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BACKGROUND: Lipoedema is a painful adipose tissue disorder, affecting the limbs of women, that is resistant to diet and exercise. The purpose of the study was to evaluate the retrospective health-related quality-of-life (HRQoL) outcomes for patients with lower limb lipoedema (LLL) following tumescent liposuction (TL). METHODS: Forty-seven patients received TL over 5 years from 2015-2020 for LLL. As part of their routine treatment evaluation, each patient completed 4 validated HRQoL questionnaires at initial assessment. The questionnaires examined the patients' experiences relating to anxiety and depression, lower extremity function, appearance, and symptoms. The same questionnaires were posted to the patients after an average of 12 months post-procedure/s to establish the outcomes of the intervention. RESULTS: The study demonstrated that patients' HRQoL improved at 12 months (average) following TL. The results of all the questionnaires were statistically significant, and patients with stage 3 LLL showed the most improvement in outcomes. CONCLUSION: The findings demonstrated that TL achieves positive HRQoL outcomes in patients with LLL; however, long-term follow-up is needed to determine if the benefits sustain. Additionally, larger prospective controlled studies are required to provide robust evidence for this procedure.

Body composition (BC) measured by DXA differs between devices. We aimed to compare regional and total BC measurements assessed by the Hologic Horizon A and the GE Lunar iDXA devices; to determine device-specific calibration equations for each BC parameter; and to assess the impact of this standardization procedure on the assessment of sarcopenia, lipedema, obesity, and cardiovascular risk with DXA. A total of 926 postmenopausal women (aged 72.9 ± 6.9 yr, height 160.3 ± 6.6 cm, weight 66.1 ± 12.7 kg) underwent BC assessment on each device within 1 h, following the ISCD guidelines. The included sample was split into 80% train and 20% test datasets stratified by age, height, and weight. Inter-device differences in BC parameters were assessed with Bland-Altman analysis, Pearson or Spearman correlation coefficients, and t-tests or Wilcoxon tests. The equations were developed in the train dataset using backward stepwise multiple linear regressions and were evaluated in the test dataset with the R-squared and mean absolute error. We compared the abovementioned BC-derived health conditions before and after standardization in the test set with respect to relative risk, accuracy, Kappa score, and McNemar tests. Total and regional body masses were similar (p>.05) between devices. BMC was greater for all regions in the Lunar device (p<.05), while fat and lean masses differed among regions. Regression equations showed high performance metrics in both datasets. The BC assessment from Hologic classified 2.13 times more sarcopenic cases (McNemar: p<.001), 1.39 times more lipedema (p<.001), 0.40 times less high cardiovascular risk (p<.001), and similarly classified obesity (p>.05), compared to Lunar. After standardization, the differences disappeared (p>.05), and the classification metrics improved. This study discusses how hardware and software differences impact BC assessments. The provided standardization equations address these issues and improve the agreement between devices. Future studies and disease definitions should consider these differences.

This S2k guideline was developed on the initiative and under the German Society of Phlebology and Lymphology (DGPL) leadership. The guideline aims to optimize the diagnosis and treatment of lipedema. It is intended to bring together the different approaches of the respective professional groups in a consensus-based manner and thus offer a basic concept for the best possible treatment of patients with lipedema. Sixty recommendations were formulated and agreed on in diagnostics, conservative and surgical treatment options, psychosocial factors and self-management. The guideline is intended to reflect the current scientific knowledge and be widely used for diagnosis and treatment recommendations for patients with lipedema. In particular, the guideline comments on diagnostic criteria, differential diagnoses, and coinciding clinical pictures, their influence on diagnosis and treatment, sensible treatment measures, and self-management options. The lipedema guideline summarizes the current national and international evidence and the German expert consensus and derives recommendations for the best treatment for patients with lipedema. The recommendations in the guideline are intended as an orientation aid in the sense of action and decision-making corridors from which deviations are possible in justified cases.

Introduction Lipedema is a relatively common, frequently misdiagnosed, chronic condition often treated by liposuction when conservative therapies fail. Techniques such as traditional tumescent liposuction (TTL), power-assisted liposuction (PAL), and water-jet-assisted liposuction (WAL), are popular surgical interventions, although it is unclear how these techniques compare. This meta-analysis aims to assess the efficacy and safety of liposuction in patients with lipedema. Methods Relevant English lipedema studies published in PubMed from January 2003 to April 2023 were identified. Ten articles with postoperative outcomes and complications data were included (2 TTL, 5 PAL, 1 WAL, 2 articles used both PAL and WAL). Results were summarized using descriptive statistics, and a randomized effects model was used to evaluate heterogeneity. Results A total of 2,542 procedures in 906 patients were included. Combined outcomes for all techniques significantly improved pain, bruising, edema, tension, pressure sensitivity, cosmetic impairment, and general impairment (all P < 0.00001). Results for TTL, PAL, and WAL led to significant improvements in pain reduction (P = 0.0005), bruising, swelling, pressure sensitivity, or cosmetic impairment (all P < 0.05). WAL more effectively reduced tension and general impairment (all P < 0.005), but heterogeneity for these outcomes was high. Overall complication rates were low for studies that utilized TTL (1.5%), PAL (4.0%), WAL (0%), and both PAL and WAL (2.3%). Conclusion Liposuction techniques, including TTL, PAL, and WAL, result in significant symptom improvement in lipedema patients with a relatively low complication rate. WAL may potentially result in a more substantial reduction of tension and general impairment with fewer complications; however, only a single study performed this method of liposuction exclusively. This is the first meta-analysis investigating liposuction data in lipedema treatment.

We evaluated the effect of compression leggings with micromassage in association with physical activity on women with lipedema, not previously treated and without recent changes in body weight. The treatment resulted in an improvement in all subjective parameters, in spontaneous and evoked pain, in the volume of the limbs, in the absence of significant changes in body weight, and regardless of the duration of use, age, years of illness, the clinical stage, and body mass index (BMI). Evoked pain did not improve in areas affected by untreated lipedema; foot circumferences did not increase. We found a significant reduction in the thickness of subcutaneous adipose tissue (SAT) and skin evaluated in multiple points of the lower limb. Micromassage compression leggings are proposed as an integral part of conservative treatment. A method is proposed for the clinical evaluation of evoked pain, called the Progressive Pain Check (PPC), which allows for the calculation of a numerical score called the Ricolfi-Patton Score (RPS) and for the ultrasound evaluation of tissues. The method is simple and repeatable and allows for completion of the clinical evaluation of the patient at diagnosis and for an evaluation of the effects of various treatments, even applied to just one side of the body.

PURPOSE OF REVIEW: This consensus statement from the Italian Society of Motor and Sports Sciences (Società Italiana di Scienze Motorie e Sportive, SISMeS) and the Italian Society of Phlebology (Società Italiana di Flebologia, SIF) provides the official view on the role of exercise as a non-pharmacological approach in lipedema. In detail, this consensus statement SISMeS - SIF aims to provide a comprehensive overview of lipedema, focusing, in particular, on the role played by physical exercise (PE) in the management of its clinical features. RECENT FINDINGS: Lipedema is a chronic disease characterized by abnormal fat accumulation. It is often misdiagnosed as obesity, despite presenting distinct pathological mechanisms. Indeed, recent evidence has reported differences in adipose tissue histology, metabolomic profiles, and gene polymorphisms associated with this condition, adding new pieces to the complex puzzle of lipedema pathophysiology. Although by definition lipedema is a condition resistant to diet and PE, the latter emerges for its key role in the management of lipedema, contributing to multiple benefits, including improvements in mitochondrial function, lymphatic drainage, and reduction of inflammation. Various types of exercise, such as aquatic exercises and strength training, have been shown to alleviate symptoms and improve the quality of life of patients with lipedema. However, standardized guidelines for PE prescription and long-term management of patients with lipedema are lacking, highlighting the need for recommendations and further research in this area in order to optimise therapeutic strategies.

Lymphological and fatty tissue disorders of the legs are increasingly tying up capacities in the health care system. This is related to the increase in obesity disease to almost endemic proportions in our society. Although the term lipedema was coined in the 1950s, it has only now become really well known. Women with lipedema suffer from symmetrical and disproportional fat deposition on both legs, accompanied by tenderness or strong pain especially on touch. Over 50 years, this condition has been underdiagnosed. Women with lipohypertrophy (same fat disproportion without pain) fear they suffer from lipedema and are misguided by false information, claiming treatment, as well as liposuction reimbursed by health care systems. Affected women suffer greatly from misinformation but also from overdiagnosis. The aim of this work is to make differential diagnosis easier for the health practitioner. On the basis of descriptions on visual inspection and palpation of the affected legs, the differential diagnosis is explained here, supported with many pictures. As a result, differentiation of the entities lipedema, lipohypertrophy, obesity, and lymphedema and their mixed forms is made easier for health practitioners in their daily work. Many studies are still needed to better understand the entity lipedema, and efforts are underway to change the name to avoid misunderstandings, as the condition “lipedema” does not seem to have water in the fatty tissue.

Lymphedema and lipedema are chronic debilitating disorders that most commonly affect the upper and lower extremities. Although they can appear similar, they differ in important ways, which the authors of this article review and contrast.

BACKGROUND: Lipedema is the progressive symmetrical deposition of subcutaneous fat and fluid in the lower body, ordinarily sparing the trunk, upper limbs, face, and neck. It may follow an autosomal dominant inheritance pattern. The gold standard treatment for lipedema is complete decongestive therapy, consisting of manual lymphatic drainage and compression garments. This scoping review assessed the existing literature on the effectiveness of liposuction as an alternative treatment for lipedema. METHODS: A scoping review of electronically available literature within PubMed, Scopus, and Cochrane focused on liposuction as a treatment for lipedema considering the following inclusion criteria: human studies, case series of 10 or more, controlled trials, randomized controlled trials, patient-reported outcome measurement studies, survey analyses, descriptive studies, retrospective analyses, recurrence included, follow-up of 6 months or more, age 18 years or older, and treatment modality being liposuction. RESULTS: Thirteen studies were selected. Nine studies reported decreased compression therapy use among patients following liposuction. No studies reported a long-term increase in compression therapy following liposuction. Studies found self-reported improvements in pain, mobility, bruising, and overall quality of life for patients following liposuction, many of whom had previously been on compressive therapy. Studies reported low rates of serious adverse events following liposuction, including deep vein thrombosis, pulmonary embolism, and infection. CONCLUSIONS: These results suggest that liposuction can be a viable treatment alternative to compression therapy for lipedema in patients whose compression therapy has not been helpful. However, there is not enough evidence to say whether liposuction is as effective as compression for patients first presenting with lipedema.

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue samples were collected from affected areas of both lipedema and healthy participants. For single-cell RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed three distinct adipocyte populations at play in lipedema. These populations have unique gene signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte, and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures and functional roles. The interplay between these adipocyte subtypes offers promising insights into the complex pathophysiology of lipedema.

<p id="p1">Despite extensive research during the last couple of years, lipedema still appears enigmatic in respect to its pathogenesis. In our in vitro study, we have set out to further characterize lipedema adipocytes, concentrating on gene and protein expression, which might help to develop ideas explaining the excessive accumulation of adipose tissue in women with lipedema. Using 2D cultures we show that gene expression in lipedema and non-lipedema adipocytes differs significantly in terms of genes related to lipid droplet size determination, insulin signaling and glucose uptake. A pronounced hypertrophy, recognizable by a significantly increased average lipid droplet size, was visible in differentiated lipedema adipocytes grown in 3D cultures. In addition, gene and protein expression related to inflammation and fibrosis were upregulated in lipedema adipocytes compared to controls, supporting earlier reports. Taken together, results from our in vitro studies suggest that lipedema adipose cells are capable of retaining their hypertrophic nature under culture conditions and open new aspects focusing on insulin signaling and PDGFRA-mediated balancing of adipogenic versus fibrogenic differentiation of lipedema adipose tissue.</p>

Lipedema and lymphedema are physically similar yet distinct diseases that are commonly misdiagnosed. We previously reported that lipedema and lymphedema are associated with increased risk for venous thromboembolism (VTE). The underlying etiology of the prothrombotic profile observed in lipedema and lymphedema is unclear, but may be related to alterations in platelets. Our objective was to analyze the platelet transcriptome to identify biological pathways that may provide insight into platelet activation and thrombosis. The platelet transcriptome was evaluated in patients with lymphedema and lipedema, then compared to control subjects with obesity. Patients with lipedema were found to have a divergent transcriptome from patients with lymphedema. The platelet transcriptome and impacted biological pathways in lipedema were surprisingly similar to weight-matched comparators, yet different when compared to overweight individuals with a lower body mass index (BMI). Differences in the platelet transcriptome for patients with lipedema and lymphedema were found in biological pathways required for protein synthesis and degradation, as well as metabolism. Key differences in the platelet transcriptome for patients with lipedema compared to BMI-matched subjects involved metabolism and glycosaminoglycan processing. These inherent differences in the platelet transcriptome warrant further investigation, and may contribute to the increased risk of thrombosis in patients with lipedema and lymphedema.

Abstract Background Lipedema is a chronic, incurable disorder characterized by painful fat accumulation in the extremities. While the application of liposuction in lipedema management has become increasingly popular, the safety and effectiveness of this approach remain contentious. Our systematic review and meta-analysis aimed to assess various liposuction modalities in lipedema management to verify their safety and efficacy. Methods In-line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a comprehensive literature review from inception until March 2023 using the following electronic databases: CENTRAL, MEDLINE, Google Scholar, and EMBASE. Results From the 562 initially identified articles, 20 met our inclusion/exclusion criteria for evaluation. Our review encompassed 14 prospective cohort studies, 3 retrospective studies, 2 case series, and 1 cross-sectional study. A meta-analysis of nine articles revealed a notable improvement in the quality of life, pain, pressure sensitivity, bruising, cosmetic impairment, heaviness, walking difficulty, and itching among lipedema patients who underwent liposuction. Although complications such as inflammation, thrombosis, seroma, hematoma, and lymphedema-related skin changes were reported, severe complications were rare. Crucially, no instances of shock, recurrence, or mortality were reported. Conclusion Liposuction is a safe and beneficial therapeutic intervention for managing lipedema symptoms and enhancing quality of life. However, the impact of liposuction on secondary lymphedema remains unreported in the literature. Further high-quality, large-scale trials are necessary to assess the safety and effectiveness of different liposuction modalities. These studies will contribute valuable insights to optimize liposuction as a therapeutic option for individuals with lipedema. Level of Evidence I, risk/prognostic study.

The role of artificial intelligence (AI) in healthcare is evolving, offering promising avenues for enhancing clinical decision making and patient management. Limited knowledge about lipedema often leads to patients being frequently misdiagnosed with conditions like lymphedema or obesity rather than correctly identifying lipedema. Furthermore, patients with lipedema often present with intricate and extensive medical histories, resulting in significant time consumption during consultations. AI could, therefore, improve the management of these patients. This research investigates the utilization of OpenAI's Generative Pre-Trained Transformer 4 (GPT-4), a sophisticated large language model (LLM), as an assistant in consultations for lipedema patients. Six simulated scenarios were designed to mirror typical patient consultations commonly encountered in a lipedema clinic. GPT-4 was tasked with conducting patient interviews to gather medical histories, presenting its findings, making preliminary diagnoses, and recommending further diagnostic and therapeutic actions. Advanced prompt engineering techniques were employed to refine the efficacy, relevance, and accuracy of GPT-4's responses. A panel of experts in lipedema treatment, using a Likert Scale, evaluated GPT-4's responses across six key criteria. Scoring ranged from 1 (lowest) to 5 (highest), with GPT-4 achieving an average score of 4.24, indicating good reliability and applicability in a clinical setting. This study is one of the initial forays into applying large language models like GPT-4 in specific clinical scenarios, such as lipedema consultations. It demonstrates the potential of AI in supporting clinical practices and emphasizes the continuing importance of human expertise in the medical field, despite ongoing technological advancements.

Background: Lipedema is a subcutaneous adipose tissue disorder characterized by increased pathological adipocytes mainly in the extremities. Vitamin D is stored in adipocytes, and serum levels inversely correlate with BMI. As adipocytes are removed during liposuction, lipedema patients might be prone to further substantial vitamin D loss while their levels are already decreased. Therefore, we examined the effect of liposuction on perioperative serum 25-hydroxyvitamin D levels. Methods: In patients undergoing lipedema liposuction, blood samples were obtained pre- and postoperatively. Statistical analyses were performed to correlate the volume of lipoaspirate, patients' BMI and number of sessions to vitamin D levels. Results: Overall, 213 patients were analyzed. Mean liposuction volume was 6615.33 ± 3884.25 mL, mean BMI was 32.18 ± 7.26 kg/m2. mean preoperative vitamin D levels were 30.1 ± 14.45 ng/mL (borderline deficient according to the endocrine society) and mean postoperative vitamin D levels were 21.91 ± 9.18 ng/mL (deficient). A significant decrease in serum vitamin D was seen in our patients (p < 0.001) of mean 7.83 ng/mL. The amount of vitamin D loss was not associated with BMI or aspiration volume in our patients (p > 0.05). Interestingly, vitamin D dynamics showed a steady drop regardless of volume aspirated or preoperative levels. Conclusions: Many lipedema patients have low vitamin D levels preoperatively. Liposuction significantly reduced these levels additionally, regardless of aspirated volume or BMI. However, vitamin D loss was constant and predictable; thus, patients at risk are easily identified. Overall, lipedema patients undergoing liposuction are prone to vitamin D deficiency, and the long-term effects in this population are currently unknown.

Lipedema is a chronic, idiopathic, and painful disease characterized by an excess of adipose tissue in the extremities. The goal of this study is to characterize the gene expression of estrogen receptors (ERα and ERβ), G protein-coupled estrogen receptor (GPER), and ER-metabolizing enzymes: hydroxysteroid 17-beta dehydrogenase (HSD17B1, 7, B12), cytochrome P450 (CYP19A1), hormone-sensitive lipase (LIPE), enzyme steroid sulfatase (STS), and estrogen sulfotransferase (SULT1E1), which are markers in Body Mass Index (BMI) and age-matched non-lipedema (healthy) and lipedema ASCs and spheroids. Flow cytometry and cellular proliferation assays, RT-PCR, and Western Blot techniques were used to determine the expression of ERs and estrogen-metabolizing enzymes. In 2D monolayer culture, estrogen increased the proliferation and the expression of the mesenchymal marker, CD73, in hormone-depleted (HD) healthy ASCs compared to lipedema ASCs. The expression of ERβ was significantly increased in HD lipedema ASCs and spheroids compared to corresponding healthy cells. In contrast, ERα and GPER gene expression was significantly decreased in estrogen-treated lipedema spheroids. CYP19A1 and LIPE gene expressions were significantly increased in estrogen-treated healthy ASCs and spheroids, respectively, while estrogen upregulated the expression of PPAR-ϒ2 and ERα in estrogen-treated lipedema-differentiated adipocytes and spheroids. These results indicate that estrogen may play a role in adipose tissue dysregulation in lipedema.

Lipedema is a poorly understood disorder of adipose tissue characterized by abnormal but symmetrical deposition of subcutaneous white adipose tissue (WAT) in proximal extremities. Here, we propose that the underlying cause for lipedema could be triggered by a selective accumulation of bacterial lipopolysaccharides (LPS; also known as endotoxin) in gluteofemoral WAT. Together with a malfunctioning complement system, this induces low-grade inflammation in the depot and raises its uncontrollable expansion. Correspondingly, more attention should be paid in future research to the endotoxemia prevalent in patients with lipedema. We would like to propose that proper management of endotoxemia can reduce the progression and even improve the state of disease in patients with lipedema.

This study aimed to develop a novel predictive equation for calculating resting metabolic rate (RMR) in women with lipedema. We recruited 119 women diagnosed with lipedema from the Angiology Outpatient Clinic at Wroclaw Medical University, Poland. RMR was assessed using indirect calorimetry, while body composition and anthropometric measurements were conducted using standardized protocols. Due to multicollinearity among predictors, classical multiple regression was deemed inadequate for developing the new equation. Therefore, we employed machine learning techniques, utilizing principal component analysis (PCA) for dimensionality reduction and predictor selection. Regression models, including support vector regression (SVR), random forest regression (RFR), and k-nearest neighbor (kNN) were evaluated in Python's scikit-learn framework, with hyperparameter tuning via GridSearchCV. Model performance was assessed through mean absolute percentage error (MAPE) and cross-validation, complemented by Bland-Altman plots for method comparison. A novel equation incorporating body composition parameters was developed, addressing a gap in accurate RMR prediction methods. By incorporating measurements of body circumference and body composition parameters alongside traditional predictors, the model's accuracy was improved. The segmented regression model outperformed others, achieving an MAPE of 10.78%. The proposed predictive equation for RMR offers a practical tool for personalized treatment planning in patients with lipedema.

OBJECTIVE: The primary objective of this study was to evaluate the effect of a low-carbohydrate diet (LCD) compared with a control diet on pain in female patients with lipedema. The secondary objectives were to compare the impact of the two diets on quality of life (QoL) and investigate potential associations of changes in pain with changes in body weight, body composition, and ketosis. METHODS: Adult female patients with lipedema and obesity were randomized to either the LCD or control diet (energy prescription: 1200 kcal/day) for 8 weeks. Body weight and body composition, pain (Brief Pain Inventory measured pain), and QoL (RAND 36-Item Health Survey [RAND-36], Impact of Weight on Quality of Life [IWQOL]-Lite, and Lymphoedema Quality of Life [LYMQOL]) were measured at baseline and at postintervention. RESULTS: A total of 70 female patients (age, mean [SD], 47 [11] years; BMI 37 [5] kg/m2) were included. The LCD group had greater weight loss (-2.8 kg; 95% CI: -4.1 to -1.0; p < 0.001) and larger reduction in pain now (-1.1; 95% CI: -1.9 to -0.3; p = 0.009) compared with the control group. No association was found between changes in pain now and weight loss. Both groups experienced improvements in several QoL dimensions. CONCLUSIONS: Diet-induced weight loss in women with lipedema can improve QoL. An energy-restricted LCD seems to be superior to a standard control diet in reducing pain.