1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death

作者：Ville‐Petteri Mäkinen, Pasi Soininen, Carol M. Forsblom, Maija Parkkonen, Petri Ingman, Kimmo K. Kaski, Per‐Henrik Groop, Mika Ala‐Korpela · 发表于：Molecular Systems Biology · 年份：2008 · DOI：10.1038/msb4100205 · 被引用次数：157 · 研究领域：Metabolomics and Mass Spectrometry Studies、Liver Disease Diagnosis and Treatment、Cardiovascular Function and Risk Factors

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. People with diabetes are at high risk of dying from heart disease and stroke, and many patients also suffer from severe degradation of the kidneys, retina and nervous system. Diabetes‐related diseases reflect the imbalance of glucose...