Insulin resistance is a metabolic condition in which target tissues such as skeletal muscle, adipose tissue, and liver exhibit a diminished response to insulin action. It is recognized as a central feature of type 2 diabetes mellitus (T2DM), metabolic syndrome, obesity, and cardiovascular disease (1). The increasing prevalence of insulin resistance worldwide has become a major public health concern because of its association with significant morbidity and mortality (2).

In recent years, serum uric acid (SUA), the final product of purine metabolism in humans, has attracted considerable attention as a potential contributor to metabolic disorders. Traditionally, hyperuricemia has been associated with gout and renal disease. However, growing evidence suggests that elevated SUA levels may also play a role in the pathogenesis of insulin resistance, hypertension, obesity, metabolic syndrome, and cardiovascular disease (3).

Uric acid is produced by the action of xanthine oxidase during purine degradation. Although uric acid functions as an antioxidant in extracellular environments, elevated intracellular uric acid may induce oxidative stress, inflammation, and endothelial dysfunction (4). Experimental studies have demonstrated that increased uric acid levels reduce nitric oxide bioavailability, impair insulin-mediated glucose uptake, and promote vascular smooth muscle proliferation (5).

Several epidemiological studies have reported a positive association between serum uric acid and insulin resistance. Hyperuricemia is frequently observed in individuals with obesity and metabolic syndrome, conditions characterized by impaired insulin sensitivity (6). Insulin resistance itself may contribute to hyperuricemia by reducing renal uric acid excretion, resulting in a bidirectional relationship between the two conditions (7).

The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is a widely accepted method for estimating insulin resistance using fasting plasma glucose and fasting insulin concentrations (8). Elevated HOMA-IR values have been associated with increased risk of diabetes, cardiovascular disease, and metabolic syndrome. Several studies have demonstrated significant correlations between SUA and HOMA-IR, suggesting that uric acid may serve as a marker of metabolic dysfunction (9,10).

The biological mechanisms linking uric acid and insulin resistance are multifactorial. Increased uric acid levels stimulate oxidative stress and inflammatory pathways, including activation of nuclear factor-kappa B (NF-κB) and production of pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 (11). These inflammatory mediators interfere with insulin signaling pathways and contribute to the development of insulin resistance (12).

Given the increasing prevalence of both hyperuricemia and insulin resistance, understanding their relationship may have important clinical implications. Early identification of individuals with elevated SUA may facilitate preventive interventions aimed at reducing the risk of diabetes and cardiovascular disease.

Therefore, the present study was undertaken to evaluate the association between serum uric acid and insulin resistance among adults and to determine the relationship between SUA and various metabolic parameters.

A hospital-based cross-sectional analytical study was conducted in the Department of Biochemistry in collaboration with the Department of General Medicine at a tertiary care teaching hospital over a period of six months. Study Population The study included 150 adults aged between 25 and 60 years attending the outpatient department for routine health evaluation. Inclusion Criteria • Adults aged 25–60 years. • Both males and females. • Willingness to provide informed consent. Exclusion Criteria • Diagnosed diabetes mellitus on insulin therapy. • Chronic kidney disease. • Gout. • Liver disease. • Pregnancy. • Malignancy. • Acute infections or inflammatory disorders. • Use of uric acid-lowering medications. Ethical Approval The study protocol was approved by the Institutional Ethics Committee. Written informed consent was obtained from all participants before enrollment. Data Collection A detailed medical history was obtained. Information regarding age, gender, dietary habits, smoking status, alcohol consumption, physical activity, and family history of diabetes was recorded. Anthropometric Measurements The following parameters were measured: • Height (cm) • Weight (kg) • Body Mass Index (BMI) • Waist circumference (cm) • Blood pressure (mmHg) Blood Sample Collection After an overnight fast of 10–12 hours, 5 mL of venous blood was collected under aseptic conditions. Laboratory Investigations Serum Uric Acid Serum uric acid was measured using the enzymatic uricase-peroxidase method on an automated biochemistry analyzer. Fasting Plasma Glucose Estimated by glucose oxidase-peroxidase method. Fasting Serum Insulin Measured using chemiluminescence immunoassay. Lipid Profile Included: • Total cholesterol • Triglycerides • HDL cholesterol • LDL cholesterol Assessment of Insulin Resistance Insulin resistance was calculated using HOMA-IR: HOMA-IR = Fasting Insulin (µIU/mL) × Fasting Glucose (mg/dL) / 405 Grouping of Participants Participants were divided into three tertiles based on SUA levels: • Tertile I: <4.5 mg/dL • Tertile II: 4.5–6.0 mg/dL • Tertile III: >6.0 mg/dL Statistical Analysis Data were analyzed using SPSS version 25. • Mean ± SD for continuous variables. • One-way ANOVA for group comparisons. • Pearson correlation coefficient for associations. • Multiple linear regression analysis to identify independent predictors of HOMA-IR. A p-value <0.05 was considered statistically significant.

Table 1. Baseline Characteristics According to Serum Uric Acid Tertiles

Participants with higher serum uric acid levels had significantly greater BMI and waist circumference, suggesting an association between hyperuricemia and obesity-related parameters.

Table 2. Metabolic Parameters Across Serum Uric Acid Tertiles

Insulin resistance and triglyceride levels increased significantly with rising serum uric acid concentrations.

Table 3. Correlation of Serum Uric Acid with Metabolic Variables

Serum uric acid demonstrated significant positive correlations with obesity indices and insulin resistance markers, with the strongest association observed for HOMA-IR.

The present study evaluated the association between serum uric acid and insulin resistance among adults and demonstrated a significant positive relationship between SUA and HOMA-IR. Participants with elevated uric acid levels exhibited higher fasting insulin concentrations, greater insulin resistance, and adverse metabolic profiles. Hyperuricemia has emerged as an important metabolic risk factor beyond its traditional association with gout. Several epidemiological studies have demonstrated that elevated SUA levels are strongly linked with obesity, metabolic syndrome, hypertension, and type 2 diabetes mellitus (3,6). The findings of the present study are consistent with previous reports showing a significant positive correlation between SUA and insulin resistance indices (9,10). One of the principal findings of this study was the progressive increase in HOMA-IR values across increasing uric acid tertiles. Similar observations were reported by Quinones Galvan et al., who demonstrated that hyperuricemic individuals had significantly reduced insulin sensitivity compared with normouricemic controls (13). Elevated insulin levels may decrease renal excretion of uric acid, thereby contributing to hyperuricemia. The mechanisms linking uric acid and insulin resistance are complex. Experimental studies suggest that intracellular uric acid promotes oxidative stress through activation of nicotinamide adenine dinucleotide phosphate oxidase and generation of reactive oxygen species (14). Increased oxidative stress impairs insulin signaling pathways and contributes to metabolic dysfunction. Another important mechanism involves endothelial dysfunction. Nitric oxide plays a critical role in insulin-mediated glucose uptake by facilitating blood flow to skeletal muscle tissues. Elevated uric acid reduces nitric oxide bioavailability and impairs endothelial function, thereby contributing to insulin resistance (5). The present study also observed significant positive correlations between SUA and BMI as well as waist circumference. Obesity is associated with increased uric acid production and decreased renal excretion. Adipose tissue-derived inflammatory cytokines may further contribute to insulin resistance and hyperuricemia (15). Triglyceride levels were significantly higher among individuals with elevated SUA levels. Similar findings have been reported in previous studies where hyperuricemia was associated with dyslipidemia and increased cardiovascular risk (16). These observations suggest that uric acid may represent an integrated marker of metabolic dysfunction. The clinical significance of these findings lies in the potential use of SUA as a simple, inexpensive, and widely available biomarker for identifying individuals at risk of insulin resistance. Early detection may facilitate lifestyle modifications and preventive interventions aimed at reducing the burden of diabetes and cardiovascular disease. The strengths of this study include comprehensive metabolic assessment and standardized laboratory methods. However, certain limitations should be acknowledged. The cross-sectional design limits causal inference, and the sample size was relatively modest. Longitudinal studies are required to determine whether reduction of uric acid levels improves insulin sensitivity. Overall, the findings support the growing evidence that elevated serum uric acid is closely associated with insulin resistance and adverse metabolic outcomes.

Serum uric acid levels demonstrated a significant positive association with insulin resistance as assessed by HOMA-IR. Higher uric acid concentrations were associated with increased fasting insulin levels, obesity indices, and triglyceride concentrations. These findings suggest that serum uric acid may serve as an important biochemical marker for identifying individuals at increased risk of metabolic syndrome, insulin resistance, and future type 2 diabetes mellitus.

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