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.
Amato et al. (Wed,) studied this question.