Cardiovasc Diabetol:在退伍军人糖尿病试验(VADT)中,低空腹c肽水平与心血管风险、随访时血糖变化和严重低血糖相关

2022-01-05 从医路漫漫 MedSci原创

2型糖尿病的自然病史以不同的β细胞功能模式为特征。在疾病的早期阶段,β细胞功能相对保存良好,胰岛素分泌增加,这是克服胰岛素抵抗所需更高胰岛素水平的补偿要求的一部分。

目的:2型糖尿病的自然病史以不同的β细胞功能模式为特征。在疾病的早期阶段,β细胞功能相对保存良好,胰岛素分泌增加,这是克服胰岛素抵抗所需更高胰岛素水平的补偿要求的一部分。随着糖尿病的进展,β细胞功能逐渐恶化,经常需要外源性胰岛素补充来维持血糖目标。由于高达80%的分泌胰岛素在第一次通过肝脏时被清除,所以血液中胰岛素原裂解的产物C肽的水平可以用来更好的估计β细胞的功能。低C肽水平表明β细胞功能障碍,与每日血糖变化增加和低血糖有关。在2型糖尿病的晚期,严重低血糖和血糖变异增加可预测心血管(CVD)风险。本研究调查了C肽水平与心血管疾病风险之间的关系,以及是否可以用来访期间发生的血糖变化和严重低血糖来解释。

材料和方法:本研究反映了退伍军人事务糖尿病试验(VADT, NCT00032487)数据的事后分析。作为研究基线评估的一部分,在芝加哥大学DRTC核心实验室对1791名最终VADT参与者中的1693人进行了c -肽水平的测量。VADT的设计和主要结果已在前面描述。简单地说,将2型糖尿病和血糖控制欠佳(HbA1c > 58 mmol/l[7.5%])的退伍军人随机分为强化血糖控制组和标准血糖控制组。两组患者采用相似的糖尿病药物治疗(但剂量不同),目标是使治疗组间糖化血红蛋白绝对值差异达到7.1 mmol/mol(1.5%)。每隔3个月测量糖化血红蛋白和空腹血糖,最长可达84个月。在两组中,HbA1c在3个月后下降,6个月后稳定,组间HbA1c中位数分离为7.1 mmol/mol。为了消除这种初始血糖水平的快速下降,并确保血糖变化的可靠计算,在6个月的随访后,只有1565名至少进行过两次空腹血糖测量的参与者被纳入分析。通过评估1565名退伍军人糖尿病试验参与者基线时的空腹C肽水平、综合心血管转归、严重低血糖以及就诊至就诊的空腹血糖变异系数(CV)和平均真实变异(ARV)。

结果:C肽水平与心血管病风险呈U型关系,低水平下降(<0.50nmol/l,HR 1.30[95%CI 1.05~1.60],p=0.02),高水平升高(>1.23nmol/l,1.27[1.00~1.63],p=0.05)。C肽水平与严重低血糖(OR0.68[0.60~0.77])和就诊间血糖变异(CV,标准化β-估计−为0.12SE0.01;ARV0.10[0.01])呈负相关(P均<0.0001)。低C肽水平与心血管疾病风险的关系与心脏代谢危险因素无关(1.48[1.17-1.87,p=0.001),当在具有严重低血糖和血糖变异的同一模型中测试时,低C肽水平与心血管疾病仍然相关。

图1 基线c肽水平与心血管疾病风险和血糖控制随访措施之间的关系c肽水平与CVD风险关系的限制性三次样条曲线和95% CI。阴影区域代表c肽水平的频率。b c肽水平与严重低血糖之间关系的限制性三次样条曲线和95% CI。阴影区域表示低血糖事件的百分比。c, d基线c肽水平与更新的平均访视葡萄糖CV和ARV之间的关系。降糖组调整A-D面板上所有模型。e c -肽水平低(< 0.50 nmol/l)和高(> 1.23 nmol/l)的患者在调整降血糖组(Trt组)、临床和人口统计学危险因素(RF)、基线胰岛素和磺酰脲类(SU)使用(Meds)、葡萄糖CV (G-CV)或严重低血糖(sHypo)后具有CVD风险的危险比(95% CI)。在使用限制三次样条的分析中,低(< 0.50 nmol/l)和高c肽(> 1.23 nmol/l)范围由对应于1 (a)的危险比的c肽值定义。

图2 基线c肽水平与血糖控制随访测量的关系

结论:进展期2型糖尿病患者低C肽水平与心血管风险增加有关。这种关联与血糖变异增加或严重低血糖无关。C肽水平可以预测未来的血糖控制模式和心血管风险,并识别影响晚期2型糖尿病临床决策的表型。

原文出处:

Koska J,  Nuyujukian DS,  Bahn GD,et al.Association of low fasting C-peptide levels with cardiovascular risk, visit-to-visit glucose variation and severe hypoglycemia in the Veterans Affairs Diabetes Trial (VADT).Cardiovasc Diabetol 2021 Dec 08;20(1)

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    2022-08-11 quxin068
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  4. 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style='color:#2F92EE;'>#ADT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2018, encryptionId=dd832018bd, topicName=ADT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87be7387847, createdName=124984e7m85暂无昵称, createdTime=Thu Jan 06 12:27:37 CST 2022, time=2022-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1181217, encodeId=e9f8118121eca, content=累计死亡病例548.1万例,达到, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIrrxxDxnLic8t6EAs38Qfwo6H2h6JMleIgb9OSYf6LMnVDkQEqUXWoSDWboibjhOBI9SJDTXweqQIA/132, createdBy=50aa5321359, createdName=查查佳佳, createdTime=Thu Jan 06 09:52:16 CST 2022, time=2022-01-06, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1761817, encodeId=db421e61817d4, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, 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=Mon Jul 11 01:27:37 CST 2022, time=2022-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1939300, encodeId=b5471939300fa, content=<a href='/topic/show?id=1c292818fd' target=_blank style='color:#2F92EE;'>#ASC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2818, encryptionId=1c292818fd, topicName=ASC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=74808, createdName=quxin068, createdTime=Thu Aug 11 05:27:37 CST 2022, time=2022-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1648690, encodeId=3145164869019, content=<a href='/topic/show?id=718f9464852' target=_blank style='color:#2F92EE;'>#退伍军人#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94648, encryptionId=718f9464852, topicName=退伍军人)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4e9d23641338, createdName=smlt2016, createdTime=Sun Apr 17 07:27:37 CST 2022, time=2022-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2082575, encodeId=bc2520825e501, content=<a href='/topic/show?id=56658981223' target=_blank style='color:#2F92EE;'>#血管风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89812, encryptionId=56658981223, topicName=血管风险)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/78FA0899509C358B01B975E8EAC1F88A/100, createdBy=7d822500145, createdName=ms5353107019656438, createdTime=Sun Aug 21 02:27:37 CST 2022, time=2022-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1640024, encodeId=2e261640024ac, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, 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=Thu Feb 03 07:27:37 CST 2022, time=2022-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685716, encodeId=b76b1685e160c, content=<a 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style='color:#2F92EE;'>#ADT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2018, encryptionId=dd832018bd, topicName=ADT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87be7387847, createdName=124984e7m85暂无昵称, createdTime=Thu Jan 06 12:27:37 CST 2022, time=2022-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1181217, encodeId=e9f8118121eca, content=累计死亡病例548.1万例,达到, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIrrxxDxnLic8t6EAs38Qfwo6H2h6JMleIgb9OSYf6LMnVDkQEqUXWoSDWboibjhOBI9SJDTXweqQIA/132, createdBy=50aa5321359, createdName=查查佳佳, createdTime=Thu Jan 06 09:52:16 CST 2022, time=2022-01-06, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1761817, encodeId=db421e61817d4, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, 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=Mon Jul 11 01:27:37 CST 2022, time=2022-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1939300, encodeId=b5471939300fa, content=<a href='/topic/show?id=1c292818fd' target=_blank style='color:#2F92EE;'>#ASC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2818, encryptionId=1c292818fd, topicName=ASC)], attachment=null, authenticateStatus=null, createdAvatar=null, 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style='color:#2F92EE;'>#ADT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2018, encryptionId=dd832018bd, topicName=ADT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87be7387847, createdName=124984e7m85暂无昵称, createdTime=Thu Jan 06 12:27:37 CST 2022, time=2022-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1181217, encodeId=e9f8118121eca, content=累计死亡病例548.1万例,达到, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIrrxxDxnLic8t6EAs38Qfwo6H2h6JMleIgb9OSYf6LMnVDkQEqUXWoSDWboibjhOBI9SJDTXweqQIA/132, createdBy=50aa5321359, createdName=查查佳佳, createdTime=Thu Jan 06 09:52:16 CST 2022, time=2022-01-06, status=1, ipAttribution=)]
    2022-01-06 俅侠
  9. 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    2022-01-06 查查佳佳

    累计死亡病例548.1万例,达到

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