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Diabetes:恩格列净治疗通过减小心肌细胞体积改善2型糖尿病患者心脏能量和功能

2021-11-04 从医路漫漫 MedSci原创

心血管疾病是2型糖尿病患者发病率和死亡率的主要原因。心力衰竭(HF)是T2D中最常见的心血管疾病的首发表现。

心血管疾病是2型糖尿病患者发病率和死亡率的主要原因。心力衰竭(HF)是T2D中最常见的心血管疾病的首发表现钠-葡萄糖-共转运蛋白-2(SGLT2)抑制剂与患有或高危心血管疾病的T2D患者心力衰竭住院风险较低相关。在EMPA-REG结果试验中,选择性SGLT2抑制剂恩格列净使心血管病死率和因心力衰竭住院时间分别减少38%和35%。SGLT2抑制剂是独特的口服降糖治疗方案,除了改善血糖控制外,SGLT2抑制剂还被批准用于降低T2D和既往心血管疾病患者的心血管疾病和死亡率的风险。HF在SGLT2抑制剂治疗后变化最明显,这一理论随后也在卡格列净和达格列净试验中得到证实。因此认为SGLT2抑制剂可降低2型糖尿病(T2D)患者主要不良心血管事件和心力衰竭住院的风险。

方法:在一项纵向队列研究中,在T2D患者治疗前和治疗间隔12周的两次访问和对照组的一次访问。对照组没有接受恩格列净治疗。记录身高和体重,计算体重指数(BMI),血压(BP)记录为10分钟内平均3次仰卧位血压,并在31P-MRS和CMR扫描前记录两次静息心电图,并从心电图中记录静息心率。在两次访问中,每个参与者都抽取空腹血进行全血计数、估计肾小球滤过率(EGFR)、胰岛素、甘油三酯、肝功能、糖化血红蛋白(HbA1c)、N-末端前激素B型利钠肽(NT-proBNP)水平的评估。

所有扫描均在3.0特斯拉磁共振系统上进行。所有参与者都在第一次扫描和第二次扫描之间几乎同一时间进行了扫描。31P发射器/接收器心脏线圈放置在他们的心脏位置上,位于磁铁的等中心。线圈位置标准化,置于室中隔上方。31P-MRS数据采集采用非门控三维采集加权化学位移成像(CSI)序列。该协议的采集矩阵为16x8x8。视野为240x240x200 mm。31P-MRS研究之后,在相同的研究访问中,在更换线圈后使用相同的扫描仪进行CMR。研究人员建议参与者在研究前24小时内避免摄入咖啡因。在31P-MRS之后,CMR方案包括使用稳态自由进动(SSFP)序列的电影成像、自然和增强后T1映射、应力和静息灌注以及晚期钆增强(LGE)。晚期钆增强(LGE)成像使用相敏反转恢复(PSIR)序列在匹配的LV短轴平面和长轴平面上进行,以排除既往心肌梗死或区域性纤维化的存在(在造影剂注射后>8分钟)。

因此,利用心血管磁共振成像(CMR)和31磷磁共振波谱(31P-MRS),探讨选择性的SGLT2i 恩格列净对心肌能量学、细胞体积、功能和灌注的影响。共纳入18例T2D患者在恩格列净治疗12周前后分别行CMR和31P-MRS扫描。测定血浆N端激素前B型利钠肽(NT-proBNP)水平。10名血糖控制正常的志愿者进行相同的扫描方案。

结果:恩格列净治疗显著改善了PCr/ATP比值(1.52 ~ 1.76,p=0.009)。与基线测量值相比,LVEF绝对值平均增加7% (p=0.001),总体纵向应变绝对值平均增加3% (p=0.01),心肌细胞体积绝对值平均减少8 ml/m2 (p=0.04), NT-proBNP相对减少61% (p=0.05)。心肌血流和舒张应变无明显变化。

表1 恩格列净治疗后临床参数的变化

表2 恩格列净治疗后CMR结果的变化

图1 2型糖尿病患者与对照组基线时心肌磷酸肌酸与ATP比值(PCr/ATP)的比较以及恩格列净治疗12周前后PCr/ATP的变化。

图2 比较基础状态下2型糖尿病患者和对照组的左心室射血分数(LVEF),以及治疗12周前后左心室射血分数(LVEF)的变化。

结论:恩格列净改善了“心脏能量不足”状态,逆转了不利的心肌细胞重构,并改善了心脏功能,为T2D中预防或治疗心衰提供了治疗机会

原文出处:

Thirunavukarasu S,  Jex N,  Chowdhary A,et al.Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes.Diabetes 2021 Oct 05

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    2021-11-05 ms1000001920226686

    xuexi

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  6. [GetPortalCommentsPageByObjectIdResponse(id=1902656, encodeId=0b181902656cf, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5917, encryptionId=c097591ed5, topicName=Diabetes)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0045169, createdName=木头人513, createdTime=Wed Mar 02 05:59:31 CST 2022, time=2022-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761737, encodeId=f0f81e6173773, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Fri Mar 04 06:59:31 CST 2022, time=2022-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639933, encodeId=8673163993397, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Wed Sep 21 04:59:31 CST 2022, time=2022-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067262, encodeId=4c13106e262ce, content=xuexi, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=70c25441341, createdName=ms1000001920226686, createdTime=Fri Nov 05 12:25:10 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1383729, encodeId=82b21383e29dc, 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=75, 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=Fri Nov 05 09:59:31 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1475159, encodeId=835a14e5159a3, 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=67, 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=Fri Nov 05 09:59:31 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066964, encodeId=e89e106696483, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=0fb85496390, createdName=zyh147258, createdTime=Thu Nov 04 15:49:36 CST 2021, time=2021-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066961, encodeId=7e181066961f3, content=降低血糖的同时有心血管的获益,确实不错。, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e39e5226547, createdName=1478fcfem77暂无昵称, createdTime=Thu Nov 04 15:43:11 CST 2021, time=2021-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066958, encodeId=9a6b1066958b2, content=学习了!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e39e5226547, createdName=1478fcfem77暂无昵称, createdTime=Thu Nov 04 15:39:46 CST 2021, time=2021-11-04, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1902656, encodeId=0b181902656cf, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5917, encryptionId=c097591ed5, topicName=Diabetes)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0045169, createdName=木头人513, createdTime=Wed Mar 02 05:59:31 CST 2022, time=2022-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761737, encodeId=f0f81e6173773, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Fri Mar 04 06:59:31 CST 2022, time=2022-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639933, encodeId=8673163993397, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Wed Sep 21 04:59:31 CST 2022, time=2022-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067262, encodeId=4c13106e262ce, content=xuexi, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=70c25441341, createdName=ms1000001920226686, createdTime=Fri Nov 05 12:25:10 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1383729, encodeId=82b21383e29dc, 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=75, 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=Fri Nov 05 09:59:31 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1475159, encodeId=835a14e5159a3, 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=67, 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=Fri Nov 05 09:59:31 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066964, encodeId=e89e106696483, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=0fb85496390, createdName=zyh147258, createdTime=Thu Nov 04 15:49:36 CST 2021, time=2021-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066961, encodeId=7e181066961f3, content=降低血糖的同时有心血管的获益,确实不错。, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e39e5226547, createdName=1478fcfem77暂无昵称, createdTime=Thu Nov 04 15:43:11 CST 2021, time=2021-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066958, encodeId=9a6b1066958b2, content=学习了!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e39e5226547, createdName=1478fcfem77暂无昵称, createdTime=Thu Nov 04 15:39:46 CST 2021, time=2021-11-04, status=1, ipAttribution=)]
    2021-11-04 zyh147258

    学习了

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1902656, encodeId=0b181902656cf, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5917, encryptionId=c097591ed5, topicName=Diabetes)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0045169, createdName=木头人513, createdTime=Wed Mar 02 05:59:31 CST 2022, time=2022-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761737, encodeId=f0f81e6173773, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Fri Mar 04 06:59:31 CST 2022, time=2022-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639933, encodeId=8673163993397, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Wed Sep 21 04:59:31 CST 2022, time=2022-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067262, encodeId=4c13106e262ce, content=xuexi, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=70c25441341, createdName=ms1000001920226686, createdTime=Fri Nov 05 12:25:10 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1383729, encodeId=82b21383e29dc, 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=75, 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=Fri Nov 05 09:59:31 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1475159, encodeId=835a14e5159a3, 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=67, 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=Fri Nov 05 09:59:31 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066964, encodeId=e89e106696483, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=0fb85496390, createdName=zyh147258, createdTime=Thu Nov 04 15:49:36 CST 2021, time=2021-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066961, encodeId=7e181066961f3, content=降低血糖的同时有心血管的获益,确实不错。, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e39e5226547, createdName=1478fcfem77暂无昵称, createdTime=Thu Nov 04 15:43:11 CST 2021, time=2021-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066958, encodeId=9a6b1066958b2, content=学习了!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e39e5226547, createdName=1478fcfem77暂无昵称, createdTime=Thu Nov 04 15:39:46 CST 2021, time=2021-11-04, status=1, ipAttribution=)]
    2021-11-04 1478fcfem77暂无昵称

    降低血糖的同时有心血管的获益,确实不错。

    0

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    2021-11-04 1478fcfem77暂无昵称

    学习了!!!

    0

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