in the intensive group(4 vs 7,P=0.36).第12页，共60页，编辑于2022年，星期一Effect of Glycemic Control on Kidney Function and Effect of Glycemic Co

17、ntrol on Kidney Function and Albuminuria in Albuminuria in Type 2 DiabetesType 2 Diabetes第13页，共60页，编辑于2022年，星期一The Kumamoto Study Study design:a randomized clinical triala randomized clinical trial Participants Participants 110110 Japanese patients with type 2 diabetestype 2 diabetes Group:Group:the

18、 primary prevention cohort:55 with no retinopathy the primary prevention cohort:55 with no retinopathy the secondary intervention cohort:55 with simple retinopathy the secondary intervention cohort:55 with simple retinopathy Intervention:Intervention:multiple insulin injection therapy(multiple insul

19、in injection therapy(MITMIT)groups(administered three)groups(administered three or more daily insulin injections)or more daily insulin injections)conventional insulin injection therapy(conventional insulin injection therapy(CIT)CIT)groups(administered one groups(administered one or two daily interme

20、diate-acting insulin injections)or two daily intermediate-acting insulin injections)Follow up:8 years 8 years Main Outcome Measures:Worsening of microvascular Worsening of microvascular complications complications 第14页，共60页，编辑于2022年，星期一43.5%11.5%Shichiri M,Kishikawa H,Ohkubo Y,Wake N:Long-term resul

21、ts of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients.Diabetes Care 23:B21-B29,2000(suppl 2)The Kumamoto StudyThe Kumamoto Study40%16%Secondary intervention cohortPrimary prevention cohort第15页，共60页，编辑于2022年，星期一The Kumamoto Study The Kumamoto Study glycemic threshold to pre

22、vent the onset and progression of diabetic microvascular complications was as follows:HbA1c 6.5%,fasting blood glucose concentration 110 mg/dl,2-h postprandial blood glucose concentration 180 mg/dl 第16页，共60页，编辑于2022年，星期一UKPDS UKPDS Study design:Study design:randomized clinical trialrandomized clinic

23、al trial Participants:Participants:38673867 newly diagnosed patients with type 2 diabetesnewly diagnosed patients with type 2 diabetes Intervention:Intervention:intensive managementintensive management using a sulfonylurea or insulin using a sulfonylurea or insulin conventional managementconventiona

24、l management with diet alone with diet alone EndpointsEndpoints:Three aggregate endpoints:Three aggregate endpoints any diabetes-related endpointany diabetes-related endpoint(sudden death,death from hyperglycaemia or (sudden death,death from hyperglycaemia or hypoglycaemia,fatal or non-fatal myocard

25、ial infarction,angina,heart failure,stroke,hypoglycaemia,fatal or non-fatal myocardial infarction,angina,heart failure,stroke,renal failure,amputation,vitreous haemorrhage,retinopathy requiring renal failure,amputation,vitreous haemorrhage,retinopathy requiring photocoagulation,blindness in one eye,

26、or cataract extraction);photocoagulation,blindness in one eye,or cataract extraction);diabetes-related deathdiabetes-related death(death from myocardial infarction,stroke,peripheral vascular (death from myocardial infarction,stroke,peripheral vascular disease,renal disease,hyperglycaemia or hypoglyc

27、aemia,and sudden death);disease,renal disease,hyperglycaemia or hypoglycaemia,and sudden death);all-cause mortalityall-cause mortality UK Prospective Diabetes Study(UKPDS)Group:Intensive blood-glucose control with sulphonylureas orinsulin compared with conventional treatment and risk of complication

28、s in patients with type 2 diabetes(UKPDS 33).Lancet 352:837-853,1998第17页，共60页，编辑于2022年，星期一UKPDSUKPDSAfter 9 years of intensive therapy RR reduction for the development of microalbuminuria was 24%(P=0.0006)RR reduction for the development of macroalbuminuria with insulin or sulfonylureas was 33%at 9

29、years(4.4%versus 6.5%,intensive versus conventional),but this finding was not statistically significant67%risk reduction for a doubling of plasma creatinine levels at 9 years(0.71%of the intensive group and 1.76%of the conventional group;P=0.027).第18页，共60页，编辑于2022年，星期一UKPDSUKPDS the risk in the inte

30、nsive group was the risk in the intensive group was 12%lower12%lower(p=0.029)(p=0.029)for any for any diabetes-related endpointdiabetes-related endpoint 10%10%lower lower（p=0.34p=0.34)for any diabetes-related death;)for any diabetes-related death;6%6%lower(p=0.44)for all-cause mortality.for all-caus

31、e mortality.Patients in the intensive group had more hypoglycaemic Weight gainWeight gain was significantly higher in the intensive was significantly higher in the intensive group(mean 2.9 kg)than in the conventional group group(mean 2.9 kg)than in the conventional group(p0.001)(p8.6HbA18.6第21页，共60页

32、，编辑于2022年，星期一Studies shown adequate glycaemic control in diabetic Studies shown adequate glycaemic control in diabetic predialysis CRF patients can reduce morbidity and mortality predialysis CRF patients can reduce morbidity and mortality in the first years following the start of dialysisin the firs

33、t years following the start of dialysis Yu CC,et al.Predialysis glycemic control is an independent Yu CC,et al.Predialysis glycemic control is an independent predictor of clinical outcome in type II diabetics on continuous predictor of clinical outcome in type II diabetics on continuous ambulatory p

34、eritoneal dialysis.Perit Dial Int 1997;17:262268.ambulatory peritoneal dialysis.Perit Dial Int 1997;17:262268.Wu MS,et al Pre-dialysis glycemic control is an independent predictor Wu MS,et al Pre-dialysis glycemic control is an independent predictor of mortality in type II diabetic patients on conti

35、nuous ambulatory of mortality in type II diabetic patients on continuous ambulatory peritoneal dialysis.Perit Dial Int 1999;19(Suppl.2):S179S183.peritoneal dialysis.Perit Dial Int 1999;19(Suppl.2):S179S183.Suzuki Y,Arakawa M.,Gejyo F and Collaborative Study Group.Suzuki Y,Arakawa M.,Gejyo F and Coll

36、aborative Study Group.The treatment of the uraemic diabetic.Are we doing enough?A The treatment of the uraemic diabetic.Are we doing enough?A view from Japan:Fumitake Gejyo and Collaborate Study Group.view from Japan:Fumitake Gejyo and Collaborate Study Group.Nephrol Dial Transplant 1995;10(Suppl.7)

37、:4755.Nephrol Dial Transplant 1995;10(Suppl.7):4755.第22页，共60页，编辑于2022年，星期一Glycaemic control in HD patientsMorioka T,Emoto M,Tabata T,et al:Glycemic control is a predictor of survival for diabetic patients on hemodialysis.Diabetes Care 24:909-913,2001第23页，共60页，编辑于2022年，星期一Takeshi Oomichi,etal；Impact

38、of Glycemic Control on Survival of Diabetic Patients on Chronic Regular Hemodialysis:A 7-year observational study DiabetesCare29:1496-1500；2006Glycaemic control in HD patients第24页，共60页，编辑于2022年，星期一Glycaemic control in HD patientsKalantar-Zadeh K,et al:A1C and survival in maintenance hemodialysis pat

39、ients.Diabetes Care 30:1049-1055,2007第25页，共60页，编辑于2022年，星期一Glycaemic control in PD patientsIn 2452 diabetic PD no association between A1c and survival in unadjusted or diverse levels of multivariate adjusted model Perit Dial Int 27(Supplement_3):21-2007第26页，共60页，编辑于2022年，星期一Management of hyperglycem

40、ia in diabetes and chronic kidney disease第27页，共60页，编辑于2022年，星期一血糖的控制血糖的控制血糖的评估血糖的评估降糖目标及检测频率降糖目标及检测频率降糖治疗降糖治疗降糖药物降糖药物胰岛素胰岛素第28页，共60页，编辑于2022年，星期一血糖的评估血糖的评估 自我监测血糖（自我监测血糖（自我监测血糖（自我监测血糖（SMBGSMBG）指导病人进行指导病人进行指导病人进行指导病人进行SMBGSMBGSMBGSMBG，并且规律的针对对病人对技术掌握的，并且规律的针对对病人对技术掌握的，并且规律的针对对病人对技术掌握的，并且规律的针对对病人对技术掌握

41、的能力以及病人对这些数据利用能力进行的评估能力以及病人对这些数据利用能力进行的评估能力以及病人对这些数据利用能力进行的评估能力以及病人对这些数据利用能力进行的评估 对病人血糖控制情况的评估应该综合考虑病人自我监测血对病人血糖控制情况的评估应该综合考虑病人自我监测血对病人血糖控制情况的评估应该综合考虑病人自我监测血对病人血糖控制情况的评估应该综合考虑病人自我监测血糖和最近糖和最近糖和最近糖和最近HbA1cHbA1cHbA1cHbA1c的结果的结果的结果的结果糖化血红蛋白（糖化血红蛋白（HbA1cHbA1cHbA1cHbA1c）HbA1cHbA1cHbA1cHbA1c不仅反映病人过去不仅反映病人过

42、去不仅反映病人过去不仅反映病人过去2-32-32-32-3个月血糖的情况，而且也可以个月血糖的情况，而且也可以个月血糖的情况，而且也可以个月血糖的情况，而且也可以用来检测病人血糖仪的准确性以及自我监测血糖计划的用来检测病人血糖仪的准确性以及自我监测血糖计划的用来检测病人血糖仪的准确性以及自我监测血糖计划的用来检测病人血糖仪的准确性以及自我监测血糖计划的充分性充分性充分性充分性 持续血糖监测持续血糖监测持续血糖监测持续血糖监测 (Continuous glucose monitoring)(Continuous glucose monitoring)(Continuous glucose mon

43、itoring)(Continuous glucose monitoring)第29页，共60页，编辑于2022年，星期一降糖目标及检测频率降糖目标及检测频率KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease:Kidney Dis

44、ease:Am J Kidney Dis 49:S1-S180,2007(suppl 2)第30页，共60页，编辑于2022年，星期一Noninsulin Hypoglycemic Agents for Management of Hyperglycemia in CKDInsulin SecretagoguesSulfonylureasNonsulfonylurea Insulin Secretagogues(glinides)Incretin-Based Insulin SecretagoguesInsulin SensitizersBiguanidesThiazolidinediones

45、Other Medications-Glucosidase Inhibitors第31页，共60页，编辑于2022年，星期一Sulfonylureasbinding to the SU receptor 1 of cellstimulate insulin secretion Blood Glucose Most Affected：Fasting and postprandial第32页，共60页，编辑于2022年，星期一SulfonylureasKDOQI Clinical Practice Guidelines and Clinical Practice Recommendations f

46、orKDOQI Clinical Practice Guidelines and Clinical Practice Recommendations forDiabetes and Chronic Kidney Disease:Diabetes and Chronic Kidney Disease:Am J Kidney Dis 49:S1-S180,2007(suppl 2)第33页，共60页，编辑于2022年，星期一Nonsulfonylurea Insulin Secretagogues(glinides)Bind to SU receptor in pancreatic cell(di

47、fferent than SU site)stimulate insulin releasea very short half-life and duration of action(3-4 hours)-administered shortly before mealsrelatively low risk of hypoglycemiaBlood Glucose Most Affected：Postprandial第34页，共60页，编辑于2022年，星期一glinides瑞格列奈：No data for patients with creatinineclearance 20 ml/mi

48、n第35页，共60页，编辑于2022年，星期一Incretin-Based Insulin SecretagoguesThe incretin(肠降血糖素)composed primarily of 2 peptides;glucose-dependent insulinotropic polypeptide glucose-dependent insulinotropic polypeptide glucagon-like peptide 1(GLP-1)glucagon-like peptide 1(GLP-1)Effect by intestinally derived peptides

49、 which are released in the presence of glucose or nutrients in the gutaugmentation of glucose-stimulated insulin secretion 第36页，共60页，编辑于2022年，星期一Incretin-Based Insulin SecretagoguesIncretins are rapidly inactivated by enzyme DPP 4(二肽基肽酶4)resulting in a very short half-life(minutes)The incretin pathw

50、ay appears to be attenuated in patients with type 2 diabetes,making the pathway a target for the development of new pharmacological2 approved agentsExenatide(艾塞那肽)Sitagliptin(西他列汀)第37页，共60页，编辑于2022年，星期一Incretin-Based Insulin Secretagogues：Exenatide(艾塞那肽艾塞那肽)a glucagon-like peptide 1(GLP-1)receptor a