2022年医学专题—潘长玉2型糖尿病血糖控制的意义及实践(1).ppt

2型糖尿病血糖控制(kngzh)的意义及实践解放军总医院 潘长玉2003年03月15日,第一页，共三十四页。,糖尿病治疗学上的重大(zhngd)问题,血糖控制与并发症上世纪20年代初胰岛素问世，欢呼糖尿病治疗已彻底解决4050年代经胰岛素治疗的患者2030年后出现多种糖尿病并发症心血管、肾脏、神经、视网膜并发症的防治提上议事日程加强血糖控制能否降低并发症发生率意见矛盾哈佛学派(含Joslin Clinic)支持严格控制血糖预防并发症，耶鲁学派认为血糖控制与并发症无关，双方皆同意需作前瞻性研究(ynji)澄清这一问题,第二页，共三十四页。,美国大学组糖尿病计划(jhu)(UGDP),目的：澄清“严格”控制(kngzh)或“较松”控制(kngzh)血糖对糖尿病并发症的影响多中心、12所大学、长程、前瞻性、随机、双盲、安慰剂对照试验1958年开始，历时14年1027例NIDDM随机分为5组，每组约200例 甲苯磺丁脲1.5克/天 苯乙双胍100 mg/天 固定剂量胰岛素(按体表面积)调节胰岛素剂量控制血糖接近正常安慰剂患者皆接受饮食控制,第三页，共三十四页。,UGDP主要(zhyo)结果,甲苯磺丁脲组因猝死率较高，估计为心血管原因，提前停止苯乙双胍组晚18个月开始，亦因不良反应较安慰剂组高而提前中止安慰剂、固定胰岛素、按需胰岛素3组相比UGDP未能证实较好的血糖控制可预防或延缓(ynhun)并发症的发生,第四页，共三十四页。,UGDP 607例患者不按随机分组而按血糖控制程度分析，所显示的致命(zhmng)及非致命(zhmng)事件发生率,血糖控制 好(183例)尚可(239例)差(185例)视网膜病变(渗出)38.548.257.3血清肌酐1.5 mg/dl11.614.014.4高血压(WHO)标准52.371.375.4心血管死亡 占死亡数%27.432.140.5 占总数(zngsh)%12.611.318.3结论：血糖控制差者并发症及心血管死亡率皆较高,第五页，共三十四页。,高血糖毒性(d xn)作用仍要受到重视,糖尿病干预治疗及并发症的流行病学研究(ynji)（EDIC 19942006)受试者 DCCT两组情况（6年）2000年 原常规组 原强化组HbA1c 8.1%8.2%IMT 10%7.6%,第六页，共三十四页。,UKPDS血糖试验主要(zhyo)RCT结果,终点(事件数)RR下降 p 值任何糖尿病相关终点(1401)12%0.029微血管病变(bngbin)(346)25%0.0099糖尿病相关死亡(414)10%0.34所有原因死亡(702)6%0.44心肌梗死(573)16%0.052卒中(203)+11%0.52周围血管病变(47)35%0.15(下肢截肢或致命性病变)心衰(116)9%0.63,第七页，共三十四页。,UKPDS血糖与并发症观察(gunch)性研究,目的：不同层次血糖控制与并发症的关系了解微血管病变及心血管病变出现是否有阈值纳入3642例患者作事件相对(xingdu)危险性研究由每例患者年HbA1c测定均值算出逐年HbA1c总平均值每例按HbA1c总平均值进行分层，各层中位数如下(%):5.6，6.5，7.5，8.4，9.4此研究中含6%空腹血糖(调节)减退者(血糖110125 mg/dl)事件发生率计算法：发生某一并发症例数除以随访的人年数，以事件数/1000人年计算上述计算事件发生率按性别、种族、糖尿病诊断时年龄、糖尿病病程加以校正按基线血压、血脂、吸烟等因子校正后，仍然有效,第八页，共三十四页。,第九页，共三十四页。,UKPDS血糖与并发症观察(gunch)性研究结论,2型糖尿病患者，糖尿病并发症的危险与患者的高血糖明显相关与HbA1c正常者(6%)相比，血糖愈高并发症发生率愈高不存在明显的发生并发症的血糖阈值提示降低血糖可降低并发症发生率微血管病变与血糖升高的关系(gun x)更为密切大血管病变与血糖升高也有关，但还有其他致病因素，血糖亦起重要作用卒中及心衰发生率与高血糖有关，但与高血压关系更密切,第十页，共三十四页。,2型糖尿病的药物(yow)冶疗,增加(zngji)胰岛素的可用牲Sulfonylurease.g.Glipizide/Glipizide XL,Glyburide,GlimepirideMeglitinides(very short acting)Repaglinide,NateglinideInsulin增加葡萄糖的吸收-glucosidase inhibitorsAcarboseMiglitol,减少(jinsho)肝糖输出 Metformin胰岛素增敏剂ThiazolidinedionesPioglitazoneRosiglitazone减肥药Reduce Fat AbsorptionOrlistatReduce AppetiteSibutraminePhentermine,第十一页，共三十四页。,磺脲类药物,特征(tzhng)long-acting insulin secretagoguesrapid benefitsome potential differences among agents指征monotherapycomb with TZD or metformincomb with insulin,优点(yudin)50 years of experiencegood efficacyvery effective in combination therapyproven microvascular outcomes inexpensive不足cause hypoglycemiamodest weight gaincardiovascular benefits to be proven,第十二页，共三十四页。,短效促胰岛素分泌(fnm)剂,特征(tzhng)long Nateglinide is a D-phenylalanine deriv.Repaglinide is a meglitinide Rapid onset/short dur.Pimarily affect ppg指征monotherapycomb.with metformin,Potential优点(yudin)possibly less hypoglycemia and less weight gain than SUs e.g missed meals;nightOK in renal failuretargets postprandial不足expensiverequire more dosesNateglinide is less effective than SU or repaglinide,第十三页，共三十四页。,Metformin,特征(tzhng)longPrimary mechanism is reduction of hepatic glucose productionImproved insulin sensitivity in livermoderately rapid affect指征monotherapycomb with TZD or secretagogue comb with insulin,优点(yudin)long experiencegood efficacyweight benefitsproven microvascular&macrovascular outcomes moderate cost不足GI side effectsmany contraindicationslactic acidosis,第十四页，共三十四页。,噻唑(sizu)烷二酮类,特征(tzhng)longtrue skeletal muscle sensitizersreduce FFAeffective once dailyrelatively slow onset 指征monotherapycomb with SU or Metcomb with insulin*,优点(yudin)very effective in highly insulin resistant pts.OK in renal diseasepossible cv benefit(?)-cell protective(?)不足expensiveweight gainedemacan induce CHF,*rosiglitazone not approved for this use,第十五页，共三十四页。,2型糖尿病的联合(linh)用药,There exist four classes of pharmacologic agents Combining agents from different classes provides at least additive benefits without additive toxicityPotential Indications:improve glucose control when maximally effective dose of a single agent has failed to keep the HbA1C 7.0%avoid adverse effects that occur with high doses of single agentlimit insulin dose in highly resistant patients(e.g.1u/kg/d)Long-term and comparative benefits of various combinations have not been studied,第十六页，共三十四页。,口服药治疗(zhlio)失效加用睡前胰岛素,Continue the two oral agents may reduce SU to 1/2 max doseAdd Glargine or NPH at bedtime or 70/30 or Humalog Mix 75/25 before dinnerbegin with 0.15 u/kg;dose by 4-6 u q 3-5 days until fasting BG is 120;then more slowly to 100 mg/dlIf evening insulin s FBS to 100 but acD is go to multiple daily injections or premixedIf FBS and acD are ok but HS is high 70/30 acD or give short-acting at dinnerReduce one of the two oral agents if BGs 120,第十七页，共三十四页。,夜间(y jin)胰岛素的作用,Reduce nocturnal hepatic glucose production(fights“dawn phenomenon”)Requires lower insulin levels than those required for stimulating intramuscular glucose uptakeReduces glucotoxicityelevated glucose levels create insulin resistanceelevated glucose levels reduce beta cell response,第十八页，共三十四页。,口服药与胰岛素联合(linh)应用,Any combination may reduce insulin dosethis may not always be of great benefit or be cost effectiv