Metabolic diversity of progressive kidney disease in 325 patients with type 1 diabetes (the FinnDiane Study).
Type 1 diabetic patients with varying severity of kidney disease were investigated to create multimetabolite models of the disease process. Urinary albumin excretion rate was measured for 3358 patients with type 1 diabetes. Prospective records were available for 1051 patients, of whom 163 showed progression of albuminuria (8.3-year follow-up), and 162 were selected as stable controls. At baseline, serum lipids, lipoprotein subclasses, and low-molecular weight metabolites were quantified by NMR spectroscopy (325 samples). The data were analyzed by the self-organizing map. In cross-sectional analyses, patients with no complications had low serum lipids, less inflammation, and better glycemic control, whereas patients with advanced kidney disease had high serum cystatin-C and sphingomyelin. These phenotype extremes shared low unsaturated fatty acids (UFAs) and phospholipids. Prospectively, progressive albuminuria was associated with high UFAs, phospholipids, and IDL and LDL lipids. Progression at longer duration was associated with high HDL lipids, whereas earlier progression was associated with poor glycemic control, increased saturated fatty acids (SFAs), and inflammation. Diabetic kidney disease consists of diverse metabolic phenotypes: UFAs, phospholipids, IDL, and LDL may be important in the subclinical phase, high SFAs and low HDL suggest accelerated progression, and the sphingolipid pathway in advanced kidney injury deserves further research.
Computational Medicine Research Group, Institute of Clinical Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu , Finland. ville-petteri.makinen@computationalmedicine.fi
Ville-Petteri
VP
Mäkinen
Tuulia
T
Tynkkynen
Pasi
P
Soininen
Tomi
T
Peltola
Antti J
AJ
Kangas
Carol
C
Forsblom
Lena M
LM
Thorn
Kimmo
K
Kaski
Reino
R
Laatikainen
Mika
M
Ala-Korpela
Per-Henrik
PH
Groop
D000328:Adult; D000419:Albuminuria; D000597:Amino Acids, Branched-Chain / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood*; D018450:Disease Progression; D005227:Fatty Acids / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D016015:Logistic Models; D008297:Male; D055442:Metabolome; D008954:Models, Biological; D010641:Phenotype; D012372:ROC Curve; D018709:Statistics, Nonparametric
D000597:Amino Acids, Branched-Chain; D015415:Biomarkers; D005227:Fatty Acids; D006442:Glycated Hemoglobin; D008074:Lipoproteins; C517652:hemoglobin A1c protein, human