title: 1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death.
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.
authors.affiliation: Computational Medicine Research Group, Laboratory of Computational Engineering, Systems Biology and Bioinformation Technology, Helsinki University of Technology, Finland.
authors.forename: Ville-Petteri
authors.initials: VP
authors.lastname: Mäkinen
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.forename: Maija
authors.initials: M
authors.lastname: Parkkonen
authors.forename: Petri
authors.initials: P
authors.lastname: Ingman
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kaski
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
mesh_terms: D000085:Acetates / Q000097:blood; D000328:Adult; D000419:Albuminuria / Q000378:metabolism; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D048909:Diabetes Complications / Q000401:mortality* / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood / Q000175:diagnosis; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D019344:Lactic Acid / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011522:Protons; D015203:Reproducibility of Results; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000097:blood
chemical_list: D000085:Acetates; D000959:Antihypertensive Agents; D001055:Apolipoproteins B; D015415:Biomarkers; D002784:Cholesterol; D008076:Cholesterol, HDL; D003404:Creatinine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D019344:Lactic Acid; D011522:Protons; D014280:Triglycerides; D014508:Urea