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Background Lipedema is a chronic adipose tissue disorder affecting primarily women and is increasingly associated with immune dysregulation and intestinal permeability. Food-specific IgG testing has been explored in various inflammatory conditions, but its relevance to lipedema remains unknown. Objective The objective of this study is to characterize IgG food sensitivity profiles in women with lipedema and investigate the paradoxical relationship between increased food reactivity and reduced total IgG antibody levels. Methods We conducted a retrospective cross-sectional study involving 234 participants: women with lipedema (n=80), women without lipedema (n=74), and men (n=80). All had undergone IgG testing against 222 food antigens via ELISA. We analyzed qualitative (positive/negative) and quantitative IgG reactivity, applied dimensionality reduction (PCA, t-SNE) and clustering, and developed a multivariable logistic regression model to assess diagnostic performance. Results Women with lipedema exhibited a non-significantly higher number of positive IgG food reactions (14.8 vs 12.6; p=0.186), despite significantly lower total IgG levels (1747.1 vs 2974.8 AU; p<0.001). This paradox was consistent across 79.7% of tested antigens. The most discriminative foods included wild game meats and certain vegetables. A combined IgG-based model achieved an area under the curve of 0.804, outperforming individual IgG metrics. Dimensionality reduction revealed no clear clustering based on reactivity patterns alone. Conclusion Lipedema displays a paradoxical IgG signature, more frequent positives despite lower total IgG, consistent with mucosal immune dysregulation (e.g., increased intestinal permeability, immune exhaustion, or dietary monotony). Single IgG metrics had limited discrimination, but a combined score improved classification, supporting IgG profiling as a complementary, not standalone, biomarker for patient stratification and personalized dietary guidance. Collectively, these findings suggest that the adipose phenotype may be downstream of broader systemic processes; prospective studies should assess IgG subclasses, barrier markers (e.g., zonulin), and gluten-modulated interventions.
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Lipedema is a chronic adipose tissue disorder traditionally considered to affect almost exclusively women, with recent estimates suggesting approximately 0.2% prevalence in men worldwide; the condition remains underdiagnosed in males due to limited awareness and scarce literature. This retrospective case series from the Amato Institute of Advanced Medicine in São Paulo, Brazil, describes clinical characteristics, diagnostic findings, and treatment outcomes of five male patients diagnosed with lipedema between January 2022 and December 2024. The patients, aged 31-58 years (mean, 42.6 ± 9.7), with a BMI of 29-42.4 kg/m², all presented bilateral, symmetrical lower extremity fat accumulation, sparing the feet, with endocrine comorbidities present in 80% of cases and one participant testing positive for HLA-DQ2/DQ8. Diagnosis was based on clinical criteria requiring bilateral symmetrical fat accumulation, disproportionate fat distribution, negative Stemmer’s sign, sparing of feet, and at least two minor criteria. Conservative management, including dietary interventions over four to eight weeks, resulted in mean weight reduction of 7.0 ± 2.2 kg and lower limb volume reduction of 2.5 ± 1.1 L. These findings demonstrate that lipedema occurs in men with classical phenotypic features, and the presence of HLA-DQ2/DQ8 markers in some cases suggests potential autoimmune components and opportunities for targeted dietary interventions. Conservative management yields significant short-term improvements, warranting larger prospective studies to establish prevalence, investigate HLA associations, and optimize management strategies for male lipedema.
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