Diabetes Obes Metab：每日三次的基础胰岛素治疗中加入短效艾塞那肽对1型糖尿病患者骨代谢的影响

2021-11-10 从医路漫漫 MedSci原创

与健康人相比，1型糖尿病患者骨折风险增加3倍，其中髋部骨折风险增加近4倍，死亡率也随之增加。而风险可能取决于血糖控制，独立年龄和性别。1型糖尿病髋部骨折风险增加的部分原因是骨密度降低。

背景：与健康人相比，1型糖尿病患者骨折风险增加3倍，其中髋部骨折风险增加近4倍，死亡率也随之增加。而风险可能取决于血糖控制，独立年龄和性别。1型糖尿病髋部骨折风险增加的部分原因是骨密度降低。骨矿物质含量减低和胶原蛋白弹性强度受损导致骨强度降低，以及骨质缺失和骨重塑减少可能也是原因之一。在骨重塑减少方面，与健康对照组相比，糖尿病患者的骨吸收标志物、I型胶原C端肽(CTX)以及骨形成标志物、I型胶原氨基端前肽(P1NP)均出现下降。有趣的是，肠促胰岛素激素如胰高血糖素样肽-1 (GLP-1)似乎与骨组织相互作用。这种相互作用的机制研究很少，但是已观察到外源性GLP-1影响CTX的血浆水平。

目的:评价短效胰高血糖素样肽-1受体激动剂艾塞那肽加入胰岛素治疗后对1型糖尿病骨密度和骨代谢指标的影响。

材料与方法：MAG1C试验是一项为期26周的随机、双盲、安慰剂对照临床试验，对108例接受基础胰岛素治疗的年龄在18岁以上、体重指数>22kg/m²、HbA1c为59-88 mmol/mol (7.5%-10.0%)的1型糖尿病患者随机(1：1)在早餐、午餐和晚餐前给予10μg艾塞那肽(Byetta)，作为胰岛素治疗的补充治疗，共持续26周。排除标准包括胰岛素泵治疗、无意识低血糖、糖尿病胃轻瘫、肾功能受损和增殖性视网膜病变。

计划在第0周(随机分组)、第4周、第12周和第26周(治疗结束)进行4次随访，就诊前一晚10:00开始禁食。使用Hologic Discovery QDR系列82800 Apex 3.3扫描仪(Hologic Canada ULC, Mississauga, Canada)在第0周和第26周通过全身、臀部、腰椎和前臂DXA扫描测量骨成分。所有访视者均采集空腹血样，以80℃保存在生物样本库。研究结束后，使用IDS-iSYS多学科自动化系统(immunodiagnostics System, Frankfurt am Main, Germany)的自动化学发光免疫分析法分析血浆CTX和P1NP水平。

结果:与安慰剂相比，艾塞那肽减轻了4.4 kg的体重，但在治疗26周后，通过全身、髋关节、腰椎和前臂双能x线骨密度测量，观察到两组之间的骨密度没有差异。26周后，艾塞那肽与安慰剂相比，I型胶原的c端肽(骨吸收的标记物)和I型胶原的氨基端前肽(骨形成的标记物)的空腹血浆水平没有变化。

表1 用双能x线骨密度仪测量的骨密度

表2 骨转换的生物标志物

图在1型糖尿病患者中，与安慰剂相比，每天使用三次短效埃塞那肽对骨吸收(CTX评估)和骨形成(P1NP评估)的影响。A、每周CTX中位数的变化。B、P1NP中位数周变化。值是来自线性混合模型的具有95%置信区间的中值，该线性混合模型结合了基线调整来处理意向治疗总体中具有最大似然估计(等于多重补偿)的缺失数据。环磷酰胺正常范围：男性平均0.294(95%CI 0.115~0.748)ng/mL，绝经前女性平均0.287(0.112~0.738)ng/mL，绝经后女性0.439(0.142~1.351)ng/mL，P1NP正常范围27.7~1.351 ng/mL。CI，可信区间；CTX，I型胶原C端肽；ETD，估计治疗差异；P1NP，I型前胶原氨基端前肽

结论:尽管艾塞那肽诱导体重下降，但在1型糖尿病胰岛素治疗中加入艾塞那肽26周后，未观察到骨代谢的变化。

原文出处：

Johansen NJ, Dejgaard TF, Lund A,et al.Effects of short-acting exenatide added three times daily to insulin therapy on bone metabolism in type 1 diabetes.Diabetes Obes Metab 2021 Oct 06

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2022-04-11 ms9608593228839890

#DIA#

32 0
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2022-10-22 baoya

#胰岛#

34 0
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2021-12-06 一闲

#MET#

27 0
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authenticateStatus=null, createdAvatar=null, createdBy=cbaa3702209, createdName=pandamao2011, createdTime=Thu Nov 11 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1475164, encodeId=aed114e5164a4, 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=37, 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 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
2021-12-20 木头人513

#Diabetes#

34 0
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createdName=guojianrong, createdTime=Fri Feb 18 06:22:07 CST 2022, time=2022-02-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639947, encodeId=ef99163994ee5, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, 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=Mon Apr 11 04:22:07 CST 2022, time=2022-04-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1750278, encodeId=547b1e50278fa, content=<a href='/topic/show?id=be7c8385345' target=_blank style='color:#2F92EE;'>#胰岛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83853, encryptionId=be7c8385345, topicName=胰岛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a7a536274692, createdName=baoya, createdTime=Sat Oct 22 14:22:07 CST 2022, time=2022-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896939, encodeId=8c3e18969395e, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Dec 06 05:22:07 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1902665, encodeId=c6681902665d5, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, 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href='/topic/show?id=4a9886e56ed' target=_blank style='color:#2F92EE;'>#艾塞那肽#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86756, encryptionId=4a9886e56ed, topicName=艾塞那肽)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/UdV6ialcayj7Qv8RQm1mVfNYPKxjiaolxwglAZpCo6CwjTicOroW2Xb0Kxnc65viaxGpkuqHW7WzzbYgRLw3qooDoA/132, createdBy=04c22500137, createdName=紫砂壶, createdTime=Thu Nov 11 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422483, encodeId=028a142248336, content=<a href='/topic/show?id=ded51015e6b3' target=_blank style='color:#2F92EE;'>#骨代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101576, encryptionId=ded51015e6b3, topicName=骨代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cbaa3702209, createdName=pandamao2011, createdTime=Thu Nov 11 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1475164, encodeId=aed114e5164a4, 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=37, 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 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
2022-09-21 ms5439512287675881

#BET#

41 0
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createdName=guojianrong, createdTime=Fri Feb 18 06:22:07 CST 2022, time=2022-02-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639947, encodeId=ef99163994ee5, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, 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=Mon Apr 11 04:22:07 CST 2022, time=2022-04-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1750278, encodeId=547b1e50278fa, content=<a href='/topic/show?id=be7c8385345' target=_blank style='color:#2F92EE;'>#胰岛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83853, encryptionId=be7c8385345, topicName=胰岛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a7a536274692, createdName=baoya, createdTime=Sat Oct 22 14:22:07 CST 2022, time=2022-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896939, encodeId=8c3e18969395e, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Dec 06 05:22:07 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1902665, encodeId=c6681902665d5, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, 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=Mon Dec 20 05:22:07 CST 2021, time=2021-12-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761750, encodeId=bdc71e6175054, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, 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=Wed Sep 21 19:22:07 CST 2022, time=2022-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1393626, encodeId=2f0513936263b, content=<a href='/topic/show?id=4a9886e56ed' target=_blank style='color:#2F92EE;'>#艾塞那肽#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86756, encryptionId=4a9886e56ed, topicName=艾塞那肽)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/UdV6ialcayj7Qv8RQm1mVfNYPKxjiaolxwglAZpCo6CwjTicOroW2Xb0Kxnc65viaxGpkuqHW7WzzbYgRLw3qooDoA/132, createdBy=04c22500137, createdName=紫砂壶, createdTime=Thu Nov 11 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422483, encodeId=028a142248336, content=<a href='/topic/show?id=ded51015e6b3' target=_blank style='color:#2F92EE;'>#骨代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101576, encryptionId=ded51015e6b3, topicName=骨代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cbaa3702209, createdName=pandamao2011, createdTime=Thu Nov 11 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1475164, encodeId=aed114e5164a4, 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=37, 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 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
2021-11-11 紫砂壶

#艾塞那肽#

55 0
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encryptionId=be7c8385345, topicName=胰岛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a7a536274692, createdName=baoya, createdTime=Sat Oct 22 14:22:07 CST 2022, time=2022-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896939, encodeId=8c3e18969395e, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Dec 06 05:22:07 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1902665, encodeId=c6681902665d5, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, 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2021-11-11 pandamao2011

#骨代谢#

44 0
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encryptionId=be7c8385345, topicName=胰岛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a7a536274692, createdName=baoya, createdTime=Sat Oct 22 14:22:07 CST 2022, time=2022-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896939, encodeId=8c3e18969395e, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Dec 06 05:22:07 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1902665, encodeId=c6681902665d5, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, 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href='/topic/show?id=4a9886e56ed' target=_blank style='color:#2F92EE;'>#艾塞那肽#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86756, encryptionId=4a9886e56ed, topicName=艾塞那肽)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/UdV6ialcayj7Qv8RQm1mVfNYPKxjiaolxwglAZpCo6CwjTicOroW2Xb0Kxnc65viaxGpkuqHW7WzzbYgRLw3qooDoA/132, createdBy=04c22500137, createdName=紫砂壶, createdTime=Thu Nov 11 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422483, encodeId=028a142248336, content=<a href='/topic/show?id=ded51015e6b3' target=_blank style='color:#2F92EE;'>#骨代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101576, encryptionId=ded51015e6b3, topicName=骨代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cbaa3702209, createdName=pandamao2011, createdTime=Thu Nov 11 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1475164, encodeId=aed114e5164a4, 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=37, 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 12:22:07 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
2021-11-11 xue8604

#糖尿病患者#

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Diabetes Obes Metab：每日三次的基础胰岛素治疗中加入短效艾塞那肽对1型糖尿病患者骨代谢的影响

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