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We conducted a comparative study involving 39 female patients with lipedema and group-matched controls at a ratio of 1:5. The primary survey tool was the German Health Update (GEDA 2019/2020-EHIS) questionnaire, which was developed by the Robert Koch Institute (RKI), Germany. The secondary survey tool was the German Pain Questionnaire. The prevalence of hypertension (p = 0.041) and high blood lipids (p = 0.024) was lower in the lipedema group compared to the control group. General health and well-being indicators demonstrated lower overall health ratings (p < 0.001) and higher physiotherapy use in patients with lipedema (p = 0.016). Mental health assessment revealed higher depression prevalence and severity (p = 0.001), together with a lower number of close contacts (p = 0.032). Furthermore, patients with lipedema experienced higher levels of pain (p < 0.001) and more significant pain-related disability in daily activities (p < 0.001) than controls. Correlation analysis among patients with lipedema showed a positive correlation between pain severity and depressive symptoms (ρ = 0.612, p < 0.001) and a moderate positive correlation with impaired health-related quality of life (ρ = 0.418, p = 0.010). In summary, our findings highlight significant differences in health and well-being between patients with lipedema and matched controls, especially in overall, metabolic, and mental health, as well as pain perception. The findings emphasize the need for a validated lipedema-specific questionnaire and a multidisciplinary treatment approach with a combination of physical therapies, lifestyle adjustments, and psychological strategies.
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Lipedema is a chronic condition characterized by disproportionate and symmetrical enlargement of adipose tissue, predominantly affecting the lower limbs of women. This study investigated the use of metabolomics in lipedema research, with the objective of identifying complex metabolic disturbances and potential biomarkers for early detection, prognosis, and treatment strategies. The study group (n = 25) comprised women diagnosed with lipedema. The controls were 25 lean women and 25 obese females, both matched for age. In the patients with lipedema, there were notable changes in the metabolite parameters. Specifically, lower levels of histidine and phenylalanine were observed, whereas pyruvic acid was elevated compared with the weight controls. The receiver operating characteristic (ROC) curves for the diagnostic accuracy of histidine, phenylalanine, and pyruvic acid concentrations in distinguishing between patients with lipedema and those with obesity but without lipedema revealed good diagnostic ability for all parameters, with pyruvic acid being the most promising (area under the curve (AUC): 0.9992). Subgroup analysis within matched body mass index (BMI) ranges (30.0 to 39.9 kg/m2) further revealed that differences in pyruvic acid, phenylalanine, and histidine levels are likely linked to lipedema pathology rather than BMI variations. Changes in low-density lipoprotein (LDL)-6 TG levels and significant reductions in various LDL-2-carried lipids of patients with lipedema, compared with the lean controls, were observed. However, these lipids were similar between the lipedema patients and the obese controls, suggesting that these alterations are related to adiposity. Metabolomics is a valuable tool for investigating lipedema, offering a comprehensive view of metabolic changes and insights into lipedema's underlying mechanisms.
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Background: Lipedema is a chronic adipose tissue disorder with disproportionate fat accumulation in the extremities and is often misdiagnosed as obesity. Although women with lipedema appear to be metabolically distinct from body mass index (BMI)-matched controls, their fasting metabolism remains insufficiently characterized. We therefore aimed to define the metabolic signature of lipedema using serum NMR metabolomics and anthropometric profiling. Methods: We conducted a study with 24 premenopausal women with lipedema and 21 BMI-matched controls. Fasting serum samples were analyzed using NMR spectroscopy and anthropometric data were collected. Regional body composition was additionally assessed in an exploratory matched DXA subset (n=12). To characterize coordinated metabolic differences beyond single analytes, we derived exploratory composite indices and applied multivariate analyses. Results: Despite similar BMI, women with lipedema showed lower waist circumference, waist-to-hip ratio and lower fasting insulin than controls (age-adjusted p=0.032). NMR profiling revealed lower alanine (p<0.001), lactate (p=0.004), pyruvate (p=0.021), and elevated ketone bodies (3-hydroxybutyric acid: p=0.009; acetoacetic acid: p=0.035; acetone: p=0.006). These alterations were reflected by significant group differences in composite indices for fat distribution (g=1.26; p<0.001), glycolysis (g=0.74; p=0.018), and ketone metabolism (g=0.70; p=0.018). Principal component analysis of the selected indices explained 78% of the total variance and showed partial group separation between lipedema and controls. Conclusion: Lipedema is associated with a distinct fasting metabolic profile characterized by reduced glycolytic intermediates, enhanced ketone body signals, and a more peripheral fat distribution despite comparable BMI. These findings support the concept of lipedema as a metabolically distinct phenotype and suggest that multivariate metabolic signatures may help refine future diagnostic and interventional approaches.
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