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 (ageadjusted
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.