BackgroundAcylcarnitines play a role in type 2 diabetes mellitus (T2DM), but the relationship between acylcarnitine and diabetic nephropathy was unclear. We aimed to explore the association of acylcarnitine metabolites with diabetic nephropathy and estimate the predictive value of acylcarnitine for diabetic nephropathy.MethodsA total of 1032 (mean age: 57.24 ± 13.82) T2DM participants were derived from Liaoning Medical University First Affiliated Hospital. Mass Spectrometry was utilized to measure levels of 25 acylcarnitine metabolites in fasting plasma. Diabetic nephropathy was ascertained based on the medical records. Factor analysis was used to reduce the dimensions and extract factors of the 25 acylcarnitine metabolites. Logistic regression was used to estimate the relationship between factors extracted from the 25 acylcarnitine metabolites and diabetic nephropathy. Receiver operating characteristic curves were used to test the predictive values of acylcarnitine factors for diabetic nephropathy.ResultsAmong all T2DM participants, 138 (13.37%) patients had diabetic nephropathy. Six factors were extracted from 25 acylcarnitines, which account for 69.42% of the total variance. In multi-adjusted logistic regression models, the odds ratio (OR, 95% confidence interval [CI]) of diabetic nephropathy on factor 1 (including butyrylcarnitine/glutaryl-carnitine/hexanoylcarnitine/octanoylcarnitine/decanoylcarnitine/lauroylcarnitine/tetradecenoylcarnitine), factor 2 (including propionylcarnitine/palmitoylcarnitine/hydroxypalmitoleyl-carnitine/octadecanoylcarnitine/arachidiccarnitine), and factor 3 (including tetradecanoyldiacylcarnitine/behenic carnitine/tetracosanoic carnitine/hexacosanoic carnitine) were 1.33 (95%CI 1.12–1.58), 0.76 (95%CI 0.62–0.93), and 1.24 (95%CI 1.05–1.47), respectively. The area under the curve for diabetic nephropathy prediction was significantly increased after the complement of factors 1, 2, and 3 in traditional factors model (P< 0.01).ConclusionsSome plasma acylcarnitine metabolites extracted in factors 1 and 3 were higher in diabetic nephropathy, while factor 2 was lower in diabetic nephropathy among T2DM patients. The addition of acylcarnitine to traditional factors model improved the predictive value for diabetic nephropathy.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13098-023-01058-1.