Can circulating metabolites improve identification of patients with type 2 diabetes (T2DM) at greater risk of kidney function decline? A multicohort observational study published in the BMJ Open Diabetes Research & Care evaluated the relationship between serum acylcarnitines and estimated glomerular filtration rate (eGFR) decline in T2DM.

The analysis included 575 participants from the aggregate Gargano Mortality Study (aGMS) in Italy and 252 participants from the Joslin Kidney Study (JKS) validation cohort. Median follow-up was 9 years in aGMS and 10 years in JKS. The primary outcome was longitudinal change in eGFR measured as mL/min/1.73 m²/year.

Among 40 measured acylcarnitines, 11 were significantly associated with faster eGFR decline after Bonferroni correction. All 11 metabolites were internally validated. Most associations remained significant after adjustment for age, sex, smoking status, body mass index (BMI), glycated hemoglobin (HbA1c), diabetes duration, albumin excretion rate, triglycerides, low-density lipoprotein cholesterol (LDL-C), and statin use.

Tiglylcarnitine and methylglutarylcarnitine were independently associated with eGFR decline in the JKS validation cohort. Multivariable least absolute shrinkage and selection operator regression analysis identified six acylcarnitines independently associated with kidney function decline, including methylglutarylcarnitine, hydroxyvalerylcarnitine, and hexenoylcarnitine.

An acylcarnitine score derived from these six metabolites improved discrimination and reclassification of two clinical prediction models for kidney function decline in T2DM. The findings suggest that serum acylcarnitine profiling may help identify patients with T2DM at greater risk of progressive kidney function decline.