Association of Circulating Irisin with Insulin Resistance and Metabolic Risk Markers in Prediabetic and Newly Diagnosed Type 2 Diabetes Patients

Circulating irisin, a myokine implicated in energy expenditure and adipose tissue regulation, has been increasingly studied as a potential biomarker of metabolic dysfunction. This study evaluated the relationship between serum irisin and metabolic indices, including the atherogenic index of plasma (AIP), the lipid accumulation product (LAP), and hypertriglyceridemic-waist (HTGW) phenotype in individuals with prediabetes (PreDM) and newly diagnosed type 2 diabetes mellitus (T2DM). A total of 138 participants (48 PreDM, 90 T2DM) were assessed for anthropometric, glycemic, and lipid parameters. Serum irisin levels were measured by enzyme-linked immunosorbent assay (ELISA) and correlated with insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI)), glycemic control (glycosylated hemoglobin A1c (HbA1c)), and composite lipid markers (total triglycerides-to-high-density lipoprotein cholesterol (TG/HDL-C)). Group differences were evaluated using non-parametric tests; two-way ANOVA assessed interactions between phenotypes and markers; multiple linear regression (MLR) and logistic regression models explored independent associations with metabolic indices and HTGW; receiver operating characteristic (ROC) analyses compared global and stratified model performance. Serum irisin was significantly lower in T2DM than in PreDM (median 140.4 vs. 230.7 ng/mL, <i>p</i> < 0.0001). Irisin levels remained comparable between males and females in both groups. Post hoc analysis shows that lipid indices and irisin primarily distinguish HTGW phenotypes, especially in T2DM. In both groups, irisin correlated inversely with HOMA-IR, AIP, and TG/HDL-C, and positively with QUICKI, indicating a possible compensatory role in early insulin resistance. MLR analyses revealed no independent relationship between irisin and either AIP or LAP in PreDM, while in T2DM, waist circumference remained the strongest negative predictor of irisin. Logistic regression identified age, male sex, and HbA1c as independent predictors of the HTGW phenotype, while irisin contributed modestly to overall model discrimination. ROC curves demonstrated good discriminative performance (AUC = 0.806 for global; 0.794 for PreDM; 0.813 for T2DM), suggesting comparable predictive accuracy across glycemic stages. In conclusion, irisin levels decline from prediabetes to overt diabetes and are inversely linked to lipid accumulation and insulin resistance but do not independently predict the HTGW phenotype. These findings support irisin's role as an integrative indicator of metabolic stress rather than a stand-alone biomarker. Incorporating irisin into multi-parameter metabolic panels may enhance early detection of cardiometabolic risk in dysglycemic populations.