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盘点:近期2型糖尿病重要研究进展一览

2017-06-11 MedSci MedSci原创

2型糖尿病患者体内产生胰岛素的能力并非完全丧失,有的患者体内胰岛素甚至产生过多,但胰岛素的作用效果较差,因此患者体内的胰岛素是一种相对缺乏,可以通过某些口服药物刺激体内胰岛素的分泌。但到后期仍有一些病人需要使用胰岛素治疗。这里梅斯小编整理了近期关于2型糖尿病的重要研究进展与大家一同分享。【1】Hypertension:高血压伴2型糖尿病患者的总体/心血管风险如何?近日,心血管权威杂志Hyper

2型糖尿病患者体内产生胰岛素的能力并非完全丧失,有的患者体内胰岛素甚至产生过多,但胰岛素的作用效果较差,因此患者体内的胰岛素是一种相对缺乏,可以通过某些口服药物刺激体内胰岛素的分泌。但到后期仍有一些病人需要使用胰岛素治疗。这里梅斯小编整理了近期关于2型糖尿病的重要研究进展与大家一同分享。

【1】Hypertension:高血压伴2型糖尿病患者的总体/心血管风险如何?

近日,心血管权威杂志Hypertension上发表了一篇研究文章,研究人员分析了在1992年至2011年期间参加医疗检查的244816名正常血压参与者和99720名高血压患者(包括7480例2型糖尿病患者),试图明确高血压糖尿病患者和非糖尿病患者之间在总体/心血管风险上的显著差异。

研究人员平均随访了12.7年,报告了14050例全因死亡患者。从正常血压到高血压人群,总体/心血管风险显著增加。糖尿病高血压患者的死亡率显著高于非糖尿病高血压患者。血流动力学指标和总体/心血管风险之间没有相互作用,表明血压因素,即使在药物治疗期间,也不能解释的糖尿病和非糖尿病的高血压患者死亡率之间的差异。

研究人员采用横截面回归模型发现参与者较高的教育水平、低水平的焦虑和抑郁与和糖尿病高血压患者的总体死亡率降低之间存在显著的相关性,而肾功能受损、卒中心肌梗死病史以及增加的酒精和烟草消耗量与增加的死亡率显著相关。单独的血压和血糖控制不能逆转糖尿病高血压患者的总体/心血管风险。(文章详见——Hypertension:高血压伴2型糖尿病患者的总体/心血管风险如何?



【2】Diabetes:2型糖尿病患者miRNA-29表达可以影响骨骼肌葡萄糖和脂质代谢!

近日,糖尿病领域权威杂志Diabetes上发表了一篇研究文章,研究人员旨在明确miR-29家族对糖代谢和脂质代谢以及骨骼肌中胰岛素反应的影响。

研究人员提供的实验证据表明,2型糖尿病患者的骨骼肌中的miR-29a和miR-29c是明显升高的,而在健康青年人和大鼠进行耐力训练后,其骨骼肌中的miR-29a和miR-29c水平有所减低。在原代培养的人类骨骼肌细胞中,抑制和过度表达的实验结果表明miR-29a和miR-29c调节葡萄糖摄取和胰岛素刺激的葡萄糖代谢。研究人员发现miR-29过表达可以减弱胰岛素信号以及IRS1和PI3K的表达。此外,miR-29过表达可以降低HK2的表达和活性。相反,通过电穿孔使小鼠胫骨前肌细胞过表达miR-29可以减少葡萄糖摄取,以及降低糖原水平,伴随着降低GLUT4表达。

研究人员提供的证据表明脂肪酸氧化可以被miR-29过表达进行负性调控,可能是通过调节PGC1α的表达来实现。总的来说,该研究揭示了miR-29作为胰岛素刺激葡萄糖代谢和脂质过氧化的重要调节因子,与人体生理功能和2型糖尿病具有相关性。(文章详见——Diabetes:2型糖尿病患者miRNA-29表达可以影响骨骼肌葡萄糖和脂质代谢!

【3】Diabetes:家族性高胆固醇血症与2型糖尿病有何关系?

最近已有研究表明与低水平的低密度脂蛋白胆固醇(LDL-C)相关的等位基因与2型糖尿病的风险增加相关,这突出了LDL-C和糖尿病之间的复杂关系。近期研究报道了与年龄匹配的亲属没有FH的亲属相比,FH个体自我报告的糖尿病患病率仍然较低。

近日,糖尿病领域权威杂志Diabetes上发表了一篇研究文章,为了扩大这种观察现象,研究人员在一个大型的阿米什人群中评估了FH与糖尿病状态和血糖之间相关性,这个阿米什人群富集了FH相关的APOB R3527Q 变异,其包含了640名APOB R3527Q携带者和4683名非携带者。每一份的R3527Q T等位基因拷贝与LDL-C增加74.9毫克/分升有关,在有(5.2%)和无(4.5%)R3527Q等位基因的个体之间2型糖尿病的患病率的差异较少(P=0.23),也与空腹血糖、空腹血糖和胰岛素,或口服葡萄糖耐量(OGTT)衍生的指标没有任何相关性。

研究人员的数据没有提供证据支持APOB R3527Q变异与2型糖尿病或血糖之间存在相关性,并且突出了LDL-C与2型糖尿病之间的不对称性关系,和/或基因/变异依赖的LDL-C与2型糖尿病之间相关性的特异性。(文章详见——Diabetes:家族性高胆固醇血症与2型糖尿病有何关系?



【4】Diabetologia:出生季节可能预示着你有更高几率患成人2型糖尿病!

2017年5月,发表在《Diabetologia》的一项由中国科学家进行的针对50万中国成年人的前瞻性队列研究,得出了出生季节与患成人2型糖尿病的风险相关的结论。

研究对象是来自于2004~2008年间在China Kadoorie Biobank登记的人,且随访截至2013年12月31日。在基线排除癌症、心脏病、卒中和糖尿病患者后,当前研究纳入男性189153人和女性272058人,年龄在30~79岁。
结果,在整个队列中,与夏天出生的研究对象相比,春天、秋天和冬天出生的研究对象的调整HR(95% CIs)分别为1.09(1.02,1.16)、1.08(1.02,1.15)和1.09(1.02,1.15)。这种相关性在男性和女性中一致,在后来生活的住处和生活方式因素定义的亚组中也一致。(文章详见——Diabetologia:出生季节可能预示着你有更高几率患成人2型糖尿病!

【5】Am J Hum Genet:糖尿病研究新发现——引发2型糖尿病的“根源”!

根据UCL主导的伦敦帝国理工学院的研究,科学家们通过确定人类基因组上111个新的染色体位置(“基因位点”),更进一步理解了引发2型糖尿病的基因学原因。

在由该研究小组确定的其他111个位点中,93个(84%)位于非洲裔美国人和欧洲人群中,只有18个是特异性属于欧洲人的。研究人员分析包含5800名2型糖尿病病例受试者和9691名对照受试者的欧洲和非洲裔美国人样本群体,显示跨基因组的调控热点的多个2型糖尿病基因位点。

发现额外的111个位点和以前已知的76个位点调节至少266个与所鉴定的疾病位点相邻的基因的表达。绝大多数这些基因位点被发现在基因编码区之外,但与在体脂中表达的调节这些基因的调节“热点”相吻合。

在94名欧洲2型糖尿病患者和94名对照受试者的独立样本中进一步分析了非洲裔美国人和欧洲人群中的三个位点,以鉴定导致该疾病的基因突变。结果发现,所有三个基因位点与含有多种调节元件和表观遗传标记的染色体区域重叠,并且可以进一步研究2型糖尿病的候选因子突变。(文章详见——Am J Hum Genet:糖尿病研究新发现——引发2型糖尿病的“根源”!




【6】SCI REP:红细胞分布宽度是2型糖尿病患者用药及预后的重要指标!

近日,Scientific reports 杂志上发表了一篇研究文章,研究人员共纳入了809名2型糖尿病患者,将其按红细胞分布宽度大小的四分位数分为4组:Q1≤12.4(n=229),12.4
研究人员发现相比于Q1组,Q4组患者年龄较大、病程较长、收缩压较高、血尿素氮水平较高、肌酐较高、尿酸以及蛋白尿水平较高,但是血红蛋白、血清白蛋白和糖化血红蛋白均有所降低。此外,相比于Q1组患者,Q3组和Q4组患者糖尿病肾病、糖尿病周围神经病变、高血压和冠心病的发生率也明显增高。药物,包括钙通道阻滞剂和抗血小板治疗在Q3或Q4组的使用频率也要显著高于Q1组。

此外,Logistic回归分析表明抗血小板治疗(比值比为2.065)、高血压(比值比为2.819)、肌酐(比值比为4.473)和蛋白尿(比值比为2.085)与Q4组水平呈正相关,但较高的血红蛋白(比值比为0.021)和血清钙水平(比值比为0.178)与Q4组呈负相关。(文章详见——SCI REP:红细胞分布宽度是2型糖尿病患者用药及预后的重要指标!

【7】Nature:中国科学家研发2型糖尿病新药有重要突破


日前,国际顶级学术期刊《自然》同时在线发表了两项重大成果。中科院上海药物研究所领衔成功解析人源胰高血糖素受体全长蛋白的三维结构,上海科技大学iHuman研究所领衔成功解析人源胰高血糖素样肽1受体七次跨膜区晶体结构。这两个发现为研发治疗2型糖尿病的新药提供了重要的结构生物学基础。此外,iHuman研究所领衔成功解析了人源平滑受体的多结构域三维结构,这是抗肿瘤药物的重要靶点。

科学家发现,细胞表面存在着一种蛋白质,即GPCR,充当了“信号兵”,在细胞信号转导中发挥非常关键的作用。由于获得稳定的完整GPCR蛋白难度极大,只能“分而解之”,其全长结构一直未被解析,因而成为国内外该研究领域的焦点和热点。最近,上海药物所研究员吴蓓丽、王明伟和蒋华良等三个课题组联手国际伙伴,用两年半时间筛选了200余种重组蛋白表达载体,首次在较高分辨率水平测定了胰高血糖素受体全长蛋白的三维结构。(文章详见——Nature:中国科学家研发2型糖尿病新药有重要突破


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createdName=执着追梦, createdTime=Sun Jun 11 14:31:27 CST 2017, time=2017-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=209421, encodeId=764820942176, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4FADCE0F987688.jpg, createdBy=23af1632396, createdName=1dd8f26bm82(暂无匿称), createdTime=Sun Jun 11 13:58:51 CST 2017, time=2017-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=209417, encodeId=451b20941ead, content=糖尿病患者注意, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 11 13:53:59 CST 2017, time=2017-06-11, status=1, ipAttribution=)]
    2017-06-12 惠映实验室

    学习了,谢谢。

    0

  3. 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createdName=flysky120, createdTime=Sun Jun 11 13:53:59 CST 2017, time=2017-06-11, status=1, ipAttribution=)]
    2017-06-12 天涯183

    非常好的文章,学习了,很受益

    0

  4. 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createdName=flysky120, createdTime=Sun Jun 11 13:53:59 CST 2017, time=2017-06-11, status=1, ipAttribution=)]
    2017-06-11 dhzzm

    学习了分享了

    0

  5. 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createdName=flysky120, createdTime=Sun Jun 11 13:53:59 CST 2017, time=2017-06-11, status=1, ipAttribution=)]
    2017-06-11 jianzhang20

    非常有价值,高血压和高血脂均是高血糖重要影响因素

    0

  6. 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createdName=flysky120, createdTime=Sun Jun 11 13:53:59 CST 2017, time=2017-06-11, status=1, ipAttribution=)]
    2017-06-11 xiaotaiyang1

    看看了解一下,谢谢

    0

  7. 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createdName=flysky120, createdTime=Sun Jun 11 13:53:59 CST 2017, time=2017-06-11, status=1, ipAttribution=)]
    2017-06-11 180****9923

    学习了

    0

  8. 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createdName=flysky120, createdTime=Sun Jun 11 13:53:59 CST 2017, time=2017-06-11, status=1, ipAttribution=)]
    2017-06-11 执着追梦

    学习,谢谢分享

    0

  9. 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createdName=执着追梦, createdTime=Sun Jun 11 14:31:27 CST 2017, time=2017-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=209421, encodeId=764820942176, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4FADCE0F987688.jpg, createdBy=23af1632396, createdName=1dd8f26bm82(暂无匿称), createdTime=Sun Jun 11 13:58:51 CST 2017, time=2017-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=209417, encodeId=451b20941ead, content=糖尿病患者注意, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 11 13:53:59 CST 2017, time=2017-06-11, status=1, ipAttribution=)]
    2017-06-11 1dd8f26bm82(暂无匿称)

    好资源

    0

  10. 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19:20:32 CST 2017, time=2017-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=209477, encodeId=6d5e2094e799, content=非常有价值,高血压和高血脂均是高血糖重要影响因素, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/29/541980d6610d2b4a4fa824b8791752d4.jpg, createdBy=a132103005, createdName=jianzhang20, createdTime=Sun Jun 11 19:13:02 CST 2017, time=2017-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=209471, encodeId=79ce2094e17e, content=看看了解一下,谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=90f31612316, createdName=xiaotaiyang1, createdTime=Sun Jun 11 18:18:01 CST 2017, time=2017-06-11, status=1, 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createdName=flysky120, createdTime=Sun Jun 11 13:53:59 CST 2017, time=2017-06-11, status=1, ipAttribution=)]
    2017-06-11 flysky120

    糖尿病患者注意

    0

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