Novel Serum FABP4 and FABP4/ Adiponectin Ratio as Predictive Biomarkers of Metabolic Risk in Type 2 Diabetes
Abstract
One important adipokine that connects adipose tissue dysfunction to metabolic issues in type 2 diabetes mellitus (T2DM) is fatty acid-binding protein 4 (FABP4). The ratio of FABP4 to adiponectin is a new integrated biomarker that shows how pro- and anti-inflammatory adipokines are balanced. Using a thorough stratified analysis across demographic and clinical subgroups, assess blood FABP4 levels and the FABP4/adiponectin ratio as predictive biomarkers for insulin resistance, systemic inflammation, and hepatic dysfunction in individuals with type 2 diabetes. Gender-stratified analysis revealed stronger correlations in females (r=0.68 vs r=0.57 in males, p=0.032). Multivariate analysis identified FABP4 /adiponectin ratio (β=0.49, 95% CI: 0.35-0.63), CRP (β=0.22, 95% CI: 0.08-0.36), and BMI (β=0.18, 95% CI: 0.05-0.31) as independent predictors of HOMA-IR (R²=0.71, p<0.001). T2DM patients exhibited significantly elevated FABP4 levels (12.5±3.2 vs. 6.8±2.1 ng/mL, p<0.001) and reduced adiponectin (7.8±2.5 vs. 11.2±3.1 μg/mL, p<0.001), resulting in a markedly higher FABP4/adiponectin ratio (1.61±0.7 vs. 0.62±0.3, p<0.001). The FABP4/adiponectin ratio demonstrated superior predictive accuracy for insulin resistance (AUC=0.87, 95% CI: 0.83-0.91) compared to FABP4 alone (AUC=0.78), adiponectin alone (AUC=0.74), or HbA1c (AUC=0.72). Gender-stratified analysis revealed stronger correlations in females (r=0.78 vs. r=0.66 in males, p=0.018) with gender-specific optimal cut-offs (>1.15 for females, >1.35 for males). Multivariate regression identified the FABP4/adiponectin ratio as the strongest independent predictors of HOMA-IR (β=0.49, 95% CI: 0.35-0.63, p<0.001), followed by CRP (β=0.22, p=0.002) and BMI (β=0.18, p=0.010), with the model explaining 74% of variance (R²=0.74, p<0.001). A clinical risk score stratified patients into low (39%), moderate (44.5%), and high risk (16.5%) categories with corresponding severe insulin resistance rates of 10%, 25%, and 60%, respectively. The FABP4/adiponectin ratio represents a robust integrated biomarker superior to traditional markers for comprehensive metabolic risk assessment in T2DM. Gender-specific variations and clear clinical cut-off values support its implementation for therapeutic monitoring and personalized treatment strategies in diabetes management.
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