1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death.
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.
Mäkinen
Ville-Petteri
VP
Computational Medicine Research Group, Laboratory of Computational Engineering, Systems Biology and Bioinformation Technology, Helsinki University of Technology, Finland.
Soininen
Pasi
P
Forsblom
Carol
C
Parkkonen
Maija
M
Ingman
Petri
P
Kaski
Kimmo
K
Groop
Per-Henrik
PH
Ala-Korpela
Mika
M
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
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