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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, …

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.

SUMMARY OBJECTIVE: Chronic edema in the lower extremities leads to significant negative effects on the quality of life, body image perception, satisfaction, self-confidence, and self-esteem of affected individuals. The aim of this study was to evaluate body image, quality of life, and related factors in patients with chronic lower extremity edema due to lymphedema and lipedema. METHODS: This cross-sectional study included 14 lymphedema and 12 lipedema patients receiving treatment at the lymphedema unit. Individuals aged 18–65 years with a confirmed diagnosis were enrolled; those with active infections, malignancies, or systemic diseases were excluded. Body image, dysfunctional thoughts about appearance, and quality of life were evaluated using the Body Cathexis Scale, Beliefs About Appearance Scale, and Lymphedema Quality of Life scale. Circumference measurements of the lower extremities were taken before and after 20 sessions of manual lymphatic drainage therapy. Quantitative data were analyzed to compare the two groups and assess correlations between clinical and psychosocial parameters. RESULTS: No significant differences were observed between the lymphedema and lipedema groups in terms of age, body mass index, or pre-treatment Body Cathexis Scale, Beliefs About Appearance Scale, and Lymphedema Quality of Life scale scores (p>0.05). After 20 sessions of manual lymphatic drainage therapy, both groups showed reductions in limb circumference measurements (p<0.05). Reductions in limb size were moderately associated with improvements in Body Cathexis Scale and Lymphedema Quality of Life scale scores (p<0.05). Post-treatment improvements in body image and quality of life scores were observed in both groups. CONCLUSIONS: This study highlights that patients with lower extremity lymphedema and lipedema experience significant body image disturbances and reduced quality of life. Manual lymphatic drainage therapy improves limb circumference, body image, and quality of life.

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The Ketogenic Diet (KD) is currently the most widely studied nutritional approach for patients with lipedema, although its use may cause important drawbacks especially in case of comorbidities. A Modified Mediterranean Diet (MMed) is more easily adaptable, better tolerated, and can be temporarily replaced by a ketogenic diet for a short period of time if necessary using a sort of "sandwich" approach. We report 10 clinical cases with lipedema and comorbidities subjected to a hypocaloric MMed for 6 months. All patients were properly assessed by anthropometric measurements and body composition before and at the end of nutritional treatment. Only 2 patients needed a short period of KD due to poor response to MMed. At the end of 6-month follow-up, patients showed weight loss with reduction in body circumferences and improvement in body composition. In the two cases where it was necessary to resort to a period of KD, good results were achieved allowing a return to the MMed for the maintenance. In patients suffering from lipedema with associated comorbidities and concomitant pharmacological treatments, the use of MMed as first line treatment allows achievement of better metabolic balance, greater compliance, and improved body composition.

Lipedema is characterized by symmetrical accumulation of subcutaneous fat in the lower and upper limbs, sparing the trunk, feet and hands. Although diagnosis is primarily clinical, ultrasound has proven to be a valuable, non-invasive, reproducible, and cost-effective tool for the assessment of lipedema. Ultrasound (US) facilitates diagnosis through quantitative evaluation of subcutaneous tissue thickness and enables qualitative Lipedema Dermal and Hypodermal Classification (LDHC), with morphological changes. The presence of hyperechoic nodules in patients with lipedema has been previously described and classified as LDHC 3; recently, a case report analyzing the microscopic features of such nodules demonstrated hemorrhagic areas and steatonecrosis, resulting from disorganized hypodermal expansion leading to increased pressure within the subcutaneous compartment—causing hypoxia and stimulating immature neovascularization (fragile wall, predisposing to hemorrhage). However, these nodules are not uniform and exhibit different morphologies, enabling subclassification. The first type presents with poorly defined margins; the second is well-defined margins; the third has an anechoic area, and the fourth shows a faint posterior shadow. These different nodule presentations in lipedema may be correlated with evolutionary stages or previously described clinical presentations, requiring future correlation with pathological anatomy or other diagnostic methods.

This study aims to present the results and limitations of surgery for lower limb lipoedema and lymphedema in a resource-limited surgical setting. This was a cross-sectional, analytical, prospective, in-hospital study covering 15 years. We surgically treated 119 patients, including 18 with lipoedema (15.1%), 69 with stage 2 lymphedema (57.9%), and 32 with elephantiasis (26.9%). We included 81 women (68%) and 38 men (31.9%). The majority (57.7%) of patients with lymphedema were between 30 and 49 years of age. Plastic and excisional surgery was performed in 42.2% of patients with stage 2 lymphedema and in 87.5% with stage 3 (elephantiasis). Lipoedema surgery consisted primarily of liposuction (77.7%). No lymphatic network reconstruction was performed. Our results, at 2 years' post-surgery, were very satisfactory, with limb symmetry in 83.3% of patients operated on for lipoedema, in 84.2% of patients operated on for stage 2 lymphedema, and in 85% of patients operated on for elephantiasis. Surgery for lower limb lipoedema, lymphedema, and elephantiasis is feasible in a resource-limited setting, although challenges remain. The lack of lymphatic network reconstruction constitutes our limitations. Microsurgery is necessary for optimal results.