Plasma levels of carboxylic acids are markers of early kidney dysfunction in
young people with type 1 diabetes.
Authors Vigers T, Vinovskis C, Li LP, Prasad P, Heerspink H, D'Alessandro A, Reisz JA,
Piani F, Cherney DZ, van Raalte DH, Nadeau KJ, Pavkov ME, Nelson RG, Pyle L,
Bjornstad P
Submitted By Submitted Externally on 6/13/2022
Status Published
Journal Pediatric nephrology (Berlin, Germany)
Year 2022
Date Published 5/1/2022
Volume : Pages Not Specified : Not Specified
PubMed Reference 35507146
Abstract We compared plasma metabolites of amino acid oxidation and the tricarboxylic
acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and
related the metabolites to glomerular filtration rate (GFR), renal plasma flow
(RPF), and albuminuria. Metabolites associated with impaired kidney function may
warrant future study as potential biomarkers or even future interventions to
improve kidney bioenergetics., Metabolomic profiling of fasting plasma samples
using a targeted panel of 644 metabolites and an untargeted panel of 19,777
metabolites was performed in 50 youth with T1DM = 10 years and 20 controls. GFR
and RPF were ascertained by iohexol and p-aminohippurate clearance, and
albuminuria calculated as urine albumin to creatinine ratio. Sparse partial
least squares discriminant analysis and moderated t tests were used to identify
metabolites associated with GFR and RPF., Adolescents with and without T1DM were
similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ±
3.7 kg/m2), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min)
and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and
the TCA cycle were significantly lower in adolescents with T1DM vs. controls,
and the measured metabolites were able to discriminate diabetes status with an
AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33,
q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02),
phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r:
-0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04),
and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r:
-0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q =
0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower
histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR., In
conclusion, adolescents with relatively short T1DM duration exhibited lower
plasma levels of carboxylic acids that associated with hyperfiltration and
hyperperfusion., NCT03618420 and NCT03584217 A higher
resolution version of the Graphical abstract is available as Supplementary