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

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Mutter , S , Valo , E , Aittomäki , V , Nybo , K , Raivonen , L , Thorn , L M , Forsblom , C , Sandholm , N , Würtz , P & Groop , P-H 2022 , ' Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes ' , Diabetologia , vol. 65 , no. 1 , pp. 140-149 . https://doi.org/10.1007/s00125-021-05584-3

Title: Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes
Author: Mutter, Stefan; Valo, Erkka; Aittomäki, Viljami; Nybo, Kristian; Raivonen, Lassi; Thorn, Lena M.; Forsblom, Carol; Sandholm, Niina; Würtz, Peter; Groop, Per-Henrik
Contributor organization: Clinicum
Nefrologian yksikkö
HUS Abdominal Center
CAMM - Research Program for Clinical and Molecular Metabolism
Research Programs Unit
Department of General Practice and Primary Health Care
Medicum
Department of Medicine
Per Henrik Groop / Principal Investigator
Date: 2022-01
Language: eng
Number of pages: 10
Belongs to series: Diabetologia
ISSN: 0012-186X
DOI: https://doi.org/10.1007/s00125-021-05584-3
URI: http://hdl.handle.net/10138/340537
Abstract: 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 x 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.
Subject: Diabetic nephropathy
Metabolite profiling
NMR
Progression
Type 1 diabetes
INSULIN-RESISTANCE
AMINO-ACIDS
KIDNEY
ASSOCIATION
DISEASE
DIVERSITY
SIGNATURE
TRANSPORT
BLOOD
GFR
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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