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Eur Heart:肥胖和达格列净对2型糖尿病患者心血管和肾脏结局的影响

2021-11-10 从医路漫漫 MedSci原创

肥胖和2型糖尿病(T2DM)的发病率和患病率不断上升,是当今全球公共健康面临的最具挑战性的威胁之一。

背景:肥胖和2型糖尿病(T2DM)的发病率和患病率不断上升,是当今全球公共健康面临的最具挑战性的威胁之一。肥胖在T2DM的发生发展中起着至关重要的作用,而T2DM又与冠心病(CAD)、心力衰竭(HF)、脑卒中、其他心血管疾病(CV)和糖尿病肾病的风险密切独立相关。肥胖也是HF、CAD、房颤(AF)和肾脏疾病发展的独立危险因素,部分原因是它影响高血压、血脂异常、血糖不耐受或糖尿病等并发症的发展和严重程度。但是有许多研究提出了一个肥胖的相反结论,即体重指数(BMI)、身体脂肪百分比或中心型肥胖定义的超重或中度肥胖,与体重不足、正常或严重肥胖的人相比,死亡率较低。然而,在钠-葡萄糖共转运体2抑制剂(SGLT2i)治疗的患者中,关于肥胖与CV结局和药物治疗效果之间的资料很少。

方法:DECLARE–TIMI 58试验中,使用达格列净与安慰剂对T2DM和动脉粥样硬化心血管(CV)疾病或多种危险因素患者进行随机化治疗。患者按体重指数(BMI, kg/m2)进行分层:正常(18.5 ~ <25)、超重(25 ~ <30)、中度肥胖(30 ~ <35)、严重肥胖(35 ~ <40)和非常严重肥胖(>_40)。

该试验有两个主要治疗终点:心血管病死亡或HHF和主要心血管不良事件(MACE)的复合(心血管病死亡、心肌梗死或缺血性卒中的复合)。还评估了CV死亡/HHF和MACE的部分,肾功能特异性的综合结局[估计肾小球滤过率(eGFR)持续下降≥40%,终末期肾病,或肾死亡],AF或心房扑动(AFL)。在筛查期、基线、6个月、12个月和之后每年测量血肌酐。在试验结束时,或在最后一次治疗来访时,对过早停用研究药物的患者进行血清肌酐测定。心房颤动/AFL事件是通过搜索安全数据库中的不良事件确定的。结果分析包括心血管死亡、心衰住院(HHF)、肾脏特异性复合结局和心房颤动或扑动(AF/AFL)。

结果:17134例患者中BMI正常者为9.0%,超重者为31.5%,中度肥胖者为32.4%,重度肥胖者为17.2%,极重度肥胖者为9.8%。较高的BMI与HHF和AF/AFL的调整风险较高相关(风险比分别为1.30和1.28,每5kg/m2;P均< 0.001)。达格列净降低体重的相对值在BMI分组中一致(百分比差异:-1.9至-2.4%)。虽然达格列净在CV和肾脏特异性复合结局中的相对风险降低在BMI范围内没有显著差异(交互作用的p值≥ 0.20),但肥胖患者(BMI≥30 kg/m2)在HHF和AF/AFL中的绝对风险降低更多(交互作用p值分别为0.02和0.09)。

图1 安慰剂组按体重指数分类分层的临床结果。以正常体重指数分类作为参考。AF/AFL,心房颤动或心房扑动;CI,置信区间;CV,心血管;HHF,心力衰竭住院;HR,危险比;Km,Kaplan-Meier。

图2 按体重指数分类的随机治疗组的平均体重随时间变化百分比:A为正常;在B超重;C组中度肥胖;D组严重肥胖;E. CI,置信区间是非常严重的肥胖。*平均百分比差异按治疗组间平均最小二乘平均百分比差异计算。

图3 按体重指数计算的达格列净对临床结果的影响,A为心血管死亡/心力衰竭住院,B为心力衰竭住院,C为肾脏特异性综合结局,D为房颤或心房扑动,房颤/房颤或心房扑动;CV,心血管;HHF,心力衰竭住院。

结论:在DECLARE-TIMI58中,T2 DM和BMI较高的患者更有可能发生HHF和AF/AFL。虽然达格列在心血管和肾脏结局方面降低的相对风险在BMI范围内基本一致,但在肥胖T2DM患者中,HHF和AF/AFL等肥胖相关结局的绝对风险降低更多。

原文出处:

Oyama K,  Raz I,  Cahn A,et al.Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE-TIMI 58 trial.Eur Heart J 2021 Aug 24

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  5. [GetPortalCommentsPageByObjectIdResponse(id=1357824, encodeId=5119135e82450, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1383733, encodeId=29b11383e33e8, content=<a href='/topic/show?id=196a1101f7' target=_blank style='color:#2F92EE;'>#2型糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1101, encryptionId=196a1101f7, topicName=2型糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec19483, createdName=aids213, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1428699, encodeId=7fac1428699ad, content=<a href='/topic/show?id=71b182e3237' target=_blank style='color:#2F92EE;'>#肾脏结局#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82732, encryptionId=71b182e3237, topicName=肾脏结局)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=76614125796, createdName=szhvet, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1475165, encodeId=c00714e516572, content=<a href='/topic/show?id=935fe6718e3' target=_blank style='color:#2F92EE;'>#糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76718, encryptionId=935fe6718e3, topicName=糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a38f7243741, createdName=xue8604, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1563544, encodeId=93ec156354424, content=<a href='/topic/show?id=f69d864413' target=_blank style='color:#2F92EE;'>#HEART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8644, encryptionId=f69d864413, topicName=HEART)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=80d715270048, createdName=slcumt, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1068947, encodeId=5cb1106894e27, content=学习了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fd8b5623723, createdName=ms6000000656440728, createdTime=Wed Nov 10 13:24:02 CST 2021, time=2021-11-10, status=1, ipAttribution=)]
    2021-11-11 slcumt
  6. [GetPortalCommentsPageByObjectIdResponse(id=1357824, encodeId=5119135e82450, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1383733, encodeId=29b11383e33e8, content=<a href='/topic/show?id=196a1101f7' target=_blank style='color:#2F92EE;'>#2型糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1101, encryptionId=196a1101f7, topicName=2型糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec19483, createdName=aids213, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1428699, encodeId=7fac1428699ad, content=<a href='/topic/show?id=71b182e3237' target=_blank style='color:#2F92EE;'>#肾脏结局#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82732, encryptionId=71b182e3237, topicName=肾脏结局)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=76614125796, createdName=szhvet, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1475165, encodeId=c00714e516572, content=<a href='/topic/show?id=935fe6718e3' target=_blank style='color:#2F92EE;'>#糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76718, encryptionId=935fe6718e3, topicName=糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a38f7243741, createdName=xue8604, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1563544, encodeId=93ec156354424, content=<a href='/topic/show?id=f69d864413' target=_blank style='color:#2F92EE;'>#HEART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8644, encryptionId=f69d864413, topicName=HEART)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=80d715270048, createdName=slcumt, createdTime=Thu Nov 11 12:28:02 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1068947, encodeId=5cb1106894e27, content=学习了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fd8b5623723, createdName=ms6000000656440728, createdTime=Wed Nov 10 13:24:02 CST 2021, time=2021-11-10, status=1, ipAttribution=)]
    2021-11-10 ms6000000656440728

    学习了!

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