OSAHS与糖尿病疾病

ConfidentialJuly02,2012•阻塞性睡眠呼吸暂停•与糖尿病ConfidentialJuly02,2012糖尿病糖尿病分类•1型•2型•妊娠糖尿病•其它类型–病因•内分泌病•胰腺疾病•遗传等.糖尿病的主要类型占95%+ConfidentialJuly02,20122型糖尿病•最常见的糖尿病•占糖尿病的85-90%•临床危险因素:–肥胖–年龄–高血压–家族史–心脏病或心脏病发作史–吸烟–高胆固醇–代谢调控低下–睡眠呼吸紊乱ConfidentialJuly02,20122型糖尿病的发生与发展•2型糖尿病不是短期内速发的，是多年不良生活方式不良积累的结果•2型糖尿病发生过程中，要度过数个糖尿病前期（pre-diabetesstages）:–葡萄糖耐量损害(IGT)•OGTT2小时后，7.8血浆葡萄糖11.1mmol/L–空腹血糖改变(IFG)•6.1空腹血糖7mmol/LConfidentialJuly02,2012糖尿病的公共卫生问题•估计影响到全球人口的5-7%，为严重的全球健康问题。•预计患病人数从2006年2.3亿将增加到2025年3.5亿。•糖尿病患者的总体寿命约会减少25%•糖尿病患者死亡的主要原因:–心血管疾病–脑血管疾病–神经病变–糖尿病昏迷–感染ConfidentialJuly02,2012澳大利亚糖尿病发病率Busselton1981250,0001983400,0001990550,0001995725,00020001,000,000AUSDIABDunstanDetalDiabetesCare2002ConfidentialJuly02,2012糖尿病的发病率趋势(%):1981-20001.31.71.44.67.515.30.36.213.118.62.523.605101520253025-3435-4445-5455-6465-7475+Agegroup(years)%1981Busselton2000AusDiabConfidentialJuly02,2012美国糖尿病的发病趋势ConfidentialJuly02,2012亚太地区糖尿病的发病趋势ConfidentialJuly02,2012日本儿童的2型糖尿病发病趋势ConfidentialJuly02,2012不幸的是，它还在继续发展ConfidentialJuly02,2012并存疾病高血压•发生率较普通人群高2倍–10-30%的1型糖尿病患者–30-50%的2型糖尿病患者•控制糖尿病患者的高血压非常重要，因为后者可加重糖尿病的血管并发症。•糖尿病患者并存高血压使冠心病发生的危险性增高了2-5倍。•高血压加重了糖尿病对左心室及其功能的损害。ConfidentialJuly02,2012并存疾病心血管疾病•与普通人群相比，糖尿病患者的心脏病、脑卒中和外周血管疾病的发生率要高出约2-4倍。•CVD是2型糖尿病I患者最主要的死亡原因(75%)。微血管病变•视网膜病变•肾病•神经病变ConfidentialJuly02,2012OSA与2型糖尿病Type2DiabetesObesityAgeSmokingPhysicalInactivitySDBSleep-disorderedBreathingObesityNecksizeAgeSmokingPhysicalInactivityDiabetesConfidentialJuly02,2012流行病学调查•每晚睡眠时间不足7小时者BMI更高(USNationalHealthandNutritionExaminationsurvey).•睡眠剥夺约多，体重增长越重(USNursesHealthStudy)•每晚睡眠7.7小时者BMI的预计值最低。(WisconsinSleepCohortStudy)•儿童晚间少睡眠1小时，发生肥胖的危险性增高80%。ConfidentialJuly02,2012睡眠剥夺对激素分泌的影响Spiegel,K.JClinEndo&Met:89(11)5762-5771;2004LeptinCortisolHOMA(IR)ConfidentialJuly02,2012OSA与胰岛素抵抗1985Guilleminaultfound5/12DM2patientshadSDB1988Japanesestudyfound11/28SDBpatientshadDM21996Numerouscontradictoryreportsofassociation“casual,intriguing,andhighlyspeculative”KPStrohl1998OSApostulatedasamanifestationofthemetabolicsyndrome(SyndromeZ=SyndromeX+OSA)obesity,hypertension,hyperlipidemia,insulinresistanceandOSA2002-03NumerousreportslinkOSAtoinsulinresistanceindependentofotherfactors2005WisconsinSleepCohortfindsindependentassociationbetweendiabetesandOSAConfidentialJuly02,20122型糖尿病与OSA相关性的研究YearLocationNProtocolandresult1984-94UppsalaUniversity(2000)2668(30–69yrs)Sleep&metabolicdiseasequestionnaireDevelopedDM2:Nonsnorers2.4%;Snorers5.4%Obesenon-snorers:8.6%;obesesnorers13.5%1986-96NursesHealthStudyHarvardUni(2002)69852(f)(40-65yrs)1957developedDM2.Byquestionnaire:OccasionalsnoringvsnonsnoringRR=1.48Regularsnoringvsnonsnoring=2.25IndeptofBMI,smoking,parentalhistory1994-99Sleephearthealthstudy(2004)2656Glucoseintoleranceby2hrglucosemeasurementRDI5,referenceRDI5-15,OR=1.27,RDI15,OR=1.46Independentage,gender,BMI,waistcircumference4yrfollow-upWisconsinsleepcohort(2005)1387Diabetes;AHI5,2.8%;AHI15,15%;OR=2.3ORfordevelopingDM2in4yrs=1.62Indeptofage,sex,bodyhabitusConfidentialJuly02,20122型糖尿病与OSA并存的发病率•普通人群的OSA预计发病率5%.•普通人群的2型糖尿病预计发病率7%.•OSA患者中2型糖尿病预计发生率为20%(ReichmuthAJRCCM2005)and30%(MeslierEurRespJ2003).•患者中2型糖尿病患者中OSA预计发生率高达58%(Resnick(DiabetesCare2003))•男性中2型糖尿病与OSA和年龄显著相关.•45yrs:11%,•between45and60years:36%,•65yearswas61%.•Correspondingnumbersforwomen:0%,21%and8%respectively.ConfidentialJuly02,2012OSA与2型糖尿病相关的原因OSA与以下因素相关1.交感神经张力增高，血、尿儿茶酚胺增加糖原分解和糖异生增强血糖稳态受影响2.与胰岛素抵抗和2型糖尿病发病相关的炎症细胞因子如IL-6,TNF-,andC-反应蛋白增高3.血管内皮功能紊乱，有胰岛素抵抗的OSA患者心钠素(ANP)及内皮素－１水平增高。4.OSA与脂肪组织因子(leptinandadiponectin)水平异常相关，后者对调节血糖稳态的生理过程具有广泛的外周效应。ConfidentialJuly02,2012OSA、胰岛素抵抗和2型糖尿病的相关机理(Punjabietal,JApplPhysiol,Vol99,Nov2005)ConfidentialJuly02,2012OSA患者交感神经张力增高Narkiewiczetal1998CirculationConfidentialJuly02,2012OSA患者血管内皮功能紊乱Ipetal2004AJRCCMConfidentialJuly02,2012OSA患者炎症因子水平增高Minoguchietal2005AJRCCM血清IL-18水平在肥胖对照组(n=16),轻度OSA组(n=13),和中、重度OSA组(n=23)ConfidentialJuly02,2012近期的研究•OSA与胰岛素抵抗和2型糖尿病独立相关。(Punjabi(JAP2005),Coughlin(EurheartJ2004),Reichmuth((AMJRCCM2005)).•胰岛素抵抗随OSA的严重程度增高而增强。(Ip(AMJRCCM2002),Punjabi(AMJRCCM2002)).ConfidentialJuly02,2012OSA对葡萄糖调控的影响研究提示对有OSA的2型糖尿病患者行有效的CPAP治疗可显著改善机体对葡萄糖的调控机能。(Harsch,AJRCCM2004,BabuArchInternMed2005).ConfidentialJuly02,201221.IAHarschDepartmentofMedicineI,Friedrich-AlexanderUniversityErlangenNuremburg,Erlangen,Germany.AmJRespirCritCareMed.2004;169(2):156-162CPAP治疗改善胰岛素的敏感性Showsimprovementofinsulinsensitivityindex(ISI)atbaseline,2daysand3monthsafteronsetofCPAPtreatmentin31patentsWithin48hours,significantimprovementshavebeendemonstratedinInsulinSensitivityusingCPAPtherapy21ConfidentialJuly02,2012CPAP治疗3月对空腹和餐后血糖的影响024681012012345Glucose(mmol/l)FastingB’fastLunchDinnerBabuetal.ArchInternMed.2005;165:447-521hrpost-prandial**P0.05beforevsafterBaseline3mthCPAPConfidentialJuly02,20127.07.58.08.59.09.5AllpatientsHbA1c7%HbA1c(%)BeforeCPAPAfterCPAPBabuetal.ArchInternMed.2005;165:447-52P=0.06P=0.02CPAP治疗3月对HbA1c的影响ConfidentialJuly02,2012HbA1c的改善与CPAP的每晚使用时间相关Babuetal.ArchInternMed.2005;165:447-52CPAPuse4h/dayCPAPuse4h/dayConfidentialJuly02,2012使用AlicePDx便携式监测设备筛查2型糖尿病患者的OSA