Abstract
Background: Insulin resistance (IR) is a complex metabolic disorder characterized by impaired cellular response to insulin, lipotoxicity, and chronic inflammation. Fetuin-A, a hepatokine secreted by the liver.
Methods: This case-control study was conducted at the National Diabetic Center from march 2026 to septemper 2026, involving 180 male participants aged 18-65 years. The study included 120 newly diagnosed (not yet on anti-diabetic treatment) dysglycemia (prediabetes or diabetes) and insulin resistance, and 60 apparently healthy controls matched for age, gender, and BMI. Serum fetuin-A levels were measured using sandwich ELISA.
Results: Patients showed significantly elevated fetuin-A levels compared to controls (median: 40.46 vs. 8.40 ng/ml, P<0.0001), representing a more than 4-fold increase. HbA1c (median: 6.400% vs. 4.85%, P<0.0001) and HOMA-IR (median: 4.90 vs. 1.65, P<0.0001) were also significantly higher in patients. Fetuin-A demonstrated strong positive correlations with HOMA-IR (r=0.763, P<0.0001) and HbA1c (r=0.670, P<0.0001). ROC analysis revealed excellent diagnostic performance with an AUC of 0.974 (95% CI: 0.938-0.992), sensitivity of 90.00%, and specificity of 96.67% at a cut-off value of >29.543 ng/ml. Subgroup analysis showed that fetuin-A was significantly elevated in both diabetic (median: 40.68ng/ml) and prediabetic (median: 40.40 ng/ml) groups compared to normoglycemic individuals (median: 9.62 ng/ml, P<0.0001), with no significant difference between diabetic and prediabetic groups. Similarly, fetuin-A levels were comparable between borderline (median: 39.50 ng/ml) and insulin-resistant (median: 40.52 ng/ml) HOMA-IR categories, indicating early elevation. Univariate logistic regression identified fetuin-A as a strong independent predictor of patient status (OR=1.22, P<0.0001, AUC=0.974), with each 1ng/ml increase associated with a 22% increase in the odds of being a patient.
Conclusion: Fetuin-A is significantly elevated in prediabetic patients with insulin resistance and demonstrates excellent diagnostic accuracy as a biomarker. Its early elevation in prediabetes and borderline insulin resistance suggests that fetuin-A may serve as an early warning biomarker for identifying individuals at risk of progressing to type 2 diabetes, before conventional glycemic markers become abnormal. These findings support the role of fetuin-A as a key hepatokine linking hepatic metabolic dysfunction to peripheral insulin resistance and highlight its potential clinical utility in early risk stratification and intervention, these findings are limited by the case-control design, male-only enrollment, and lack of adjustment for hepatic steatosis and lifestyle confounders; validation in prospective, mixed-sex cohorts is required.
| Intend to be published in the IJPS ? | NO |
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| Has the manuscript been published | not published |
