1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death.
1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death.
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DOI：
10.1038/msb4100205
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发表时间：
2008
影响因子：
9.9
通讯作者：
中科院分区：
文献类型：
--
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微妙的代谢变化发生在慢性血管并发症之前并伴随慢性血管并发症，这是糖尿病过早死亡的主要原因。为了获得这些高风险个体的多代谢物特征，我们测量了613例I型糖尿病患者血清中的质子核磁共振（1H NMR）数据，这些患者有多种并发症。我们开发了一个新的代谢组学框架来可视化和解释数据，并将代谢谱与基础诊断和生化变量联系起来。我们的研究结果表明糖尿病肾病、胰岛素抵抗和代谢综合征之间存在复杂的相互作用。我们说明了一个单一的1H NMR协议是如何能够确定多诊断代谢物歧管的I型糖尿病及其改变如何转化为临床表型，集群的微血管和大血管并发症，并在几年的随访死亡率。这项工作证明了复杂血管疾病的弥漫性和单一诊断生物标志物的局限性。然而，它也承诺通过高通量分析和先进的计算方法提供具有成本效益的解决方案，如在代表真实的临床情况的病例中所应用的。
Subtle metabolic changes precede and accompany chronic vascular complications, which are the primary causes of premature death in diabetes. To obtain a multimetabolite characterization of these high-risk individuals, we measured proton nuclear magnetic resonance (1H NMR) data from the serum of 613 patients with type I diabetes and a diverse spread of complications. We developed a new metabonomics framework to visualize and interpret the data and to link the metabolic profiles to the underlying diagnostic and biochemical variables. Our results indicate complex interactions between diabetic kidney disease, insulin resistance and the metabolic syndrome. We illustrate how a single 1H NMR protocol is able to identify the polydiagnostic metabolite manifold of type I diabetes and how its alterations translate to clinical phenotypes, clustering of micro- and macrovascular complications, and mortality during several years of follow-up. This work demonstrates the diffuse nature of complex vascular diseases and the limitations of single diagnostic biomarkers. However, it also promises cost-effective solutions through high-throughput analytics and advanced computational methods, as applied here in a case that is representative of the real clinical situation.
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影响因子：
7.7
作者：
Caramori, ML;Fioretto, P;Mauer, M
通讯作者：
Mauer, M
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Finne, P;Reunanen, A;Grönhagen-Riska, C
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Grönhagen-Riska, C
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Hakonarson, Hakon;Grant, Struan F. A.;Polychronakos, Constantin
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Polychronakos, Constantin
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Yusuf, S
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Grundy, SM;Becker, D;Jehle, AJ
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Jehle, AJ