Plasma Gasdermin D as a Biomarker for Pyroptosis in Early Detection of Newly Diagnosed Type 2 Diabetes Mellitus

Pyroptosis, a caspase-mediated inflammatory cell death pathway driven by Gasdermin D (GSDMD), has emerged as a potential mechanistic link between metabolic stress, β-cell injury, and chronic inflammation in Type 2 diabetes mellitus (T2DM). This study evaluated plasma GSDMD as a biomarker for newly diagnosed T2DM and explored its metabolic and inflammatory correlates. In a hospital-based case-control study, 130 newly diagnosed T2DM patients and 130 age- and sex-matched normoglycemic controls were recruited. Anthropometric indices, glycemic parameters, βFins, HOMA-IR, HOMA-β, lipid profile, and hs-CRP were measured using standard methods. Plasma GSDMD, IL-18, and IL-1β were quantified by ELISA. Group differences, correlations, multivariable logistic regression, and receiver operating characteristic (ROC) analyses were performed. T2DM patients exhibited higher BMI, adverse lipid profile, increased hs-CRP, and marked elevation of GSDMD, IL-18, and IL-1β compared with controls (all p<0.0001). Plasma GSDMD correlated positively with FBS, HbA1c, HOMA-IR, IL-18, IL-1β, and hs-CRP, and negatively with HOMA-β, indicating close links to hyperglycemia, insulin resistance, β-cell dysfunction, and systemic inflammation. In adjusted models, GSDMD remained an independent predictor of T2DM (OR 1.18 per 10 pg/mL, 95% CI 1.09-1.29), alongside IL-18, hs-CRP, higher BMI, and lower HDL-C. ROC analysis showed excellent diagnostic performance for GSDMD (AUC 0.98, 95% CI 0.96-0.99; cutoff 17.5 pg/mL; sensitivity 93.0%; specificity 97.0), superior to IL-18, IL-1β, and hs-CRP. Plasma GSDMD is markedly elevated in T2DM and integrates metabolic and inflammatory information, functioning as an independent risk factor and highly accurate diagnostic biomarker. These findings support GSDMD-mediated pyroptosis as a promising target for early diagnosis and risk stratification in T2DM.