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Lipedema and lymphedema are physically similar yet distinct diseases that are commonly misdiagnosed. We previously reported that lipedema and lymphedema are associated with increased risk for venous thromboembolism (VTE). The underlying etiology of the prothrombotic profile observed in lipedema and lymphedema is unclear, but may be related to alterations in platelets. Our objective was to analyze the platelet transcriptome to identify biological pathways that may provide insight into platelet activation and thrombosis. The platelet transcriptome was evaluated in patients with lymphedema and lipedema, then compared to control subjects with obesity. Patients with lipedema were found to have a divergent transcriptome from patients with lymphedema. The platelet transcriptome and impacted biological pathways in lipedema were surprisingly similar to weight-matched comparators, yet different when compared to overweight individuals with a lower body mass index (BMI). Differences in the platelet transcriptome for patients with lipedema and lymphedema were found in biological pathways required for protein synthesis and degradation, as well as metabolism. Key differences in the platelet transcriptome for patients with lipedema compared to BMI-matched subjects involved metabolism and glycosaminoglycan processing. These inherent differences in the platelet transcriptome warrant further investigation, and may contribute to the increased risk of thrombosis in patients with lipedema and lymphedema.
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Aims Lipedema is a condition often mistaken for other causes of limb swelling including lymphedema and obesity. Lipedema may have a unique metabolic profile. Interrogation of the metabolome is a strategy that could reveal unique biomarkers to distinguish lipedema from lymphedema and obesity. Methods Unbiased metabolomics was utilized to examine 38 BMI-matched overweight patients compared with patients with lipedema, lymphedema, and lipolymphedema. Machine learning identified biomarkers to distinguish diseases, and further examined in a validation cohort of 198 patients with each disorders. Adjustments were made for baseline clinical and demographic variables. Results Plasma metabolomics firstly revealed uric acid as a biomarker that performs well to distinguish between phenotypically similar diseases in patients with elevated BMI. In a validation cohort of 64 patients with lipedema, uric acid (5.05 mg/dL) was compared with 64 patients with lymphedema (5.4 mg/dl), and 70 overweight patients without these conditions (4.6 mg/dL, p<0.05). Uric acid-to-cystatin c ratio distinguished between all three groups (Lipedema: 5.2; Lymphedema: 6.3; overweight: 4.0, p<0.01); however, significance was lost after adjustment for renal function. Conclusion Metabolomic analysis revealed uric acid may differentiate between lipedema, lymphedema, lipolymphedema and obese individuals without those conditions. In a validation cohort, while uric acid was higher in lipedema and lymphedema, uric acid adjusted by cystatin c clearance revealed uric acid to be a less useful marker to distinguish lipedema from lymphedema in the context of renal insufficiency.
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Topic
- Lipedema
- LF Funded (2)
- Open Access (1)
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- Journal Article (2)
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