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

Ville-Petteri Makinen, Pasi Soininen, Carol Forsblom, Maija Parkkonen, Petri Ingman, Kimmo Kaski, Per Henrik Groop, Mika Ala-Korpela

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number167
JournalMolecular Systems Biology
Volume4
DOIs
Publication statusPublished - 20 Feb 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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