餐后血糖从被忽略到重视green salon

1、人类认识、挑战疾病的典范人类认识、挑战疾病的典范“餐后血糖餐后血糖” ” 从忽略到共从忽略到共识识目 录从ADA十年态度的转变到IDF餐后血糖指南颁布人类对PPG重要性的认识的进步拜唐苹作用于餐后血一糖而又超越餐后高血糖的新信息ADA指南对餐后血糖认识的演变ADA 1997ADA 2003ADA 2005ADA 2007Although the OGTT is an acceptable diagnostic test and has been an invaluable tool in research, it is not recommend for routine use. Becaus

2、e of its inconvenience to patients that it is unnecessary, the OGTT is already not widely used for diagnosing diabetes.Although the OGTT(which consists of an FPG and 2-h PG value) was recognized as a valid way to diagnose diabetes, the use of the test for diagnostic purposes in clinical practice was

3、 discouraged for several reasons(e.g. inconvenience, less reproducibility, greater cost)Either an FPG test or 2-h OGTT (75-g glucose load) is appropriate (B)The FPG is the preferred test to screen for pre-diabetes and diabetes. The OGTT may also be used to screen for pre-diabetes or diabetes in high

4、-risk adults. (E)To screen for diabetes/pre-diabetes, either an FPG test or 2-h OGTT (75-g glucose load) or both are appropriate.(B)An OGTT may be considered in patients with IFG to better define the risk of diabetes. (E)American Diabetes Association: Change in position on PGR 2001: “There are insuf

5、ficient data either to support or refute the need for extensive or routine PPG monitoring in diabetes, except in the setting of pregnancy.”1 2006: “Elevated postchallenge (2-h OGTT) glucose values have been associated with increased cardiovascular risk independent of FPG in some epidemiological stud

6、ies There are now pharmacological agents that primarily modify PPG and thereby reduce A1C in parallel. Thus, in individuals who have premeal glucose values within target but who are not meeting A1C targets, consideration of monitoring PPG 12 h after the start of the meal and treatment aimed at reduc

7、ing PPG values 180 mg/dl may lower A1C.”21. ADA clinical practice recommendations 2001. Diabetes Care 2001; 28:S1S133.2. ADA clinical practice recommendations 2005. Diabetes Care 2006; 29:S4S42.What do guidelines recommend for the treatment of dysglycaemia?Western Pacific Diabetes Declaration (WPDD)

8、 guidelines:1“The risk of complications is related to the duration of diabetes, as well as the degree of hyperglycaemia. However, due to delayed diagnosis, these complications may already be present at diagnosis”International Diabetes Federation Western Pacific Region (IDF-WPR) practical targets and

9、 treatments:2“Recent studies have shown the potential for intervention in IGT patients toreduce progression to type 2 diabetes”Therefore, early diagnosis of hyperglycaemia at the prediabetes stage is essential to reduce the human and economic costs of type 2 diabetes and associated complications1. W

10、PDD 2002. .2. IDF-WPR 2005. . Organisations recommendations for PPG targets1-2 h PP10.0 mmol/L180 mg/dLADA 200652 h PP5.0-10.0 mmol/L90-180 mg/dLCDA 20034Unspecified4.0-7.5 mmol/L70-135 mg/dLEuropean Cardiovascular Prevention Guidelines, 200432 h PP8.0 mmol/L140 mg/dLAACE/ACE, 200521-2 h PP8.0 mmol/

11、L145 mg/dLIDF 20051TimingTimingPPG target valuesPPG target valuesOrganizationOrganizationPP = postprandialIDF Global guidelines 2005. GGT2D.pdf. AACE/ACE consensus statement. July 8, 2005.3. de Backer et al. Neurologia 2004;19:440450.4. CDA clinical practice guidelines. Can J Diabetes 2003; 27:S1S15

12、1.5. ADA clinical practice recommendations. Diabetes Care 2006; 29:S4S42. GUIDELINE FOR MANAGEMENT OF POSTMEAL GLUCOSEA New Guideline of the International Diabetes Federation200720072007年年IDFIDF餐后血糖管理指南餐后血糖管理指南确立了确立了PPGPPG的地位的地位餐后高血糖是否有害？餐后高血糖是否有害？Yes治疗餐后高血糖是否有益？治疗餐后高血糖是否有益？Yes如何有效控制餐后高血糖？如何有效控制餐后高血

13、糖？Clear餐后血糖控制目标及其监测餐后血糖控制目标及其监测In detialQuestion #1:Is postmeal hyperglycaemia harmful? Major Evidence:Postmeal and postchallenge hyperglycaemia are independent risk factors for macrovascular disease4 Balkau B et al. Diabetes Care 19985 Hanefeld M et al. Diabetologia 19966 Barrett-Connor E et al. Di

14、abetes Care 19987 Donahue R. Diabetes 19871 DECODE Study Group. Lancet 19992 Shaw J et al. Diabetologia 19993 Tominaga M et al. Diabetes Care 1999多项研究证实：多项研究证实：餐后高血糖与心血管危险密切相关餐后高血糖与心血管危险密切相关DECODE 19991太平洋和印度洋 19992Funagata 糖尿病研究 19993白厅、巴黎和赫尔新基研究 19984糖尿病干预研究 19965RanchoBernardo 研究19986檀香山 心脏计划 198

15、77Risk of Macrovascular Disease is Correlated with FPG 2 hr PPPG and HbA1c and Shows no ThresholdYudkin and Oswald Diabetic Medicine 4:13-18, 1987Yudkin and Oswald Diabetic Medicine 4:13-18, 1987Kuusisto et alKuusisto et al Diabetes 43:960-967, 1994 Diabetes 43:960-967, 1994Standl et alStandl et al

16、Diabetologia 39:1540-1545, 1996 Diabetologia 39:1540-1545, 1996LaaksoLaakso Diabetes 48:937-942, 1999 Diabetes 48:937-942, 1999GersteinGerstein Diabetes Care 22:659-660, 1999 Diabetes Care 22:659-660, 1999HaffnerHaffner Endocrine Reviews 19:583-592,1998 Endocrine Reviews 19:583-592,1998Grundy et alG

17、rundy et al Circulation 100:1134-1146, 1999 Circulation 100:1134-1146, 1999IGT IGT 与动脉硬化与动脉硬化 - - 来自来自301301医院的研究医院的研究*IGTNGTDMIGTIGTNGTNGTDMDMN: 97(NGT), 51(IGT), 73(DM)校正年龄和性别校正年龄和性别* P0.05, P0.005, v.s. NGTJing WS, Pan CY, Lu JM, et al.Chin J Endocrinol & Metab 2004;20(2):136-139 Angiographic

18、 coronary disease progression as measured by change in minimum coronary luminal diameter. Data from Mellen et al. Diabet Med 24:1156-1159, 2007. Diabetes Care 2007; 30:263-Reference in Detial? I didnt find in you file you send餐后血糖升高早于空腹血糖餐后血糖升高早于空腹血糖对不同时段高血糖的认识对不同时段高血糖的认识8%HbA1c9% HbA1c9% 7%HbA1c8%

19、6.5%HbA1c7% HbA1c=7.0&2h-PG=11.12h-PG=11.1FPG=7.0 20-29 30-39 40-49 50-59 60-69 70-0.41.92.75.17.48.9新诊断新诊断2 2型糖尿病患者型糖尿病患者餐后血糖升高为主餐后血糖升高为主J WP.Diabetologia,2007 Feb;50(2):286欧洲欧洲/ /中国心脏调查：中国心脏调查：仅查仅查FPGFPG糖尿病的漏诊率很高糖尿病的漏诊率很高人群比例 (%)正常血糖空腹血糖受损糖耐量低减2型糖尿病020406080100OGTTOGTT空腹血糖空腹血糖急诊入院择期入院漏诊漏诊OGTTO

20、GTT空腹血糖空腹血糖急诊入院择期入院020406080100漏诊漏诊人群比例 (%)301301医院：医院：FBGFBG与与PBGPBG对新诊断糖代谢异常的比较对新诊断糖代谢异常的比较 WHO(%)WHO(%)ADA(%)ADA(%)差值差值(%)(%)DM196（16.3)38(3.16)+13.1IGT462(38.4)-IFG?-61(5.1)NGT546(45.4)1105(91.6)46.2 空腹血糖与餐后血糖均诊断空腹血糖与餐后血糖均诊断DM的仅有的仅有30例（例（30/204，14.7） 餐后血糖诊断餐后血糖诊断DM的阳性率高的阳性率高(n=196) 空腹血糖诊断空腹血糖诊断D

21、M的阳性率低的阳性率低(n=38) 只查只查FBG，DM漏诊漏诊158人，人，85% Reference?Relative Changes in FPG and 2hr PG as HbA1c IncreasesWoerle et al. 2004糖尿病高危个体葡萄糖水平的升高过程糖尿病高危个体葡萄糖水平的升高过程 Pavkov ME, et al. Diabetes Care. 2007 Jul;30(7):1758-63初期：初期：相当长的时间里呈相当长的时间里呈缓慢线性升高缓慢线性升高后期：后期：在短期内以指数速在短期内以指数速度迅速升高，并达度迅速升高，并达到糖尿病诊断标准到糖尿病诊断

22、标准OGTTOGTT负荷后负荷后2 2小时血糖水平小时血糖水平Ceriello A, Diabetes Care 2003HyperglycemiaO2-PKCO2-NAD(P)H oxidasePeroxynitriteNF-kBiNOS eNOSNONitrotyrosineDNA damageGAPDHNAD+Adhesion moleculesProinflammatory CytokinesPARPEndothelial disfunctionPolyol PathwayAGE FormationHexosamine FluxDiabetic ComplicationsMitocho

23、ndriaQUESTION 1:Is postmeal hyperglycaemia harmful?Postmeal and postchallenge hyperglycaemia are independent risk factors for macrovascular disease.Level 1+Other Evidence Statements: Postmeal hyperglycaemia is associated with increased risk of retinopathy.Level 2+ Postmeal hyperglycaemia is associat

24、ed with increased carotid intima-media thickness (IMT).Level 2+Postmeal hyperglycaemia causes oxidative stress, inflammation and endothelial dysfunction.Level 2+Postmeal hyperglycaemia is associated with decreased myocardial blood volume and myocardial blood flow.Level 2+Postmeal hyperglycaemia is a

25、ssociated with increased risk of cancer.Level 2+ Postmeal hyperglycaemia is associated with impaired cognitive function in elderly people with type 2 diabetes.Level 2+ Recommendation: Postmeal hyperglycaemia is harmful and should be addressedEvidence Statements:Treatment with agents that target post

26、meal plasma glucose reduces vascular events.Level 1-Targeting both postmeal and fasting plasma glucose is an important strategy for achieving optimal glycaemic control.Level 2+ QUESTION 2: s treatment of postmeal hyperglycaemia beneficial?糖尿病病程（年）糖尿病病程（年）*IGT = 糖耐量异常肥胖肥胖 IGT* 糖尿病糖尿病 症状性高血糖症状性高血糖 -细胞

27、细胞 功能功能 (%)-150 5 10 15 20 25 30 血浆葡萄糖血浆葡萄糖 (mg/dL)胰岛素抵抗胰岛素抵抗胰岛素水平胰岛素水平空腹血糖空腹血糖餐后血糖餐后血糖25020015010050035030025020015010050-10-5 T2DM首先出现餐后高血糖尽可能长期治疗尽可能长期治疗尽可能早诊断、早治疗尽可能早诊断、早治疗HbA1c6%HbA1c6%以下的血糖异常者，以下的血糖异常者，主要表现为餐后高血糖高主要表现为餐后高血糖高Arch Intern Med 164:16271632, 2004 Contributes More to HbA1c than FPG a

28、t HbA1cs Below 8.5%餐后血糖达标有助于提高总体血糖达标率餐后血糖达标有助于提高总体血糖达标率HbA1c达标（达标（7.0%）Diabetes Research and Clinical Practice2007;77:280我国目前我国目前HbA1cHbA1c控制水平控制水平7.67.6中国糖尿病健康管理调查中国糖尿病健康管理调查 1998 1998华北、华南、华东、华西和东北华北、华南、华东、华西和东北5 5 个地区个地区49 49 家市级中心医院家市级中心医院参与分析的患者参与分析的患者 2246 2246 例例中国糖尿病健康管理调查中国糖尿病健康管理调查 2006 20

29、06中国中国1818个城市个城市6060家医院登记治疗家医院登记治疗超过超过1212个月的糖尿病患者个月的糖尿病患者参与分析的患者参与分析的患者 2702 2702 例例达标率达标率%25.9%29.5%44.6%010%20%30%40%50%6.5%7.5%达标率达标率%25%35%010%20%30%40%50%6.5%7.5%40%PanCY,YangWY, Jia WP,et al Diabetes 2008, Supp.?潘长玉等中华内分泌代谢杂志潘长玉等中华内分泌代谢杂志20:420-424,200420:420-424,2004平均平均HbA1c：7.6%平均平均HbA1c：7

30、.7%41%20072007年年IDFIDF餐后血糖管理指南餐后血糖管理指南餐后高血糖是否有害？餐后高血糖是否有害？治疗餐后高血糖是否有益？治疗餐后高血糖是否有益？如何有效控制餐后高血糖？如何有效控制餐后高血糖？餐后血糖控制目标及其监测餐后血糖控制目标及其监测STOP-NIDDM研究、MeRIA7荟萃分析是餐后血糖指南唯一引用的控制餐后血糖可获得心血管收益证据的临床研究Evidence Statements:Evidence Statements:Treatment with agents that target postmeal plasma Treatment with agents th

31、at target postmeal plasma glucose reduces vascular events.Level 1-glucose reduces vascular events.Level 1-Targeting both postmeal and fasting plasma glucose Targeting both postmeal and fasting plasma glucose is an important strategy for achieving optimal is an important strategy for achieving optima

32、l glycaemic control.Level 2+ glycaemic control.Level 2+ Recommendation: Implement treatment strategies to Recommendation: Implement treatment strategies to lower postmeal plasma glucose in people with lower postmeal plasma glucose in people with postmeal hyperglycaemia.postmeal hyperglycaemia.QUESTI

33、ON 2: Is treatment of postmeal hyperglycaemia beneficial?Agents which reduce day-long glycemia - Metformin, sulfonylureas, thiazolidinediones, premix, intermediate and long-acting insulinsAgents which preferentially improve postprandial hyperglycemia - -glucosidase inhibitors - Amylin analogs - Dipe

34、ptidyl peptidase-4 (DPP-4) inhibitors - Glinides - Glucagon-like peptide-1 (GLP-1) derivatives - Short- and rapid-acting insulinsPharmacologic TherapiesLong-term acarbose therapy reduces plasma glucose levelsYang W, et al. Chin J Endocrinol Metab 2001;17:1314.Change in plasma glucose level (mmol/L)C

35、ontrolDiet + exerciseAcarboseMetformin2-hour postchallenge plasma glucose*p0.001 vs control*Fasting plasma glucose1.51.00.500.51.0Chinese Prevention Study: Multicentre, 321 individuals, 3 yearsAcarbose is an effective combination therapy for type 2 diabetesInvestigatorPatients countryCombination the

36、rapyReduction in glycaemic measureHbA1c (%)1hPG (mmol/L)FPG(mmol/L)Lin1TW, PH, MY, KR, THAcarbose + SU1.0p=0.00182.6p=0.0020.8nsPhillips2AU, NZAcarbose + metformin1.0p=0.00011.1p=0.0395Sumual3IDAcarbose + metformin1.6p=0.01472.4p=0.02441.9p=0.0168Lam4CNAcarbose + various0.6p=0.0383.0p0.0010.7nsHwu5I

37、D, HK, TWAcarbose + insulin0.7p=0.0082.0p=0.0291.0ns1. Lin BJ, et al. J Diabetes Complic 2003;17:17985. 2. Phillips P, et al. Diabetes Care 2003;26:26973. 3. Sumual AR, et al. J Asian Fed Endocr Soc;2003;21:2431. 4. Lam KSL, et al. Diabetes Care 1998;21:115458.5. Hwu CM, et al. Diabetes Res Clin Pra

38、c 2003;60:11118.Risk markerPlaceboAcarboseBenefit of acarbose relative to placeboSerum CRP (mg/L)0.200.450.25p0.05Acarbose therapy improves cardiovascular risk markersWang XL, et al. EASD 2003 abstract 1634.Lu JM, et al. Chin J Endocrinol Metab 2003;19:2546.Change in CRP levels in individuals with p

39、rediabetesover 16 weeks (n=60)In the general population (n=154,NGT/prediabetes/diabetes),CRP levels correlated significantly with 2h-PG and HbA1c levelsAcarbose has a good safety profile in individuals with diabetes or prediabetes Acarbose has a non-systemic mode of action Most common AEs are mild-t

40、o-moderate gastrointestinal side-effects Lessen during initial weeks of therapy Reduced with start low, go slow stepwise dosing:50mg per day for 1 week 50mg b.i.d. for2 weeks 50mg t.i.d. thereafter1 Suitable for use in elderly patients1. Pan CY, et al. Diab Res Clin Pract 2003;61:18390.Acarbose has

41、excellent safety and efficacy profiles in ethnic Chinese type 2 diabetes patients in daily clinical practiceChina1 (n=2480)Taiwan2 (n=1558)FBG reduction (mg/dL)56.132.02h-PG reduction (mg/dL)111.352.2HbA1C reduction (%)1.91.0Very good/good efficacy (% of patients)90.146.0Very good/good tolerability

42、(% of patients)89.160.6Very good/good acceptance (% of patients)87.163.41. Su S-O, et al. Chin J Endocrinol Metab 2006;22:6a15.2. Hung Y-J, et al. Clin Drug Invest 2006;l26:55965. 拜唐苹通过降低餐后血糖，拜唐苹通过降低餐后血糖，显著降低显著降低HbA1c1.3%HbA1c1.3% 在最近的一项阿卡波糖与在最近的一项阿卡波糖与DDP-4DDP-4抑制剂的随抑制剂的随机、双盲、对照研究中（机、双盲、对照研究中（n=661

43、n=661），拜唐苹），拜唐苹使使HbA1c 1.3FPG 1.5mmol/L体重 1.7kgC. Pan, W. Yang*, DIABETIC Medicine, 1464-5491.2008QUESTION 3: Which therapies are effective in controlling postmeal plasma glucose?Evidence Statements: Diets with a low glycaemic load are beneficial in controlling postmeal plasma glucose.Level 1+ Sever

44、al pharmacologic agents preferentially lower postmeal plasma glucose.Level 1+ Recommendation: A variety of both non-pharmacologic and pharmacologic therapies should be considered to target postmeal plasma glucose.Agents which reduce day-long glycemia - Metformin, sulfonylureas, thiazolidinediones, p

45、remix, intermediate and long-acting insulinsAgents which preferentially improve postprandial hyperglycemia - -glucosidase inhibitors - Amylin analogs - Dipeptidyl peptidase-4 (DPP-4) inhibitors - Glinides - Glucagon-like peptide-1 (GLP-1) derivatives - Short- and rapid-acting insulinsPharmacologic T

46、herapiesConclusions from IDF Guidelines Regimens that target both fasting and postmeal glycaemia are needed to achieve optimal glucose control. However, optimal glycaemic control cannot be achieved without adequate management of postmeal plasma glucose. Therefore, treatment of fasting and postmeal h

47、yperglycaemia should be initiated simultaneously at any HbA1c level. Although cost will remain an important factor in determining appropriate treatments, controlling glycaemia is ultimately much less expensive than treating the complications of diabetes.Evidence StatementEvidence StatementPostmeal p

48、lasma glucose levels seldom rise above 7.8 mmol/l (140 mg/dl) in people with Postmeal plasma glucose levels seldom rise above 7.8 mmol/l (140 mg/dl) in people with normal glucose tolerance and typically return to basal levels two to three hours normal glucose tolerance and typically return to basal

49、levels two to three hours after food ingestion. Level 2+after food ingestion. Level 2+IDF and other organizations define normal glucose tolerance as 7.8 mmol/l (140 mg/dl) IDF and other organizations define normal glucose tolerance as 7.8 mmol/l (140 mg/dl) two hours following ingestion of a 75-g gl

50、ucose load. Level 4two hours following ingestion of a 75-g glucose load. Level 4The two-hour timeframe for measurement of plasma glucose concentrations is recommended The two-hour timeframe for measurement of plasma glucose concentrations is recommended because it conforms to guidelines published by

51、 most of the leading diabetes because it conforms to guidelines published by most of the leading diabetes organizations and medical associations. Level 4organizations and medical associations. Level 4Self-monitoring of blood glucose (SMBG) is currently the optimal method for assessing Self-monitorin

52、g of blood glucose (SMBG) is currently the optimal method for assessing plasma glucose levels. Level 1+plasma glucose levels. Level 1+It is generally recommended that people treated with insulin people perform SMBG at least It is generally recommended that people treated with insulin people perform

53、SMBG at least three times per day; SMBG frequency for people who are not treated with insulin three times per day; SMBG frequency for people who are not treated with insulin should be individualized to each persons treatment regimen and level of control should be individualized to each persons treat

54、ment regimen and level of control Level 4Level 4 Recommendations Recommendations Two-hour postmeal plasma glucose should not exceed 7.8 mmol/l (140 mg/dl) as long as Two-hour postmeal plasma glucose should not exceed 7.8 mmol/l (140 mg/dl) as long as hypoglycaemia is avoided.hypoglycaemia is avoided

55、.Self-monitoring of blood glucose (SMBG) should be considered because it is currently the Self-monitoring of blood glucose (SMBG) should be considered because it is currently the most practical method for monitoring postmeal glycaemia.most practical method for monitoring postmeal glycaemia.Efficacy

56、of treatment regimens should be monitored as frequently as needed to guide Efficacy of treatment regimens should be monitored as frequently as needed to guide therapy towards achieving postmeal plasma glucose target. therapy towards achieving postmeal plasma glucose target. QUESTION 4: What are the

57、targets for postmeal glycaemic control and how should they be assessed?Organisations recommendations for PPG targets1-2 h PP1-2 h PP10.0 mmol/L10.0 mmol/L180 mg/dL180 mg/dLADA 20065ADA 200652 h PP2 h PP 5.0-10.0 mmol/L 5.0-10.0 mmol/L90-180 mg/dL90-180 mg/dLCDA 20034CDA 20034UnspecifiedUnspecified4.

58、0-7.5 mmol/L4.0-7.5 mmol/L70-135 mg/dL70-135 mg/dLEuropean Cardiovascular European Cardiovascular Prevention Guidelines, Prevention Guidelines, 20043200432 h PP2 h PP8.0 mmol/L8.0 mmol/L140 mg/dL140 mg/dLAACE/ACE, 20052AACE/ACE, 200521-2 h PP1-2 h PP8.0 mmol/L8.0 mmol/L145 mg/dL145 mg/dLIDF 20051IDF

59、 20051TimingTimingPPG target valuesPPG target valuesOrganizationOrganizationPP = postprandialIDF Global guidelines 2005. GGT2D.pdf. AACE/ACE consensus statement. July 8, 2005.3. de Backer et al. Neurologia 2004;19:440450.4. CDA clinical practice guidelines. Can J Diabetes 2003; 27:S1S151.5. ADA clin

60、ical practice recommendations. Diabetes Care 2006; 29:S4S42. 目 录从ADA十年态度的转变到IDF餐后血糖指南颁布人类对PPG重要性的认识的进步拜唐苹作用于餐后血一糖而又超越餐后高血糖的新信息Acarbose therapy improves other metabolic risk factorsMetabolic risk factorPlaceboAcarboseBenefit of acarbose relative to placeboBody weight (kg)1.62.91.3p=0.0001Triglyceride level (