OBJECTIVE: This study investigates the potential of plasma Gasdermin D (GSDMD) as a novel biomarker for early diagnosis and monitoring of type 2 diabetes mellitus. METHODS: We conducted a comparative analysis of clinical indicators among newly diagnosed diabetes patients, those with prediabetes, and healthy controls, finding significantly elevated plasma GSDMD levels in the diabetes group (P <
0.05). RESULTS: Correlation analyses revealed that GSDMD levels were positively associated with inflammatory markers and indicators of insulin resistance, while negatively correlating with HOMA-β (P <
0.001). Logistic regression analysis identified GSDMD, IL-6, and CRP as independent risk factors for type 2 diabetes (P <
0.001). The area under the ROC curve for plasma GSDMD was 0.988, indicating superior diagnostic capability compared to traditional markers like CRP (0.902) and IL-6 (0.857). With a threshold of 17.67 pg/mL, plasma GSDMD exhibited a sensitivity of 93.9% and specificity of 98.0%. CONCLUSION: These findings suggest that plasma GSDMD not only reflects early metabolic abnormalities associated with type 2 diabetes but also holds promise as a therapeutic target to mitigate inflammatory responses and improve insulin resistance. Further large-scale clinical studies are warranted to validate its diagnostic utility and enhance clinical applications.