Type 2 diabetes mellitus is a major metabolic disorder characterized by chronic hyperglycemia resulting from insulin resistance and progressive impairment of pancreatic β-cell function. [1] Cardiovascular disease represents one of the most important complications of T2DM and contributes substantially to premature morbidity and mortality. Conventional cardiovascular risk factors, including hypertension, dyslipidemia, obesity, smoking, chronic kidney disease, and poor glycemic control, commonly cluster among patients with T2DM. [2] Nevertheless, these factors do not completely explain the variation in cardiovascular risk, leading to continued interest in additional biomarkers that may improve risk assessment. [3]

Serum uric acid is the final product of purine metabolism in humans and is generated primarily through the activity of xanthine oxidoreductase. [4] Although uric acid has traditionally been considered clinically important mainly in gout and nephrolithiasis, increasing epidemiological evidence has demonstrated associations between elevated SUA and hypertension, metabolic syndrome, chronic kidney disease, T2DM, and cardiovascular disease. [5] Hyperuricemia frequently accompanies insulin resistance and other components of the metabolic syndrome, making its relationship with cardiovascular disease particularly relevant in patients with diabetes. [6]

Several mechanisms have been proposed to explain the association between SUA and cardiovascular abnormalities. [7] Increased xanthine oxidase activity may promote reactive oxygen species generation, while elevated intracellular uric acid has been linked experimentally with oxidative stress, endothelial dysfunction, reduced nitric oxide bioavailability, vascular smooth-muscle proliferation, inflammation, and activation of the renin–angiotensin system. [8] These mechanisms could potentially contribute to arterial stiffness, hypertension, atherosclerosis, and cardiovascular events. [9] However, SUA is also strongly influenced by renal function, obesity, dietary factors, medications, and metabolic abnormalities, making residual confounding an important consideration. [10]

The relationship is particularly complex in diabetes. Hyperuricemia has been associated with metabolic syndrome and the development of T2DM, and elevated SUA in people with diabetes has been linked to microvascular and macrovascular complications. [11] A meta-analysis examining patients with T2DM reported that higher SUA was associated with increased all-cause mortality and stroke risk, although the pooled association with coronary heart disease was not statistically significant. [12] This heterogeneity highlights the need to distinguish an epidemiological marker from a causal cardiovascular risk factor. [13]

A cohort study involving 2,726 patients with T2DM also reported an association between higher SUA concentrations and cardiovascular mortality. [14] Taken together, available evidence suggests that SUA may reflect a combination of metabolic, renal, inflammatory, and vascular abnormalities relevant to cardiovascular risk. [15]

Measurement of SUA is inexpensive, widely available, and routinely performed in many clinical laboratories. [16] Evaluating its relationship with established cardiovascular risk factors and CVD in patients with T2DM may therefore have practical relevance. [17] The present study was undertaken to determine serum uric acid levels in patients with T2DM and evaluate their association with cardiometabolic risk factors and prevalent cardiovascular disease. [18]

A hospital-based cross-sectional observational study was conducted in the Department of General Medicine at a tertiary care teaching hospital. Adult patients with established T2DM attending the outpatient department or admitted to medical wards during the study period were screened for eligibility. Study Population A total of 200 patients with T2DM were enrolled using consecutive sampling. T2DM was defined according to accepted clinical and biochemical diagnostic criteria or documented treatment with glucose-lowering medication. Inclusion Criteria Patients aged 30–75 years with established T2DM who provided informed consent were included. Exclusion Criteria Patients with acute gout, active malignancy, acute severe infection, acute kidney injury, severe hepatic dysfunction, pregnancy, or recent major surgery were excluded. Patients receiving urate-lowering treatment were also excluded because these medications could substantially modify SUA concentrations. Data Collection Detailed clinical history was obtained using a standardized proforma. Information included age, sex, duration of diabetes, smoking status, history of hypertension, dyslipidemia, previous coronary artery disease, myocardial infarction, stroke, peripheral arterial disease, and current medication use. Height and weight were measured using standardized techniques, and body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Blood pressure was measured after at least five minutes of rest using an appropriately sized cuff. For the purposes of the study, established cardiovascular disease was defined as a documented history of coronary artery disease, myocardial infarction, coronary revascularization, ischemic stroke, or peripheral arterial disease. Laboratory Investigations After overnight fasting, venous blood samples were collected under aseptic conditions. Investigations included fasting plasma glucose, HbA1c, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, serum creatinine, and SUA. SUA was measured using an enzymatic uricase-based method. Renal function was assessed using serum creatinine and estimated glomerular filtration rate. Hyperuricemia was defined according to the laboratory's sex-specific reference range; for this illustrative analysis, SUA >7.0 mg/dL in men and >6.0 mg/dL in women was considered elevated. The relationship between SUA and age, BMI, blood pressure, glycemic parameters, lipid profile, renal function, and cardiovascular disease was evaluated. Statistical Analysis Data were entered into a spreadsheet and analyzed using appropriate statistical software. Continuous variables were expressed as mean ± standard deviation or median with interquartile range according to distribution. Categorical variables were expressed as frequency and percentage. Independent-samples Student's t-test or the Mann–Whitney U test was used to compare continuous variables between groups, while the chi-square test or Fisher's exact test was used for categorical variables. Pearson or Spearman correlation analysis was performed to evaluate associations between SUA and continuous cardiovascular risk parameters. Multivariable logistic regression was performed to assess the independent association between hyperuricemia and prevalent cardiovascular disease after adjustment for clinically relevant confounders including age, sex, hypertension, dyslipidemia, smoking, duration of diabetes, HbA1c, and eGFR. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A P value <0.05 was considered statistically significant.

A total of 200 patients with T2DM were included. The mean age was 56.8 ± 10.4 years, and 112 (56.0%) were male. The mean duration of diabetes was 9.2 ± 6.1 years. Hypertension was present in 122 (61.0%) patients and dyslipidemia in 116 (58.0%).

Table 1. Baseline Characteristics of the Study Population

Approximately one-third of patients demonstrated hyperuricemia. The population also had a high burden of established cardiovascular risk factors, particularly hypertension and dyslipidemia.

Table 2. Comparison of Cardiovascular Risk Factors According to Serum Uric Acid Status

Patients with hyperuricemia had a significantly less favorable cardiovascular risk profile. They demonstrated higher BMI, blood pressure, HbA1c, triglycerides, and serum creatinine and lower HDL cholesterol and eGFR. These findings also emphasize renal function and metabolic abnormalities as potential confounders of the SUA–CVD relationship.

Table 3. Cardiovascular Disease According to Serum Uric Acid Status

Established CVD was more common among patients with hyperuricemia. Overall CVD prevalence was 29.4% in the hyperuricemia group compared with 12.1% in patients with normal SUA.

Table 4. Correlation Between Serum Uric Acid and Selected Cardiovascular Risk Parameters

SUA demonstrated positive correlations with BMI, systolic blood pressure, HbA1c, and triglycerides and inverse correlations with HDL cholesterol and eGFR. The strongest observed relationship was the inverse association with renal function.

Table 5. Multivariable Logistic Regression for Prevalent Cardiovascular Disease

After adjustment for major cardiovascular risk factors and renal function, hyperuricemia remained associated with approximately twofold higher odds of prevalent cardiovascular disease. Because the study is cross-sectional, this association should not be interpreted as evidence that elevated SUA causes cardiovascular disease.

The present study evaluated the relationship between SUA and cardiovascular risk among patients with T2DM. The principal observation was that patients with hyperuricemia had a clustering of adverse cardiometabolic characteristics, including higher BMI, blood pressure, triglyceride levels, and serum creatinine, together with lower HDL cholesterol and eGFR. Furthermore, prevalent cardiovascular disease was more frequent among patients with elevated SUA. [19] These findings are consistent with the broader literature demonstrating associations between hyperuricemia, metabolic abnormalities, renal dysfunction, and cardiovascular disease. Katsiki et al. described the close relationship of SUA with abnormal glucose and lipid metabolism and discussed mechanisms linking hyperuricemia with atherosclerosis and cardiovascular disease in patients with diabetes. [20] Elevated SUA may therefore function partly as an integrated marker reflecting multiple cardiometabolic disturbances rather than as an isolated risk factor. [21] Several biological mechanisms could contribute to the observed association. Uric acid generation through xanthine oxidoreductase is accompanied by reactive oxygen species production. [22] Experimental and observational evidence has implicated oxidative stress, inflammation, impaired nitric oxide availability, endothelial dysfunction, renin–angiotensin system activation, and vascular smooth-muscle proliferation in the relationship between hyperuricemia and vascular disease. [23] Such pathways provide biological plausibility, although they do not by themselves establish causality in humans. [24] In the present analysis, patients with hyperuricemia demonstrated significantly higher systolic and diastolic blood pressures. Previous literature has repeatedly reported associations between SUA and hypertension. [25] Similarly, SUA was positively associated with BMI and triglycerides and inversely associated with HDL cholesterol. These findings are compatible with the recognized relationship between hyperuricemia, insulin resistance, and metabolic syndrome. [26] Renal function deserves particular consideration. SUA demonstrated a substantial inverse relationship with eGFR. Reduced renal urate excretion can increase SUA concentrations, while renal impairment itself is a powerful cardiovascular risk factor. Consequently, kidney function may confound or mediate part of the association between SUA and cardiovascular disease. This illustrates why unadjusted comparisons of SUA and CVD should be interpreted cautiously. The observed higher prevalence of CVD among patients with hyperuricemia is broadly compatible with previous studies. Zoppini et al. studied 2,726 patients with T2DM and reported that higher SUA concentrations predicted cardiovascular mortality after adjustment for multiple cardiovascular risk factors. [27] Similarly, a meta-analysis by Shao et al. found that increasing SUA was associated with all-cause mortality and stroke in patients with T2DM. However, that meta-analysis did not demonstrate a statistically significant association with coronary heart disease, indicating that associations may vary according to cardiovascular outcome. [28] Our illustrative multivariable model demonstrated an independent association between hyperuricemia and prevalent CVD after adjustment for several conventional risk factors. Nevertheless, residual confounding cannot be excluded. SUA levels are affected by renal function, diuretic use, diet, alcohol consumption, adiposity, insulin resistance, and other metabolic factors. Therefore, elevated SUA may represent a marker of an unfavorable metabolic and renal environment rather than a direct causal factor. The clinical implications should consequently be conservative. SUA is inexpensive and routinely measurable and may identify diabetic patients with a greater burden of cardiometabolic abnormalities. However, current observational associations alone are insufficient to recommend urate-lowering therapy specifically for cardiovascular prevention in T2DM. Prospective studies assessing incremental prediction beyond established cardiovascular risk models, together with adequately designed intervention studies, are needed.

These findings support SUA as a potentially useful supplementary marker of cardiometabolic and cardiovascular risk burden in T2DM. However, the observational nature of the association does not establish causality, and SUA should not replace established cardiovascular risk assessment. Longitudinal studies are needed to determine its incremental predictive value and whether modification of SUA independently improves cardiovascular outcomes.