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I found the recent study by Alkhalfan et al. for identifying uric acid as a potential biomarker for lipedema and lymphedema through untargeted plasma metabolomics. To further enhance the clinical translation of these findings, I, propose a structured framework comprising baseline control characterization, longitudinal uric acid profiling across treatment phases, multi-analyte biomarker integration, and endocrine-based stratification. This approach aims to improve diagnostic specificity, accommodate inter-individual variability, and establish uric acid as a reliable tool in differentiating and monitoring lymphatic disorders.

Objectives This double-blind, randomized clinical trial sought to demonstrate the effectiveness of Pycnogenol® in the symptomatic control and body composition management of patients with lipedema. Methods This was a double-blind, randomized clinical trial with 60 days of follow-up involving one hundred patients. The study utilized a quality-of-life questionnaire (QuASiL), bioimpedance analysis, and clinical monitoring. Results Of the one hundred patients initially included, seven were lost to follow-up; however, monotonic multiple imputation was applied for data analysis. The two groups were similar in all aspects except for initial weight. The placebo group showed an increase in mean QuASiL scores after 30 and 60 days from the first assessment, representing a worsening of symptoms over time. In contrast, the intervention group demonstrated a progressive and significant reduction in scores, with means of 69.5 ± 28 at 30 days and 63.2 ± 27 at 60 days (p < 0.001). This group also showed a statistically significant reduction in weight, BMI, and body fat percentage. Conclusions Pycnogenol® appears to be a promising therapeutic option to support the clinical management of lipedema, a condition that exerts numerous negative physical and emotional impacts throughout the lives of affected patients.

Lipedema is a chronic disorder characterized by the symmetrical accumulation of subcutaneous adipose tissue, predominantly affecting women. Despite increasing recognition, the pathophysiological mechanisms underlying adipose tissue dysfunction in lipedema remain incompletely understood. This mini review combines current knowledge about adipose tissue biology in lipedema, highlighting recent discoveries, ongoing controversies, and future research directions. A comprehensive literature review was conducted focusing on adipose tissue-related research in lipedema with emphasis on pathophysiological mechanisms, cellular composition, and therapeutic implications. Recent studies reveal that lipedema adipose tissue exhibits distinct characteristics, including M2 macrophage predominance, stage-dependent adipocyte hypertrophy, progressive fibrosis, and altered lymphatic/vascular function. The inflammatory profile differs markedly from obesity, with an anti-inflammatory M2-like macrophage phenotype rather than the pro-inflammatory M1 response seen in classic obesity. Emerging evidence suggests lipedema may represent a model of “healthy” subcutaneous adipose tissue expansion with preserved metabolic function despite increased adiposity. Current research proposes menopause as a critical turning point, driven by estrogen receptor imbalance and intracrine estrogen excess. Lipedema represents a unique adipose tissue disorder distinct from obesity, characterized by specific cellular and molecular signatures. Current research gaps include the need for validated biomarkers, standardized diagnostic criteria, and targeted therapeutics. Future research should focus on elucidating the molecular mechanisms driving adipose tissue dysfunction and developing precision medicine approaches.

BACKGROUND: Lipedema is a chronic adipose tissue disorder characterized by abnormal fat accumulation, pain, often necessitating surgical intervention. While liposuction is the primary treatment to remove pathological fat, postoperative skin laxity poses a significant challenge, particularly in advanced stages. OBJECTIVE: This study evaluates the efficacy of helium plasma technology as an adjunct to liposuction of the lower limbs across the three clinical stages of lipedema, with a focus on its impact on skin tone, elasticity, and the necessity for dermolipectomy. METHODS: A prospective study was conducted on 90 female patients with lower limbs lipedema, divided equally across Stages I, II, and III. Helium plasma technology was applied post-liposuction to enhance skin tightening. Outcomes included postoperative skin elasticity, dermolipectomy incidence, and patient satisfaction RESULTS: In Stage I, skin tone and elasticity increased by 25%, though the already low need for dermolipectomy remained largely unchanged. In Stage II, skin elasticity improved by 40%, reducing the incidence of dermolipectomy from 30 to 10%. In Stage III, while the need for dermolipectomy was unaffected, helium plasma contributed to improved skin elasticity and patient satisfaction. No major adverse events were reported. This study is limited by the absence of a randomized control group and the lack of blinding in outcome assessments, which may introduce observer bias. These factors should be considered when interpreting the results and highlight the need for future controlled trials. CONCLUSIONS: Helium plasma technology offers stage-specific benefits in liposuction for lipedema of the lower limbs. It enhances skin tone and elasticity in early stages, reduces dermolipectomy requirements in intermediate stages, and improves skin quality in advanced stages when combined with dermolipectomy. Further research is needed to validate these findings and optimize protocols for clinical use. 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 .

Lipedema is a chronic, progressive adipose tissue disorder that affects up to 10% of women and is characterized by disproportionate lower-limb fat accumulation, pain, edema, and resistance to conventional weight-loss approaches. Its pathophysiology involves a complex interplay of adipocyte hypertrophy, chronic inflammation, extracellular matrix fibrosis, mitochondrial dysfunction, and sex steroid imbalance, highlighting the need for disease-modifying therapies. This narrative review synthesizes mechanistic, translational, and clinical evidence linking metabolic, inflammatory, and fibrotic pathways to lipedema and tirzepatide's potential therapeutic relevance. Tirzepatide, a dual GLP-1 (Glucagon-Like Peptide-1)/GIP (Glucose-Dependent Insulinotropic Polypeptide) receptor agonist, has demonstrated unprecedented efficacy in obesity and diabetes, alongside pleiotropic actions on inflammation, fibrosis, and adipose remodeling. Mechanistic studies reveal favorable effects on macrophage polarization, cytokine signaling, extracellular matrix turnover, and thermogenesis, suggesting potential relevance to lipedema biology. Translational evidence from related fibro-inflammatory conditions such as steatohepatitis and heart failure further supports its antifibrotic and immunomodulatory plausibility. Although direct clinical evidence in lipedema is lacking, the convergence of mechanistic pathways provides a strong rationale to investigate tirzepatide as a disease-modifying candidate. If future clinical studies confirm these mechanisms, tirzepatide could represent a novel metabolic-hormonal therapy capable of modifying the natural course of lipedema.

Background/Objectives: Lipedema is a chronic disorder characterized by disproportionate fat accumulation in the extremities, causing pain, bruising, and reduced mobility. When conservative therapy fails, liposuction is considered an effective treatment option. Prior studies often relied on subjective or non-standardized measures, limiting precision. This study aimed to objectively assess volumetric changes after liposuction in stage III lipedema using high-resolution 3D imaging to quantify postoperative changes in circumference and volume, providing individualized yet standardized outcome measures aligned with precision medicine. Methods: We retrospectively analyzed 66 patients who underwent 161 water-assisted liposuctions (WALs). Pre- and postoperative measurements were performed with the VECTRA© WB360 system, allowing reproducible, anatomically specific quantification of limb volumes and circumferences. Secondary endpoints included in-hospital complications. Results: Liposuction achieved significant reductions in all treated regions, most pronounced in the proximal thigh and upper arm. Thigh volume decreased by 4.10–9.25% (q < 0.001), while upper arm volume decreased by 15.63% (left) and 20.15% (right) (q = 0.001). Circumference decreased by up to 5.2% in the thigh (q < 0.001) and 12.27% (q = 0.001) in the upper arm. All changes were calculated relative to baseline values, allowing personalized interpretation of treatment effects. Conclusions: This is the first study to objectively quantify postoperative lipedema changes using whole-body 3D surface imaging. By capturing each patient’s contours pre- and postoperatively, this approach enables individualized evaluation while permitting standardized comparison across patients. It offers a precise understanding of surgical outcomes and supports integration of precision medicine principles in lipedema surgery.

Lipedema is a chronic and potentially progressive fat distribution disorder. Disease-related symptoms, such as pain and discomfort, can require surgical intervention when conservative therapies are exhausted. These megaliposuctions are functional in nature and need to be distinguished from esthetic liposuctions. This new surgical approach, the hybrid technique combining power-assisted liposuction (PAL) with manual extraction (ME), has been developed to more effectively treat fibrotic nodules, particularly in the lower legs, where conventional liposuction techniques often fall short.

Knee pain in women with lipedema is frequently misattributed and undertreated. We outline a biomechanical and inflammatory cascade linking systemic adipose dysfunction, anabolic resistance, and thigh-predominant sarcopenia to dynamic knee valgus, plantar arch collapse, altered gait, patellofemoral malalignment, and ultimately chondromalacia patellae. We integrate synovial-adipose crosstalk and the high prevalence of generalized joint hypermobility as amplifiers of joint loading. This framework supports a practical, staged approach that couples symptom control with progressive, targeted strengthening and gait retraining. Rather than treating the knee in isolation, addressing the cascade may reduce pain and improve function.

Lipedema is a clinical entity that deserves special attention, as it predominantly affects women during specific hormonal phases such as menarche, pregnancy and menopause. Among the available treatments, surgery is considered the most invasive and is usually indicated for severe cases. As an alternative, conservative therapies may be recommended, including photobiomodulation therapy (PBMT), which still requires scientific substantiation to validate its effectiveness. We conducted a clinical study involving three patients who underwent dermolipectomy for previously indicated medical reasons. Prior to surgery, PBMT was applied using red and infrared LED irradiation on one side of the body, with the contralateral side serving as a non-irradiated control. PBMT was administered 3–4 h before the surgical procedure. The excised skin samples from both treated and control sites were subjected to histopathological analysis. Qualitative assessments (H&E staining) and adipocyte histomorphometry were performed, alongside immunohistochemistry using the following markers: caspase-3 (apoptosis), CD68 (macrophages), COX-2 and Cytochome P4501A1 (CYP1A1). Results demonstrate positive effects, including a reduced adipocyte size in irradiated sites modulation of inflammatory process and increasing COX-2 and macrophage activity in this early post-treatment phase, enhanced adipocyte apoptosis, and upregulation of aromatase (CYP1A1). These membrane-associated hemoproteins are known to catalyze mono-oxygenation of both endogenous and exogenous substrates such as hormones, fatty acids. This is the first study to investigate the effects of PBMT in lipedema patients. Despite is preliminary nature, the findings suggest that PBMT exerts beneficial biological effects on lipedema tissue when applied under the tested parameters.

This article aims to summarize contemporary understanding and management strategies of lipedema. It will elucidate recent advancements in diagnostic methodologies, the role of imaging technologies, and evolving therapeutic interventions. The article will further delineate critical areas that warrant further investigation.

Background: We aimed to assess the sleep quality and the relationship between sleep and fatigue and quality of life in female lipedema patients.Methods and Results: A total of 52 patients with lipedema (Group 1) and 40 healthy control subjects (Group 2) were enrolled. The type and stage of lipedema were recorded for Group 1. The quality of sleep was assessed by using the Pittsburgh Sleep Quality Index (PSQI). The Fatigue Severity Scale (FSS) was used for assessing fatigue. Quality of life was assessed with the World Health Organization Quality of Life. The mean age of the patient group was 45.26 ± 9.81, whereas it was 42.10 ± 6.36 years in the control group (p > 0.05). The mean body mass index was 30.23 ± 4.70 in Group 1 and 28.55 ± 4.14 in Group 2 (p > 0.05). The total PSQI score was 10 (range: 7–12.75) in Group 1 and 8 (range: 5–10) in Group 2 (p < 0.05). There was no difference between the groups in terms of FSS. In the assessment of quality of life, only the physical function domain was significantly poorer in Group 1 than in Group 2 (p < 0.05). Physical function was correlated with subjective sleep quality, sleep disorder, and daytime dysfunction; fatigue was correlated with sleep disorder, daytime dysfunction, and use of sleep medications (p < 0.05). There was a correlation between the total PSQI score and physical functioning and fatigue (p < 0.05).Conclusion: Female patients with lipedema have poor sleep quality and decreased quality of life. Sleep disturbance is associated with both physical function and fatigue. Quality of sleep should be questioned in every assessment of patients with lipedema.

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.

Lipedema is a chronic condition characterised by abnormal fat distribution in the limbs, particularly the lower body. It leads to accumulation of tender,

For the millions of women living with lipedema worldwide, finding effective treatment options has been a long and frustrating journey. However, recent research is shedding light on a potential new avenue for treatment: GLP-1 receptor agonists, particularly tirzepatide. What is Lipedema? Lipedema is a chronic medical condition characterized by the abnormal accumulation of fat cells,

Liposuction in lipedema is a safe and effective treatment, but there currently are no studies analyzing the individual complications of water-jet-assisted liposuction in lipedema or the impact of the cannula’s design.To answer the question which WAL cannula is the safest in lipedema patients, and providing practitioners with the data they need to make an informed decision about the cannula they choose.We retrospectively analyzed complications and their underlying risk factors in 117 patients across 243 cases. Groups were formed by diameter (Ø) and number of ports of the used cannulas. Unpaired t-Tests, Fisher’s exact tests and chi-squared tests were used to analyze the patients’ characteristics for the complication rates across the cannulas.Cannulas with 8 ports showed statistically significantly higher hemoglobin loss (p = 0.011), shorter incision-to-suture time (p = 0.023), and higher volume of aspirated fat (p &lt; 0.001). The same results occurred when comparing the Ø 3.8mm cannulas that differ in the number of ports (4 versus 8 ports). The Ø 4.8mm group showed a significantly increased rate of wound healing disorders compared to the Ø 3.8mm group (p = 0.041) and a statistically significantly higher aspirated fat volume (p = 0.014).No specific cannula showed superior safety in terms of complication rates. However, 8 port cannulas facilitated a faster aspiration of large volumes and reduced the incision-to-suture time compared to 4 port cannulas. This benefit was accompanied by a grater loss of hemoglobin. In contrast, cannula diameter played a less significant role in aspiration speed and did not increase the hemoglobin loss.

Background: Lipedema, a chronic condition affecting mostly women, involves painful bilateral increase of subcutaneous adipose tissue. The societal impact of this disease is still poorly understood. This study aimed to validate the Lymphedema Quality-of-Life Questionnaire (LYMQOL) for lipedema patients in Germany, assessing its feasibility, reliability, and validity.Methods and Results: A total of 81 German-speaking stage II lipedema patients were asked to complete both the LYMQOL (arm and leg versions) and the Short Form Health Survey (SF-36) questionnaires twice, and this was 2 weeks apart. Feasibility was evaluated through response rates, scale structure via factor analysis, validity through SF-36 correlations, and reliability through internal consistency and test-retest reliability analysis. A valid 68% response rate was achieved. Both arm and leg versions demonstrated construct validity with significant correlations to SF-36 subscales. Internal consistency for the leg version was acceptable to excellent, and good to excellent for the arm version. Test-retest reliability was very good for both versions.Conclusions: This study validates the LYMQOL as a robust tool for assessing lipedema patients’ quality of life, and also validates the German translation contained in this article. We hope to fill a critical research gap and support future clinical studies aiming at enhancing patient care.

Background/Objectives: Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation and inflammation, predominantly affecting women. While recent evidence suggests a systemic pro-inflammatory state in lipedema, the role of diet in modulating inflammation remains underexplored. This study assessed the anti-inflammatory potential of a Mediterranean-style ketogenic diet and its effects after 7 months of adherence on systemic inflammation markers (CRP and IL-6) in women with lipedema (n = 24) and a control group with overweight/obesity (n = 24). Methods: The Dietary Inflammatory Index (DII) was used to characterize the inflammatory potential of the diet throughout the intervention. Dietary intake was analyzed pre- and post-intervention, and anthropometric, body composition, and biochemical parameters were measured. Results: Beyond its beneficial effects on body composition (significant reductions in body weight, fat, leg circumferences, and visceral fat), the intervention diet also demonstrated anti-inflammatory potential. In lipedema, baseline diet showed a pro-inflammatory DII profile (DII/day = 3.04), which was reduced by about 1.5 points after the intervention (p = 0.008). When expressed per 1000 kcal, the DII values were markedly lower for both baseline (DII = 0.22) and intervention diet (DII = ~0.01). Following the intervention diet, reduction in CRP (-0.39, p = 0.016) and IL-6 levels (-0.33, p = 0.034) in lipedema were observed. A significant positive association was observed between the intervention diet's DII and CRP (r = 0.55, p = 0.005), and between the baseline diet's DII and IL-6 (r = 0.50, p = 0.013) in lipedema group. Conclusions: These findings suggest that ketogenic diet rich in anti-inflammatory and antioxidant nutrients can reduce systemic inflammation in lipedema patients, independently of caloric restriction.

BACKGROUND: Lipedema is a chronic disorder of adipose tissue that predominantly affects women and is frequently misdiagnosed as obesity or lymphedema. Traditionally associated with the lower extremities, lipedema can also involve the abdominal region, although there are currently no established diagnostic criteria for abdominal lipedema. This study aims to propose a diagnostic algorithm for abdominal lipedema based on clinical features, macroscopic observations, and ultrasound findings. METHODS: This retrospective study analyzed data from 327 patients treated between March 2018 and March 2024 for lipedema, including those with abdominal involvement. Clinical evaluations, ultrasound imaging, and surgical outcomes were examined to assess the prevalence and characteristics of abdominal lipedema. Patients were classified based on lipedema severity, and criteria for abdominal lipedema diagnosis were established through clinical and imaging data. RESULTS: The study identified that abdominal involvement increases with the severity of lipedema, with 31% of patients with stage II lipedema and 70% of those with stage III lipedema exhibiting abdominal manifestations. The proposed diagnostic algorithm includes maximum, major, and minor criteria, such as symmetrical fat deposition, pain, and non-responsiveness to diet and exercise. Specific threshold values for each category were defined to establish the diagnosis. The findings highlight the existence of both ascending (from legs to abdomen) and descending (from arms to abdomen) centripetal progression patterns, challenging traditional notions that limit lipedema to the extremities CONCLUSION: Abdominal lipedema is a significant and underrecognized manifestation of the condition, requiring specific diagnostic criteria to ensure accurate diagnosis and appropriate treatment. The study proposes a diagnostic framework based on clinical and imaging features that can improve the recognition and management of abdominal lipedema. Multidisciplinary treatment approaches, including both conservative measures and surgical interventions such as abdominoplasty and liposuction, are recommended to improve patient outcomes. 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 .