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Lipedema is a chronic disease in females characterized by pathologic subcutaneous adipose tissue expansion and hitherto remains without druggable targets. In this observational study, we investigated the molecular hallmarks of lipedema using an unbiased multi-omics approach. We found adipokine dysregulation in lipedema patients participating in a cross-sectional clinical study (ClinicalTrial.gov, NCT02838277), pointing towards the adipocyte as a key player. Analyses of newly generated transcriptomic (SRA, PRJNA940039) and proteomic (ProteomeXchange, PXD058489) datasets of early- and late-stage lipedema samples revealed a local downregulation of factors involved in inflammation. Concomitantly, factors involved in cellular respiration, oxidative phosphorylation, as well as in mitochondrial organization were upregulated. Measuring a cytokine and chemokine panel in the serum of non-menopausal women, we observed little systemic changes in inflammatory markers, but a trend towards increased VEGF. Metabolomic and lipidomic analyses highlighted altered circulating glutamic acid, glutathione, and sphingolipid levels, suggesting a broader dysregulation of metabolic and inflammatory processes. We subsequently benchmarked a set of models to accurately predict lipedema using serum factor measurements (sLPM). Our study of the molecular signature of lipedema thus provides not only potential targets for therapeutic intervention, but also candidate markers of disease development and progression.

Our data support the idea that cell alterations happen in the early stages of adipocyte development (endothelium/pericyte) in the adipose organ of women affected by lipedema.

Lipedema diagnosis is heavily reliant on patient history. Various objective assessments have been suggested; however, a standardized measurement process is lacking. A systematic review was undertaken to identify which imaging and measurement tools are used in lipedema quantification and to review their protocols. Six databases were searched with two reviewers screening citations for inclusion. Full peer-reviewed publications that included defined lipedema diagnosis criteria, no male cases within comparative cohorts, and used an imaging or measurement tool to quantify lipedema were included. Twenty studies met the inclusion criteria using 13 different tools to quantify individual physical lipedema characteristics to either enable differential diagnosis, and/or quantify treatment effect: tape measure, perometry, durometry, tonometry, bioimpedance spectroscopy, tissue di-electric constant, ultrasound, Dual-Energy X-ray Absorptiometry, magnetic resonance imaging (MRI), noncontrast MRI lymphangiography, Indocyanine green lymphography, lymphoscintigraphy, and dynamic lymphangiography. Eight imaging and five measurement tools assessed lymphatic transport disturbances (n = 8), limb size/volume (n = 4), adipose tissue thickness/mass/volume (n = 3), and tissue fluid presence (n = 2). Multiple tools were only used in studies completed in 2020 or later. A lack of consistency exists in tool protocols, measurement locations, and outcome analysis. Limited reporting of clinimetrics with data derived from small cohorts and heterogenous populations impacted the ability to recommend tools for clinical practice and research. Various tools were used for objective lipedema assessment; however, consistency in approach was lacking. Further investigations are required to establish the validity and reliability of measurement and imaging tools, protocols, measurement points, and outcome reporting/interpretation to quantify the physical attributes of lipedema.

This study underscores the need for tailored self-management interventions for people with lipoedema. The adaptation of existing self-management strategies from other chronic conditions should take into account the specific needs, barriers, and facilitators of people with lipoedema and their HCPs.

Background/Objectives: Lipedema is a progressive disease that results in the bilateral and symmetrical accumulation of subcutaneous fat in the legs and/or arms, affecting almost exclusively women. Methods: A comprehensive review of the peer-reviewed literature was conducted between November 2024 and February 2025. Results: The pathophysiology of lipedema is complex and, especially in the early stages, shows similarities to obesity, involving adipocytes, adipose tissue-resident macrophages, and endothelial cells. In lipedema, systemic levels and the adipocyte expression of the classical adipokines adiponectin and leptin appear normal, while it remains unclear if markers of inflammation and oxidative stress are increased. Macrophages in the adipose tissue of patients have an anti-inflammatory M2 phenotype and express high levels of the scavenger receptor CD163. These cells affect adipogenesis and seem to have a central role in adipose tissue accumulation. Increased lymphatic and blood vessel permeability are comorbidities of lipedema that occur in early disease states and may contribute to disease progression. Conclusions: This review summarizes our current understanding of the pathophysiology of lipedema with a focus on the role of stromal vascular localized M2 macrophages.

Background Lipedema is considered an inflammation-related disease, and low-carbohydrate ketogenic diets may help reduce inflammation. However, no randomized controlled trials have investigated the effect of a low-carbohydrate ketogenic diet on inflammatory markers in females with lipedema. Objectives To compare changes in inflammatory and fibrosis-associated markers after a low-energy low-carbohydrate diet (LCD) compared with a low-fat diet in females with lipedema, and to explore potential associations between changes in pain and changes in inflammatory and fibrosis-associated markers. Methods Females with lipedema and obesity were randomly assigned to either an LCD or low-fat diet (both 1200 kcal/d) for 8 weeks. Body composition [fat mass (FM) and fat-free mass] and the plasma concentrations of high-sensitivity C-reactive protein (hsCRP), cytokines, and fibrosis-associated markers were measured pre- and postintervention. Results A total of 70 females were included (35/group) (mean age: 47.3 ± 10.9 y, BMI: 36.9 ± 4.9 kg/m2). Both groups lost weight and FM (kg and %), with a greater reduction in the LCD group. A reduction in macrophage inflammatory protein-1ß, tumor necrosis factor-α, and hsCRP was seen in the LCD group only, despite no significant differences between groups. No associations were found between changes in pain and changes in cytokines and fibrosis-associated markers. Conclusions Changes in cytokines and fibrosis-associated markers did not differ between low-energy LCD and low-fat diets in females with lipedema, despite a beneficial profile in the LCD group. Inflammation does not seem to be involved in pain reduction following LCD in this patient group. Trial registration number This trial was registered at clinicaltrials.gov as NCT04632810.

OBJECTIVES: To evaluate the presence of lipedema and lipedema-related factors in fibromyalgia patients. METHODS: The study included 100 female patients over the age of 18 who met the fibromyalgia diagnostic criteria. The patients were evaluated for the presence/stages of lipedema. The body mass index (BMI), waist-hip ratio, waist-height ratio, and presence of hematoma tendency/telangiectasias were recorded. Patients were asked to mark the severity of their pain (widespread/on lipedema) on a 10 cm visual analog scale (VAS). The ACR 2016 Fibromyalgia Diagnostic Criteria, The Beck Depression Inventory (BDI), and The Revised Fibromyalgia Impact Questionnaire were applied. RESULTS: Lipedema was observed in 50% of the patients (58% Stage 1 lipedema). In the lipedema group, age, duration of fibromyalgia diagnosis, hematoma tendency/presence of telangiectasias (for all; p < .001), menopausal status (p = .004), BDI score (p = .04), BMI (p = .02), history of medication for fibromyalgia (p = .01) were higher, and age at menarche (p = .01) was lower. Lipedema stage was moderately positively correlated with BMI, number of pregnancies (for both; r:0.53 p < .001) and waist-height ratio (r:0.43 p:0.002), while VAS-lipedema pain intensity was strongly positively correlated with VAS-widespread pain intensity (r:0.62 p < .001), and moderately positively correlated with symptom severity score (r:0.55 p < .001), BMI (r:0.54 p < .001), and fibromyalgia severity score (r:0.51 p < .001). Long fibromyalgia diagnosis time (p: 0.005), and low age at menarche (p: 0.05) were significant risk factors for the presence of lipedema. CONCLUSIONS: Lipedema is common in fibromyalgia patients. Long fibromyalgia diagnosis time and low age at menarche are significant risk factors for the presence of lipedema.

Background: One of the main challenges in managing lymphedema and lipedema is the lack of valid and reliable objective measures for diagnosis and follow-up. This study was aimed at gathering evidence regarding the objective measures of cardiorespiratory fitness (CRF) among these populations., Methods: Scopus, PubMed, and Embase were searched for observational studies investigating the objective measures of CRF among individuals with lipedema and lymphedema. Both primary and secondary lymphedema were included. Different CRF measures reported by the included articles were determined, and the main outcomes regarding these measurements were extracted. The meta-analysis was performed to compare the pooled mean 6-min walk test (6MWT) between individuals with lower limb lymphedema and lipedema using STATA software (Version 17.0)., Results: Eight articles were included, and the majority of participants were female. Four distinct objective measures of CRF were reported among the included articles, including hemodynamic indices, spirometry indices, VO2 peak, and 6MWT. The mean VO2 peak was significantly lower among women with breast cancer–related lymphedema; however, there was no correlation between affected limb volumes and the VO2 peak. The meta-analysis revealed a lower mean 6MWT among individuals with lipedema compared to lymphedema (pooled difference: 37.71 [confidence interval (CI): 5.19–70.22], p value: 0.02, I2: 0%). Also, there was a significant relationship between 6MWT and subjective measures of CRF, such as the Short Form 36 (SF-36) physical function score, in one included article., Conclusion: While limited evidence exists on the objective measures of CRF among individuals with lymphedema and lipedema, there might be a significant difference in 6MWT between these two groups.

<span><b><i>Purpose:</i></b> The study's main objective was to assess the efficacy and safety of TANIT, a platform combining functional dermal stimulation with damped bioactive current and mechanical stimulation to reduce adipose tissue (AT) in patients with stage I (SI) or II (SII) lipedema. <b><i>Method</i></b></span> …

Lipedema is characterized by abnormal fat deposition in areas such as the arms, hips, buttocks, and thighs, sparing the hands and feet. Symptoms include pain, bruising, edema, and subcutaneous nodules, which resist traditional interventions such as diet and exercise. Despite increasing recognition, …

Lipedema was seen to be stable in two-thirds of the patients. Age was not related to progression. Progression was related to WHtR increase, which is an indicator of abdominal fat gain. This demonstrates the relationship between fat gain and lipedema progression.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly being used to treat diabetes and obesity. However, their effectiveness and risks have not yet been systematically evaluated in a comprehensive set of possible health outcomes. Here, we used the US Department of Veterans Affairs databases to build a cohort of people with diabetes who initiated GLP-1RA (n = 215,970) and compared them to those who initiated sulfonylureas (n = 159,465), dipeptidyl peptidase 4 (DPP4) inhibitors (n = 117,989) or sodium−glucose cotransporter-2 (SGLT2) inhibitors (n = 258,614), a control group composed of an equal proportion of individuals initiating sulfonylureas, DPP4 inhibitors and SGLT2 inhibitors (n = 536,068), and a control group of 1,203,097 individuals who continued use of non-GLP-1RA antihyperglycemics (usual care). We used a discovery approach to systematically map an atlas of the associations of GLP-1RA use versus each comparator with 175 health outcomes. Compared to usual care, GLP-1RA use was associated with a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer’s disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions. There was an increased risk of gastrointestinal disorders, hypotension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis and drug-induced pancreatitis associated with GLP-1RA use compared to usual care. The results provide insights into the benefits and risks of GLP-1RAs and may be useful for informing clinical care and guiding research agendas.

Background: Despite its estimated high prevalence among women and increasing awareness, lipedema remains under-investigated. Ignoring its debilitating nature, surgical treatment for this condition is frequently covered by health insurance only in advanced stages and after the exhaustion of conservative therapies. Methods: A total of 1015 patients with lipedema were recruited via social media platforms. Of these, 860 patients provided answers to at least one complete section of the modified Body-Q questionnaire (response rate 85%). The Mann–Whitney U and Kruskal–Wallis tests were utilized to assess the impact of the surgical treatment by means of patient-reported outcomes on the self-perception of various body areas. Results: The satisfaction scores among conservatively treated patients for abdominal appearance, arms, back, body, buttocks, and inner thighs showed a statistically significant decline with increasing stages of lipedema. The comparison of patient evaluation scores in the appearance domain demonstrated better patient self-perception scores in patients who received at least one session of the surgical treatment for the hips and thighs (p < 0.01), inner thighs (p < 0.01), and excess skin (0.01) scales. On the body scale, the patients who underwent liposuction again reported better satisfaction scores; however, this did not reach statistical significance (p < 0.081). In the health-related quality of life domain, the patients who received liposuction treatment reported a better outcome in the body image (p < 0.01), physical function (p = 0.05), physical symptoms (p = 0.04), and psychological function (p < 0.01) scales. Conclusions: The current study underscores the burden of lipedema of affected patients and its negative impact on self-perception. As the disease progresses, conservatively treated patients experience a decline in satisfaction with various aspects of their appearance. However, surgical interventions, particularly liposuction, does not address esthetic concerns but significantly improve health-related quality of life across multiple domains, emphasizing the comprehensive benefits of surgical intervention in the management of lipedema.

This longitudinal study indicates liposuction is an effective treatment for improving HRQoL and symptoms in lipedema patients, although it may not completely restore HRQoL to normative levels. Limitations include potential selection bias, sampling bias, and the need for longer follow-up. The finding …

Background/Objectives: Lipedema is a chronic, progressive disorder of the adipo-fascial tissue characterized by abnormal subcutaneous fat accumulation, inflammation, fibrosis, pain, and edema. Despite its considerable impact on patients’ quality of life, it remains underdiagnosed. Recent studies have suggested a potential overlap between lipedema and hypermobility spectrum disorders (HSDs), both involving connective tissue dysfunction. This work explores the shared pathophysiological features of lipedema and HSD, highlighting clinical correlations, comorbidities, and the need for integrated diagnostic and therapeutic approaches. Methods: A cross-sectional observational study was conducted through an online survey targeting individuals with lipedema and a control group with lymphedema. The questionnaire assessed symptoms typically associated with HSD, including musculoskeletal, gastrointestinal, urogynecological, vascular, and neuropsychological manifestations. Descriptive statistics were used to evaluate clinical patterns in both groups. Results: Among the lipedema patients, 44% reported joint hypermobility and 60% recalled being hypermobile during childhood. High rates of pediatric overweight (50%), low muscle tone (55%), and exercise-induced fatigue (70%) were observed. Adult symptoms included joint pain (notably in the ankles, knees, cervical spine, sacrum, and feet), digestive issues (50%), and thyroid disorders (24.4%). Compared with the control group, patients with lipedema showed significantly more connective tissue-related motor deficits and systemic symptoms. Conclusions: Connective tissue laxity may play a critical role in the pathogenesis of lipedema, contributing to multisystemic manifestations through vascular, lymphatic, gastrointestinal, and musculoskeletal involvement. The high prevalence of HSD-like features calls for a paradigm shift in the understanding of lipedema as a systemic disorder. Early identification of connective tissue alterations, especially in children with familial predisposition, could enable timely interventions, potentially mitigating disease progression. A multidisciplinary, evidence-based approach is essential for accurate diagnosis and effective management.

Lipedema, historically underrecognized, has recently gained attention due to advancements in research and growing public awareness. The Brazilian Consensus Statement on Lipedema, developed by the Brazilian Society of Angiology and Vascular Surgery, aims to establish clear recommendations for the diagnosis, treatment, and management of lipedema. Using the Delphi methodology, experts elaborated 90 statements about lipedema, which were then evaluated by a panel of 113 professionals. The statements were analyzed using SurveyMonkey, with a 75% agreement threshold required for their inclusion in the consensus statement. Most statements achieved significant consensus, with only 9 topics requiring further investigation. This consensus statement highlights the complexity of lipedema, the effectiveness of conservative treatment over surgery, the need for multidisciplinary approaches, and the importance of awareness to reduce underdiagnosis and stigma. It also underscores the ongoing need for research to develop more effective management strategies.

DiVA portal is a finding tool for research publications and student theses written at the following 50 universities and research institutions.

BACKGROUND: The etiology of lipoedema remains unclear, making diagnosis and treatment challenging. Current treatment primarily consists of general lifestyle recommendations, with effective self-management being essential for integrating these recommendations into daily life. However, no self-management interventions currently address the unique needs of people with lipoedema. This study aimed to develop an evidence-based, theory-informed intervention to enhance self-management in people with lipoedema using the Intervention Mapping (IM) approach. METHODS: Following the first four steps of the IM approach, this study used a participatory methodology involving stakeholders, empirical data, and theory. Steps included: 1) needs assessment; 2) identification of outcomes, performance objectives, and change objectives; 3) selection of behavioural change methods; and 4) development of program components. RESULTS: The resulting intervention includes a program for people with lipoedema and a training program for healthcare professionals (HCPs). The intervention aims to empower patients to engage in self-management and equip HCPs to provide effective support. Key determinants targeted include self-efficacy, self-regulation skills, knowledge, attitudes, and social facilitation. The program for people with lipoedema consists of seven themes aligned with self-management behaviours and is delivered through 19 sessions: seven one-on-one sessions, one session involving supportive individuals, and 11 group sessions. The program for HCPs is delivered through six group sessions, each focusing on the core skills HCPs need to effectively deliver self-management support to their patients. CONCLUSION: The IM approach effectively guided a systematic, transparent, and reproducible development process. Grounded in established theories and behavioural change methods, the intervention provides a strong foundation for implementation and evaluation among people with lipoedema. The fifth and sixth steps of IM are considered future priorities.

Background: Lipedema is a chronic condition characterized by abnormal deposition of subcutaneous adipose tissue, leading to pain. The lack of internationally recognized diagnostic criteria complicates the characterization of pain. Physiological parameters such as pain pressure threshold (PPT) represent promising prognostic markers for diagnosing lipedema, yet they remain understudied. This study aimed to evaluate the reliability and validity of two pain pressure measurements, PPT and the hand-held sphygmomanometer (HHS) in lipedema.Methods: A total of 28 adult females diagnosed with lipedema were recruited. Both PPT, using a digital algometer, and HHS, using a manual aneroid HHS, were performed to assess pain in the lower limbs. The testing was performed in a standing position with PPT and HHS placed on the calf. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) were employed to assess the within session reliability, while the validity between PPT and HHS was analyzed using R2 in a linear regression model.Results: The results showed excellent reliability for both PPT and HHS, with ICC indicating high consistency (ICC = 0.93 to 0.97) and CV showing acceptable scores (CV = 3.62% to 9.06%). In addition, good validity between PPT and HHS was also observed (R2 = 0.69 to 0.74), suggesting that HHS can be a reliable alternative to PPT for pain assessment in lipedema.Conclusion: These findings have important clinical implications, as they expand the knowledge of pain characterization in people with lipedema, potentially aiding in diagnostic refinement. In addition, a cost-effective and accessible method for assessing pain was examined (i.e., HHS), showing promising findings and providing an objective method to help diagnose lipedema.

Liposuction has been shown to be a safe and effective alternative in patients with lipedema. It positively impacts clinical and patient-reported outcomes.