Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes

Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes

Aims/hypothesis This prospective, observational study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in individuals with type 1 diabetes by employing an automated NMR metabolomics technique suitable for large-scale urine sample collections. Metho...

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Bibliographic Details
Published in:Diabetologia Vol. 65; no. 1; pp. 140 - 149
Main Authors: Mutter, Stefan, Valo, Erkka, Aittomäki, Viljami, Nybo, Kristian, Raivonen, Lassi, Thorn, Lena M., Forsblom, Carol, Sandholm, Niina, Würtz, Peter, Groop, Per-Henrik
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-01-2022
Springer Nature B.V
Subjects:
Albuminuria - metabolism
Amino acids
Citric acid
Creatinine
Diabetes
Diabetes mellitus (insulin dependent)
Diabetes Mellitus, Type 1 - complications
Diabetic Nephropathies - metabolism
Diabetic nephropathy
Disease Progression
End-stage renal disease
Human Physiology
Humans
Internal Medicine
Isoleucine
Kidney diseases
Medicine
Medicine & Public Health
Metabolic Diseases
Metabolites
Metabolomics
Nephropathy
NMR
Nuclear magnetic resonance
Population studies
Prospective Studies
Threonine
Valine
Progression
Diabetic nephropathy
NMR
Type 1 diabetes
Metabolite profiling
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Summary:Aims/hypothesis This prospective, observational study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in individuals with type 1 diabetes by employing an automated NMR metabolomics technique suitable for large-scale urine sample collections. Methods We collected 24-h urine samples for 2670 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy study and measured metabolite concentrations by NMR. Individuals were followed up for 9.0 ± 5.0 years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regressions were performed on the entire study population (overall progression), on 1999 individuals with normoalbuminuria and 347 individuals with macroalbuminuria at baseline. Results Seven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage ( p  < 8 × 10 −4 ): leucine (HR 1.47 [95% CI 1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-Hydroxyisobutyrate was associated with overall progression (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria. Conclusions/interpretation Branched-chain amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts. Graphical abstract
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ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-021-05584-3