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Background: Bioimpedance spectroscopy (BIS) is commonly used for the detection and monitoring of lymphedema and potentially lipedema. BIS measures limb electrical resistance, which decreases with fluid accumulation in these conditions. R0, the index of extracellular fluid and lymph accumulation, is typically estimated using Cole modeling, but technical and biological factors can affect accuracy.Methods: Participants with clinically affirmed bilateral leg lymphedema, lipedema, self-ascribed swelling, and healthy controls were included in this study. Impedance measurements were taken using a stand-on BIS device, and R0 was estimated using both the Cole modeling method and a regression approach. Quality of data fitting was assessed visually and statistically.Results: Control participants were younger and lighter compared with the clinical groups. The regression method was able to analyze 100% of participant data, whereas the Cole method was successful in only 80%–88% of cases in the lymphedema and lipedema groups. Additionally, the regression approach provided better curve fitting accuracy for all participants.Conclusion: The regression method offers a robust alternative for estimating R0 values in BIS data, especially in lower limb assessments where data analysis is challenging. The small difference between methods in absolute R0 values (2.5%) has minimal practical implications, suggesting interchangeability in data analysis. The Cole method showed poorer performance, particularly in participants with lymphedema, possibly due to differences in water proportions and limb size. Overall, the regression method can be effectively used in clinical practice for estimating R0 values in BIS data, offering a more accurate and reliable approach than traditional Cole plotting methods.

Lipoedema is a loose connective tissue disease primarily affecting women characterized by an abnormal build-up of painful fat in the legs and arms. In healthcare, lipoedema is often confused with obesity, and today, diagnostic tools and standardized guidelines for adequate treatments are lacking. Still, research on how affected women manage their health problems and whether they are satisfied with their care remains sparse. Therefore, this study aimed to contribute knowledge on healthcare experiences, and their use and self-reported effects of self-care and treatments among women with lipoedema.

IntroductionLipedema is a chronic and progressive adipose tissue disorder that predominantly affects women. However, despite its high prevalence and severe negative impact on quality of life, it remains significantly underdiagnosed. The aim of this study was to assess the knowledge and awareness of …

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.

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.

<span><b>Background:</b> Lipedema is a subcutaneous adipose tissue disorder mainly affecting women. Its progressive nature often requires high-volume liposuction for efficient pain reduction. However, aspiration volumes of more than 5 L within a single session may lead to a variety of complications. Thus,</span> …

This study explored experienced weight stigma, internalised weight bias and depressive symptom severity in lipoedema, a chronic health condition that primarily affects women and involves painful and disproportionate adipose tissue. This study utilised an international cross-sectional online survey i …

Lipedema is a lipodystrophic disease that is typically characterized by a marked increase in lower-body subcutaneous adipose tissue that is purported to have increased inflammation and fibrosis, impaired microvascular/lymphatic circulation and to be resistant to reduction by weight loss therapy. However, these outcomes have not been adequately studied. We evaluated body composition, insulin sensitivity, metabolic health and adipose tissue biology in women with obesity and lipedema (Obese-LIP) before and after moderate (~9%) diet-induced weight loss. At baseline, people with Obese-LIP had ~23% greater leg fat mass, ~11% lower android-to-gynoid ratio and ~48% greater insulin sensitivity (all P&lt;0.05) than women matched on age, BMI and whole-body adiposity. In Obese-LIP, macrophage content and expression of genes involved in inflammation and fibrosis were greater, whereas lymph/angiogenesis-related genes were lower in thigh than abdominal subcutaneous adipose tissue. Weight loss improved insulin sensitivity and decreased total fat mass, with similar relative reductions in abdominal and leg fat masses, but without changes in markers of inflammation and fibrosis. These results demonstrate that affected adipose tissue in women with lipedema is characterized by increased inflammation and fibrogenesis, and alterations in lymphatic and vascular biology. Moderate diet-induced weight loss improves metabolic function and decreases lower-body adipose tissue mass.

Routine cold-water immersion (CWI) is typically suggested to reduce inflammation, a hallmark property of lipedema. Lipedema is a connective tissue disorder with a genetic component that presents with a disproportionate distribution of nodules in the extremities. This case report explores the impact …

This case report explores the use of radio electric asymmetric conveyor (REAC) technology for chronic pain management, functional limitations, and metabolic dysfunction in a 67-year-old female with rheumatoid arthritis, advanced lipedema, and ...

Background:  Lower limb swelling presents a diagnostic challenge with diverse causes, including well-known issues like venous insufficiency and lymphedema, and less-understood conditions like lipedema. Lipedema, involving abnormal fat accumulation in the lower extremities, is frequently misdiagnosed, posing challenges for affected individuals. This research aimed to report and analyze the clinical features of patients presenting with the complaint of lipedema. Methods:  A retrospective cross-sectional study was conducted in Saudi Arabia from April to November 2023, involving adult patients from a specialized clinic in lipedema and lymphedema management. Data were collected through clinical evaluation and a comprehensive data collection sheet. Results:  In a cohort of 115 female patients (mean age: 38.58), the most common age for disease onset was around 20–29 years. Physical examinations revealed symmetric enlargement (88%), collar sign (43%), orthostatic nonpitting edema (49%), and telangiectasia (64%). Varicose veins were present in 36%, Stemmer signs in 2%, and foot edema in 13%. Clinical diagnosis with lipedema occurred in 71%, with grade 2 (31%) as the most common severity and type 3 (47%) as the prevalent disease type. Conclusions:  The current study, the first of its kind in the Middle East and specifically in Saudi Arabia, emphasizes the urgency of increased awareness and intervention due to a high underdiagnosis rate in lipedema. The observed complexity in symptoms and correlations between severity, lymphatic impairment, and body mass index underscore lipedema’s multifaceted nature. Future research should explore regional and cultural influences and conduct larger studies to validate and recognize various lipedema features.

The validated Dutch translation showed high values for internal consistency, test-retest reliability, and validity, which allows us to implement the questionnaire in the early detection of LEL after gynecological cancer treatment.

<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.

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.

BACKGROUND: Mast cells are immune cells that mediate hypersensi-tivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue di-sorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema. OBJECTIVE: Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema. METHODS: Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spec-trometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks. RESULTS: Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity. CONCLUSION: Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema.

This study aimed to assess the potential benefits of a low-carbohydrate, high-fat (LCHF) diet on body composition, leg volume, and pain reduction in women with lipedema compared to overweight or women with obesity. The study included 113 female participants, 56 with lipedema and 57 with overweight/obesity (BMI >25 kg/m2) without lipedema. All subjects were prescribed a low-carbohydrate, high-fat (LCHF) diet with anti-inflammatory properties to adhere to for a duration of 7 months. Measurements of anthropometry, body weight, composition, and pain (VAS) were conducted at the study’s commencement and conclusion. 52 participants completed the study. Both groups experienced a similar weight reduction, amounting to 12.9% compared to the baseline (−10.8 kg vs. −11.9 kg; p = 0.14, for lipedema and women with overweight/obesity, respectively). The most reduction was in body fat mass. Improvements in various parameters were observed, except for ankle circumferences, which decreased more in the lipedema group. Lipedema participants showed significantly reduced pain levels following the LCHF diet (4.6 ± 2.6 vs 3.0 ± 2.3; ). The LCHF diet holds promise for weight loss, body fat reduction, leg volume management, and pain alleviation in women with lipedema. These findings provide valuable insights into potential therapeutic strategies for lipedema management.

BACKGROUND: National survey data exploring the patient experience with lipedema are lacking. METHODS: We conducted national surveys from 2016 to 2022 of women with lipedema as well as female controls. Surveys collected information on symptomatology, pain, and therapies. We performed logistic regression comparing symptoms among those with lipedema versus controls adjusting for age and BMI. RESULTS: A total of 707 women with lipedema and 216 controls completed the surveys. Those with lipedema had a mean age of 48.6 years and mean BMI of 40.9 kg/m2. Lipedema symptom onset occurred frequently at puberty (48.0%) or pregnancy (41.2%). Compared to controls, women with lipedema were more likely to report leg swelling in heat (odds ratio [OR], 66.82; 95% CI, 33.04-135.12; p < 0.0001), easy bruising (OR, 26.23; 95% CI, 15.58-44.17; p < 0.0001), altered gait (OR, 15.54; 95% CI, 7.58-31.96; p < 0.0001), flu-like symptoms (OR, 12.99; 95% CI, 4.27-39.49; p < 0.0001), joint hypermobility (OR, 12.88; 95% CI, 6.68-24.81; p < 0.0001), cool skin (OR, 12.21; 95% CI, 5.20-28.69; p < 0.0001), varicose veins (OR, 11.29; 95% CI, 6.71-18.99; p < 0.0001), and fatigue (OR, 9.59; 95% CI, 6.10-15.09; p < 0.0001). Additionally, 70.3% had upper arm involvement, 21.2% reported foot swelling, and 16.6% reported foot pain. Most (52.2%) reported no symptom improvement with diet or exercise. Common therapies used included compression therapy (45.0%), gastric bypass (15.7%), and lower-extremity liposuction (14.0%). CONCLUSION: In a large, national, symptom survey, women with lipedema reported excess pain, swelling, and fat in the legs along with numerous symptoms beyond those classically described. Symptom responses to common therapies remain understudied.

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74—a common receptor for both cytokines—was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema.