Uric acid identified through plasma metabolomics analysis may help differentiate between lipedema, lymphedema, and overweight. However, the association did not remain statistically significant following adjustment for age, body mass index (BMI), renal function, and certain drugs.
In an untargeted metabolomics analysis, researchers analyzed an exploratory cohort of 38 body mass index (BMI)-matched patients with overweight, including those with obesity, lipedema, lymphedema, and lipolymphedema. Paired citrate plasma samples underwent liquid chromatography–mass spectrometry analysis, and machine-learning methods identified uric acid as the metabolite potentially capable of differentiating the groups. The researchers then evaluated the findings in a prospective validation cohort of 198 patients treated at a high-volume lymphatic center designated as a center of excellence from the Lymphatic Education & Research Network. The validation cohort included 64 patients with lipedema, 64 patients with lymphedema, and 70 overweight controls following the exclusion of patients with a cystatin c clearance of less than 60 mL/min.
In the validation cohort, median uric acid levels were 5.1 mg/dL in the patients with lipedema, 5.4 mg/dL in those with lymphedema, and 4.6 mg/dL in controls. The researchers observed statistically significant differences between each disease group and controls, but not between lipedema and lymphedema. Receiver operating characteristic analyses showed modest discriminatory performance for uric acid alone, with area under the curve values of 0.61 for lipedema vs controls and 0.65 for lymphedema vs controls.
The researchers also evaluated a uric acid–to–cystatin c clearance ratio to account for renal function. Median ratios were 4.9 in the patients with lipedema, 5.9 in those with lymphedema, and 3.7 in controls. The ratio demonstrated improved discrimination compared with uric acid alone, with area under the curve values of 0.72 for lipedema vs controls and 0.76 for lymphedema vs controls. However, the ratio did not clearly distinguish lipedema from lymphedema.
In bootstrapped linear regression models adjusted for age, BMI, cystatin c clearance, and uric acid–lowering agents, neither uric acid nor the uric acid–to–cystatin c clearance ratio remained significantly associated with disease status. The researchers noted that uric acid has known associations with obesity, inflammation, aging, and renal dysfunction, which may have contributed to the observed differences between the groups.
The study had several limitations. Lipedema remains a clinical diagnosis without universally accepted diagnostic criteria, and the validation cohort could not be fully age- and BMI-matched because of the limited availability of healthy controls with comparable characteristics. The researchers also noted that they did not account for dietary factors or other causes of altered uric acid metabolism. In addition, the observational design limited the interpretation of causal relationships.
“While our study did find that patients with lipedema and lymphedema had higher levels of uric acid as compared to controls, this was no longer significant in our multivariable model,” wrote lead study author Fahad Alkhalfan, of the Department of Cardiovascular and Metabolic Sciences at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and colleagues.
The study authors reported no competing financial interests or personal relationships that could have influenced the work. Funding support included grants from the Lipedema Foundation, the American Heart Association, and the Doris Duke Charitable Foundation.
Source: Obesity Medicine
