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Background Lipedema is characterized by disproportionate gluteofemoral adiposity with anti-inflammatory properties. We hypothesized that this phenotype may confer immunological protection against T-helper 1 (Th1)-mediated autoimmunity ("Immunological Shield Hypothesis"). Objective The objective of this study is to explore whether women with a dual-energy X-ray absorptiometry (DXA)-defined lipedema-like phenotype, characterized by disproportionate gluteofemoral fat accumulation, exhibit distinct immunometabolic profiles and lower prevalence of celiac disease (CD) autoimmunity in a nationally representative sample. Methods The cross-sectional analysis included 3,833 women from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Celiac disease (n=11, 0.56% weighted prevalence) was defined by strict serology (tissue transglutaminase {tTG}-IgA+/endomysial antibody {EMA}-IgA+); lipedema phenotype was defined as leg-to-trunk fat ratio of >90th percentile via DXA. Results Women with celiac disease exhibited 7.4% lower gynoid fat (39.5% versus 42.6%, p=0.0007), persisting in overweight/obese strata. Conversely, the lipedema phenotype demonstrated superior metabolic health: 44.2% lower homeostatic model assessment of insulin resistance (HOMA-IR) (p<0.001) and 7.6% lower neutrophil-to-lymphocyte ratio (NLR) (p=0.012). Conclusions This exploratory population-based analysis identifies phenotypic divergence in fat distribution between the DXA-defined lipedema phenotype and celiac disease autoimmunity, yielding observations consistent with, but not confirmatory of, the "Immunological Shield Hypothesis." While limited by the small number of celiac cases (n=11), a sample size insufficient to detect prevalence differences for a ~7%-9% phenotype, for which approximately 225-600 celiac cases would be required, the observed differences in gynoid adiposity (7.4% reduction, p=0.0007) and the favorable metabolic profile of the lipedema phenotype (44.2% lower HOMA-IR and 7.6% lower NLR) suggest biological plausibility warranting validation in larger, targeted cohorts. These findings motivate targeted studies to evaluate whether dietary exposures, including gluten-related immune activation, interact with gluteofemoral adipose biology in lipedema.
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BACKGROUND: Lipedema is a chronic adipose tissue disorder characterized by abnormal and disproportionate fat accumulation in the extremities, leading to pain, edema, and functional impairment. Liposuction has become a central component of surgical management. However, postoperative complications, particularly seroma formation, remain a concern. OBJECTIVES: To evaluate the incidence of postoperative seroma and associated risk factors in patients undergoing liposuction for lipedema treatment, based on procedures performed by a single surgical team in a single institution. METHODS: This retrospective observational study included 93 female patients who underwent liposuction for lipedema between April 2019 and January 2024. Data collected included demographic variables, body mass index (BMI), anesthesia type, volume of aspirated fat, percentage of body weight removed, use of adjunct technologies (ultrasound or laser), association with other surgeries such as varicose vein surgery, and prior conservative treatment. The primary outcome was the development of postoperative seroma. Statistical analysis included Chi-square and Student's t-tests and multivariable logistic regression, with significance set at p ≤ 0.05. RESULTS: Among 93 cases, 17 patients (18.3%) developed postoperative seroma. Higher volumes of aspirated fat (% body weight) were significantly associated with seroma formation (7.27% vs. 5.84%, p = 0.005). Concomitant minor procedures were also linked to increased seroma incidence (p = 0.035). No seromas occurred in patients treated using ultrasound-assisted liposuction. Minor complications included one infection and one hematoma (1.07%). CONCLUSIONS: Liposuction for lipedema is a safe and effective surgical option with a low rate of major complications, but seroma remains a relatively frequent postoperative finding. Higher aspirated fat volumes relative to body weight and the presence of concomitant procedures increase the risk of seroma. No seromas were observed in the ultrasound-assisted group; however, this difference did not reach statistical significance and should be considered only as hypothesis-generating. Further studies are needed to validate these findings and guide surgical decision-making. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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