CLIN PHARMACOKINET:1型糖尿病患者速效型胰岛素的药代动力学和药效学特征

2017-06-02 MedSci MedSci原创

速效胰岛素(速效天冬胰岛素)是一种新胰岛素门冬胰岛素(IAsp)制剂,它能够模拟内源性胰岛素快速释放。在六项临床药理学试验的汇总数据的事后分析中,研究人员比较了速效天冬胰岛素和IAsp的药理学特征。

近日,国际杂志CLINICAL PHARMACOKINETICS上在线发表一项关于1糖尿病患者快速反应型胰岛素的药代动力学和药效学特征的研究。

速效胰岛素(速效天冬胰岛素)是一种新胰岛素门冬胰岛素(IAsp)制剂,它能够模拟内源性胰岛素快速释放。在六项临床药理学试验的汇总数据的事后分析中,研究人员比较了速效天冬胰岛素和IAsp的药理学特征。

该分析包括来自6个随机双盲交叉试验的2181糖尿病患者的成年人。 受试者接受皮下给药(0.2U / kg)速效天冬胰岛素和IAsp。在三个试验中,进行12小时异体血糖钳夹(靶标为5.5mmol / L; 100mg / dL)以评估药效学。

Iasp相比,速效天冬胰岛素药代动力学和药效学曲线左移。开始出现为4.9分钟(95%置信区间[CI]速效天冬胰岛素-ASP[-5.3-4.4]p  <0.001),早期暴露(AUC IAsp0-30min)是两倍(估计比例速效天冬胰岛素/ IAsp 2.01 [1.87-2.17]p  <0.001)和暴露偏移(t 50Cmax)发生在12.2分钟前[-17.9-6.5]p  <0.001)。 因此,早期起效提早4.9分钟[-6.9-3.0]p  <0.001),早期葡萄糖降低作用(AUC GIR0-30min)出现74%(1.74 [1.47-2.10]p  <0.001 )和葡萄糖降低作用(t 50GIRmax)的偏移发生提前14.3分钟 [-22.1-6.5]p  <0.001)。治疗前总暴露量和总葡萄糖降低作用差异不显著。

研究表明,速效天冬胰岛素有可能更好地模拟生理膳食胰岛素分泌,与IAsp相比,能够改善餐后葡萄糖控制。

原始出处:

Tim Heise, Thomas R. Pieber, Thomas Danne. et.al. A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults with Type 1 Diabetes. Clin Pharmacokinet (2017) 56: 559.

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    2017-10-21 canlab
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createdName=canlab, createdTime=Sat Oct 21 23:49:00 CST 2017, time=2017-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1968228, encodeId=5299196822826, content=<a href='/topic/show?id=a4b96e542' target=_blank style='color:#2F92EE;'>#1型糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=675, encryptionId=a4b96e542, topicName=1型糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0e3195, createdName=millore, createdTime=Mon Mar 26 21:49:00 CST 2018, time=2018-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1718896, encodeId=21101e18896e7, content=<a href='/topic/show?id=cf168e59360' target=_blank style='color:#2F92EE;'>#药效学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87593, 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channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Thu Apr 05 18:49:00 CST 2018, time=2018-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1666656, encodeId=5fcd166665661, content=<a href='/topic/show?id=df6a8e287d7' target=_blank style='color:#2F92EE;'>#药代#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87287, encryptionId=df6a8e287d7, topicName=药代)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bccf26064950, createdName=fengyqf, createdTime=Fri Dec 22 06:49:00 CST 2017, time=2017-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787263, encodeId=002b1e8726340, content=<a 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351259, encodeId=a84c13512590c, content=<a href='/topic/show?id=9ac28e2893e' target=_blank style='color:#2F92EE;'>#药代动力学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87289, encryptionId=9ac28e2893e, topicName=药代动力学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sun Jun 04 05:49:00 CST 2017, time=2017-06-04, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1908266, encodeId=edd7190826611, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Mon Dec 04 07:49:00 CST 2017, time=2017-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733875, encodeId=069b1e3387510, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, 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channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Thu Apr 05 18:49:00 CST 2018, time=2018-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1666656, encodeId=5fcd166665661, content=<a href='/topic/show?id=df6a8e287d7' target=_blank style='color:#2F92EE;'>#药代#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87287, encryptionId=df6a8e287d7, topicName=药代)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bccf26064950, createdName=fengyqf, createdTime=Fri Dec 22 06:49:00 CST 2017, time=2017-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787263, encodeId=002b1e8726340, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Mon Aug 14 16:49:00 CST 2017, time=2017-08-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1672300, encodeId=a4e716e2300af, content=<a href='/topic/show?id=2f3a8e59170' target=_blank style='color:#2F92EE;'>#药效#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87591, encryptionId=2f3a8e59170, topicName=药效)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=189026903389, createdName=lsndxfj, createdTime=Wed Nov 22 20:49:00 CST 2017, time=2017-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351259, encodeId=a84c13512590c, content=<a href='/topic/show?id=9ac28e2893e' target=_blank style='color:#2F92EE;'>#药代动力学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87289, encryptionId=9ac28e2893e, topicName=药代动力学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sun Jun 04 05:49:00 CST 2017, time=2017-06-04, status=1, ipAttribution=)]
    2017-06-10 baoya
  6. [GetPortalCommentsPageByObjectIdResponse(id=1908266, encodeId=edd7190826611, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Mon Dec 04 07:49:00 CST 2017, time=2017-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733875, encodeId=069b1e3387510, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, 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channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Thu Apr 05 18:49:00 CST 2018, time=2018-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1666656, encodeId=5fcd166665661, content=<a href='/topic/show?id=df6a8e287d7' target=_blank style='color:#2F92EE;'>#药代#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87287, encryptionId=df6a8e287d7, topicName=药代)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bccf26064950, createdName=fengyqf, createdTime=Fri Dec 22 06:49:00 CST 2017, time=2017-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787263, encodeId=002b1e8726340, content=<a 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351259, encodeId=a84c13512590c, content=<a href='/topic/show?id=9ac28e2893e' target=_blank style='color:#2F92EE;'>#药代动力学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87289, encryptionId=9ac28e2893e, topicName=药代动力学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sun Jun 04 05:49:00 CST 2017, time=2017-06-04, status=1, ipAttribution=)]
    2018-04-05 yb6560
  7. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351259, encodeId=a84c13512590c, content=<a href='/topic/show?id=9ac28e2893e' target=_blank style='color:#2F92EE;'>#药代动力学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87289, encryptionId=9ac28e2893e, topicName=药代动力学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sun Jun 04 05:49:00 CST 2017, time=2017-06-04, status=1, ipAttribution=)]
    2017-12-22 fengyqf
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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351259, encodeId=a84c13512590c, content=<a href='/topic/show?id=9ac28e2893e' target=_blank style='color:#2F92EE;'>#药代动力学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87289, encryptionId=9ac28e2893e, topicName=药代动力学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sun Jun 04 05:49:00 CST 2017, time=2017-06-04, status=1, ipAttribution=)]
    2017-08-14 jj000001
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既往的研究发现骨折风险的增加与1型糖尿病(T1DM)之间的联系仍然无法由传统的危险因素来解释,如面积骨密度(aBMD)。然而,一些数据发现在T1DM患者中存在影响骨强度的其他决定因素,如体积骨密度(vBMD)和骨几何学。因此,研究人员进行了一项研究,比较了成人T1DM患者的面积和体积骨骼参数及皮质骨几何学,通过性别和年龄匹配对照组。该研究是一项横断面研究,包括64名成人T1DM患者(38名男性,4

Nature Medicine: 发现一型胰岛素突变引起1型糖尿病病

这项研究发现了临床中存在的一种新的来自非正常翻译而产生的突变型胰岛素蛋白,并且揭示其足以能够作为自身T细胞的抗原,从而介导杀死胰岛的β细胞,引起1型糖尿病。这一新抗原的发现,作为未来开发中和抗体,为抑制T细胞免疫的反生,提供了理论基础。未来可以因此,筛选含有这一基因突变的1型糖尿病病人,而对此采取个性化疗法。

Diabetologia:母亲饮食中的脂肪酸可降低儿童患1型糖尿病的风险

发表在《糖尿病学》(欧洲糖尿病研究学会 [EASD] 的期刊杂志)上的一项新研究显示,婴幼儿在母亲怀孕期或哺乳期获得的主要来源于鱼类的omega-3多元不饱和脂肪酸(PUFAs),可以帮助他们降低患1型糖尿病(T1D)的风险。