Associations of TNF-α, Uric Acid, and the Leptin/Adiponectin Ratio with HOMA-IR in Hospitalized Adults: A Cross-Sectional Secondary Analysis of 147 Patients

Background and Objectives: Anthropometric measures incompletely capture the inflammatory and adipokine heterogeneity underlying insulin resistance. We examined associations of tumor necrosis factor-alpha (TNF-α), serum uric acid, and the leptin/adiponectin ratio with HOMA-IR after adjustment. Materials and Methods: This single-center cross-sectional secondary analysis included 147 of 239 hospitalized adults with HOMA-IR and predefined core data; fasting glucose, insulin, and biomarker testing was elective and patient-funded. Continuous ln(HOMA-IR) was the primary outcome. A secondary upper-quartile phenotype (HOMA-IR ≥ 4.78; n = 37) was cohort-specific and non-diagnostic. Robust linear regression used HC3 standard errors. Sensitivity analyses excluded T2DM and replaced BMI with waist circumference or visceral fat area. Binary and AUC analyses were exploratory (expanded complete-case model, n = 112). Results: Each doubling of (TNF-α + 1) was associated with a 10.2% higher HOMA-IR in the expanded model (p = 0.021). The association persisted after excluding T2DM (12.1% higher HOMA-IR per doubling; n = 81; p = 0.012) and when BMI was replaced by waist circumference (p = 0.022) or visceral fat area (p = 0.018). Uric acid and the leptin/adiponectin ratio did not reach statistical significance in the adjusted continuous-outcome model. The 112 complete cases and 35 incomplete cases were broadly similar in measured baseline characteristics, although uric acid was higher among complete cases (p = 0.020). Conclusions: In this selected hospitalized cohort, TNF-α showed the most consistent adjusted association with the observed fasting glucose-insulin phenotype. The binary and discrimination analyses remain preliminary and do not establish diagnostic or clinical prediction utility. Prospective external validation is required.