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Acylcarnitines and prediction of renal function decline in type 2 diabetes.
BMJ Open Diab. Res. Care 14:e005748 (2026)
Introduction
We comprehensively investigated whether serum acylcarnitine levels are
associated with and predict the decline of glomerular filtration rate
(GFR) in type 2 diabetes.Research design and methods
Two cohorts of patients with type 2 diabetes were investigated: a
subset of the aggregate Gargano Mortality Study (aGMS, n=575; 9 years of
median follow-up; mean age=60.9±9.8; mean diabetes duration=11.6±9.3)
as a discovery set from Italy. A sample from the Joslin Kidney Study
(JKS, n=252; 10 years of median follow-up; mean age=57.8±5.6; mean
diabetes duration=14.2±7.6) was used as an independent validation set
with different environmental and ethnic background for some associated
metabolites in the aGMS.Main outcome estimated GFR (eGFR) change over time (mL/min/1.73 m2/year).Results
Eleven out of the 40 acylcarnitines (by the AbsoluteIDQTM p180 Kit,
BIOCRATES) were significantly associated with the rate of eGFR decline
after Bonferroni correction. All 11 molecules were internally validated
(p<0.05). Most of these associations survived the adjustment for
several confounders, including age, sex, smoking habit, body mass index,
glycated hemoglobin, disease duration, albumin excretion rate,
triglycerides, low-density lipoprotein and statins treatment
(p<0.05). Tiglylcarnitine and methylglutarylcarnitine, but not
tetradecenoylcarnitine and hexadecenoylcarnitine, were also associated
with eGFR decline in the JKS (p<0.05). Using multivariable least
absolute shrinkage and selection operator regression analysis,
methylglutarylcarnitine, hydroxyvalerylcarnitine, hexenoylcarnitine,
decadienylcarnitine, dodecanedioylcarnitine, tetradecadienylcarnitine
were independently associated with kidney function decline. The pairwise
correlation among these ranged from −0.02 to 0.55. An acylcarnitine
score comprising these six molecules improved discrimination (p<0.01)
and reclassification (p<0.001) of two clinical prediction models of
GFR decline in diabetes.Conclusions
In patients with type 2 diabetes, four short, three medium and four
long-chain acylcarnitines are associated with the rate of kidney
function decline. Adding the acylcarnitine score to clinical prediction
models improves the identification of individuals who are at greater
risk of progression to kidney failure.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Renal Function ; Diabetes Mellitus ; Type 2 Diabetes ; Kidney Disease ; Body Mass Index ; Linear Regression ; Glycated Hemoglobin ; Excretion
ISSN (print) / ISBN
2052-4897
e-ISSN
2052-4897
Quellenangaben
Volume: 14,
Issue: 3,
Article Number: e005748
Publisher
BMJ Publishing Group
Publishing Place
London
Reviewing status
Peer reviewed