Serum ceramide species and meteorin-like protein as a novel combined biomarker panel for the diagnosis of early-stage type 2 diabetes mellitus

Background: Early detection of biomarkers of patho-physiological changes occurring in Type 2 Diabetes Mellitus (T2DM) is crucial for timely intervention. Ceramides, a group of lipotoxic sphingolipids, and meteorin-like protein (Metrnl), a novel adipomyokine involved in insulin sensitisation, have been implicated in the pathogenesis of T2DM. This study compared the serum levels of ceramide species (Cer-16, Cer-18, Cer-24, and Cer-24:1) and Metrnl between patients with T2DM and normoglycemic controls. It assessed their diagnostic value individually and collectively. Methods: This case-control study recruited 80 patients with newly diagnosed T2DM and 80 normoglycemic controls matched for age and body mass index (BMI). Fasting blood samples were used to measure routine blood parameters. Quantification of ceramide species was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and serum Metrnl levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Patients with T2DM showed significantly increased levels of Cer-16 and Cer-18 (p<0.001 and p<0.01, respectively) and reduced levels of Cer-24 and Metrnl (p<0.001 for both). Moreover, the ratio of Cer-16 to Cer-24 was significantly increased in the T2DM group. Significant positive correlations were noted between these biomarkers and insulin resistance and glycemic control (HOMA-IR and HbA1c). However, a multivariate logistic regression model combining Cer-16, Cer-24, and Metrnl showed a significantly higher area under the ROC curve (0.93) for discriminating T2DM than did using these biomarkers individually. Conclusion: This study demonstrated for the first time that ceramide species and Metrnl levels are significantly altered in the early stages of T2DM. These changes, i.e., increased levels of Cer-16 and Cer-18 and reduced levels of Cer-24 and Metrnl, form a synergistic panel of biomarkers for the diagnosis of T2DM.

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