Abstract
Background: The identification of biomarkers reflecting early pathophysiological changes in Type 2 Diabetes Mellitus (T2DM) is crucial for timely intervention. Ceramides, lipotoxic sphingolipids, and Meteorin-like protein (Metrnl), an insulin-sensitizing adipomyokine, are mechanistically linked to T2DM development.
Aims: To compare serum levels of specific ceramides (Cer-16, Cer-18, Cer-24, Cer-24:1) and Metrnl between T2DM patients and controls, and to evaluate their individual and combined diagnostic accuracy.
Methods: This case-control study included 80 newly diagnosed T2DM patients and 80 age- and BMI-matched normoglycemic controls. Fasting serum was analysed for standard biochemical parameters. Ceramide species were quantified by LC-MS/MS. Serum Metrnl was measured via ELISA.
Results: The T2DM group exhibited significantly elevated levels of Cer-16 (p<0.001) and Cer-18 (p<0.01), and reduced levels of Cer-24 and Metrnl (both p<0.001). The Cer-16/Cer-24 ratio was significantly higher in T2DM. Strong correlations were found between these biomarkers and HOMA-IR/HbA1c. A multivariate logistic regression model combining Cer-16, Cer-24, and Metrnl yielded an AUC of 0.93 for T2DM discrimination, superior to any single marker.
Conclusions: A distinct ceramide profile (high Cer-16, low Cer-24) coupled with low Metrnl characterizes early T2DM. Their combination forms a synergistic biomarker panel with high diagnostic potential, mirroring the dual pathology of lipotoxicity and impaired metabolic protection.
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