Venous thromboembolic outcomes in patients with lymphedema and lipedema: An analysis from the National Inpatient Sample.

BACKGROUND: Patients with lymphedema and lipedema share physical exam findings that may lead to misdiagnosis. Poor mobility is common in patients with obesity and patients with lymphedema and lipedema. This may constitute a risk factor for venous thromboembolism (VTE). Our objective was to evaluate the association of VTE in obese patients with lymphedema and lipedema. METHODS: The National Inpatient Sample (NIS) was searched from 2016 to 2020 to identify hospital admissions of obese female patients with lymphedema and lipedema. Patients were analyzed in the context of presence or absence of VTE while adjusting for complex cluster sampling techniques. Predictors of VTE were accessed by multivariable regression. RESULTS: Lymphedema was identified in 189,985 patients and lipedema in 50,645 patients. VTE was observed in 3.12% (n = 374,210) of patients with obesity. In patients with obesity, VTE was more common in patients with lymphedema than without (2.6% vs 1.6%; p < 0.01). Similarly, VTE was more common in patients with lipedema than without (0.6% vs 0.4%; p < 0.01). After multivariable logistic regression, VTE events in obese patients with lymphedema were higher versus without (OR 1.6; CI 1.08-2.43; p = 0.02). Similarly, VTE events were more common in obese patients with lipedema versus obese patients without lipedema (OR 1.20; CI 1.03-1.41; p = 0.02). CONCLUSIONS: In this hypothesis-generating study, lymphedema and lipedema show a positive association with VTE after adjusting for baseline patient characteristics such as obesity, which is a known independent risk factor for VTE. Mechanisms whereby lymphedema and lipedema are associated with VTE should be investigated.

National survey of patient symptoms and therapies among 707 women with a lipedema phenotype in the United States.

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.

Screening for Peripheral Vascular Stiffness in Lipedema Patients by Automatic Electrocardiogram-Based Oscillometric Detection.

Body mass index (BMI) is seen as a predictor of cardiovascular disease (CVD) in lipedema patients. A valid predictor of CVD is increased aortic stiffness (IAS), and previous research described IAS in lipedema. However, it is not known if this applies to all patients. In this cross-sectional single-center cohort study, peripheral pulse wave velocity (PWV) as a non-invasive indicator of aortic stiffness was measured in 41 patients with lipedema, irrespective of stage and without pre-existing cardiovascular conditions or a history of smoking and a maximum body mass index (BMI) of 35 kg/m2. Automatically electrocardiogram-triggered oscillometric sensor technology by the Gesenius-Keller method was used. Regardless of the stage of lipedema disease, there was no significant difference in PWV compared to published standard values adjusted to age and blood pressure. BMI alone is not a predictor of cardiovascular risk in lipedema patients. Measuring other anthropometric factors, such as the waist-hip ratio or waist-height ratio, should be included, and the existing cardiovascular risk factors, comorbidities, and adipose tissue distribution for accurate risk stratification should be taken into account. Automated sensor technology recording the PWV represents a valid and reliable method for health monitoring and early detection of cardiovascular risks.

Observational Study on a Large Italian Population with Lipedema: Biochemical and Hormonal Profile, Anatomical and Clinical Evaluation, Self-Reported History.

We analyzed the medical condition of 360 women affected by lipedema of the lower limbs in stages 1, 2, and 3. The data were assessed for the whole population and compared between different clinical stages, distinguishing between obese and non-obese patients. The most frequent clinical signs were pain when pinching the skin, subcutaneous nodules, and patellar fat pads. The most frequently painful site of the lower limbs was the medial lower third of the thigh. The pain score obtained on lower limb points increased progressively with the clinical stage. In all points evaluated, the thickness of the subcutaneous tissue increased with the clinical stage. Analyzing the data on the lower medial third of the leg and considering only patients with type 3 lipedema, the difference between stages was statistically significant after correction for age and BMI. We found higher levels of C-reactive protein at more severe clinical stages, and the difference was significant after correction for age and BMI between the stages. Overall, the prevalence of alterations of glucose metabolism was 34%, with a progressive increase in prevalence with the clinical stage. The most frequent comorbidities were vitamin D insufficiency, chronic venous disease, allergies, dyslipidemia, headache, and depression of mood. Interestingly, in comparison with the general population, we found higher prevalence of chronic autoimmune thyroiditis and polycystic ovary syndrome. Finally, the clinical stage and the involvement of the upper limbs or obesity suggest a worse clinical, anthropometric, and endocrine-metabolic profile.

National Lymphoedema Conference 2024: session summaries.

The 11th annual National Lymphoedema Conference, organised by the British Journal of Community Nursing in association with the British Lymphology Society and Lipoedema UK, was hosted at the America Square Conference Centre, London, on 22 February 2024. The conference, which aims to provide new insights into the latests developments in lymphoedema care and management through talks by leading experts in the field, was attended by an impressive number of delegates and exhibitors. The sessions were Chaired by BLS Trustee Rebecca Elwell, and are summarised below.

Subcutaneous Adipose Tissue Edema in Lipedema Revealed by Noninvasive 3T MR Lymphangiography.

BACKGROUND: Lipedema exhibits excessive lower-extremity subcutaneous adipose tissue (SAT) deposition, which is frequently misidentified as obesity until lymphedema presents. MR lymphangiography may have relevance to distinguish lipedema from obesity or lymphedema. HYPOTHESIS: Hyperintensity profiles on 3T MR lymphangiography can identify distinct features consistent with SAT edema in participants with lipedema. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: Participants (48 females, matched for age [mean = 44.8 years]) with lipedema (n = 14), lipedema with lymphedema (LWL, n = 12), cancer treatment-related lymphedema (lymphedema, n = 8), and controls without these conditions (n = 14). FIELD STRENGTH/SEQUENCE: 3T MR lymphangiography (nontracer 3D turbo-spin-echo). ASSESSMENT: Review of lymphangiograms in lower extremities by three radiologists was performed independently. Spatial patterns of hyperintense signal within the SAT were scored for extravascular (focal, diffuse, or not apparent) and vascular (linear, dilated, or not apparent) image features. STATISTICAL TESTS: Interreader reliability was computed using Fleiss Kappa. Fisher's exact test was used to evaluate the proportion of image features between study groups. Multinomial logistic regression was used to assess the relationship between image features and study groups. The odds ratio (OR) and 95% confidence interval (CI) of SAT extravascular and vascular features was reported in groups compared to lipedema. The threshold of statistical significance was P < 0.05. RESULTS: Reliable agreement was demonstrated between three independent, blinded reviewers (P < 0.001). The frequency of SAT hyperintensities in participants with lipedema (36% focal, 36% diffuse), LWL (42% focal, 33% diffuse), lymphedema (62% focal, 38% diffuse), and controls (43% focal, 0% diffuse) was significantly distinct. Compared with lipedema, SAT hyperintensities were less frequent in controls (focal: OR = 0.63, CI = 0.11-3.41; diffuse: OR = 0.05, CI = 0.00-1.27), similar in LWL (focal: OR = 1.29, CI = 0.19-8.89; diffuse: OR = 1.05, CI = 0.15-7.61), and more frequent in lymphedema (focal: OR = 9.00, CI = 0.30-274.12; diffuse: OR = 5.73, CI = 0.18-186.84). DATA CONCLUSION: Noninvasive MR lymphangiography identifies distinct signal patterns indicating SAT edema and lymphatic load in participants with lipedema. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Deep learning for standardized, MRI-based quantification of subcutaneous and subfascial tissue volume for patients with lipedema and lymphedema.

OBJECTIVES: To contribute to a more in-depth assessment of shape, volume, and asymmetry of the lower extremities in patients with lipedema or lymphedema utilizing volume information from MR imaging. METHODS: A deep learning (DL) pipeline was developed including (i) localization of anatomical landmarks (femoral heads, symphysis, knees, ankles) and (ii) quality-assured tissue segmentation to enable standardized quantification of subcutaneous (SCT) and subfascial tissue (SFT) volumes. The retrospectively derived dataset for method development consisted of 45 patients (42 female, 44.2 ± 14.8 years) who underwent clinical 3D DIXON MR-lymphangiography examinations of the lower extremities. Five-fold cross-validated training was performed on 16,573 axial slices from 40 patients and testing on 2187 axial slices from 5 patients. For landmark detection, two EfficientNet-B1 convolutional neural networks (CNNs) were applied in an ensemble. One determines the relative foot-head position of each axial slice with respect to the landmarks by regression, the other identifies all landmarks in coronal reconstructed slices using keypoint detection. After landmark detection, segmentation of SCT and SFT was performed on axial slices employing a U-Net architecture with EfficientNet-B1 as encoder. Finally, the determined landmarks were used for standardized analysis and visualization of tissue volume, distribution, and symmetry, independent of leg length, slice thickness, and patient position. RESULTS: Excellent test results were observed for landmark detection (z-deviation = 4.5 ± 3.1 mm) and segmentation (Dice score: SCT = 0.989 ± 0.004, SFT = 0.994 ± 0.002). CONCLUSIONS: The proposed DL pipeline allows for standardized analysis of tissue volume and distribution and may assist in diagnosis of lipedema and lymphedema or monitoring of conservative and surgical treatments. KEY POINTS: • Efficient use of volume information that MRI inherently provides can be extracted automatically by deep learning and enables in-depth assessment of tissue volumes in lipedema and lymphedema. • The deep learning pipeline consisting of body part regression, keypoint detection, and quality-assured tissue segmentation provides detailed information about the volume, distribution, and asymmetry of lower extremity tissues, independent of leg length, slice thickness, and patient position.

Stages of lipoedema: experiences of physical and mental health and health care.

PURPOSE: Lipoedema is a progressive adipose (fat) disorder, and little is known about its psychological effect. This study aimed to determine the experiences of physical and mental health and health care across stages of lipoedema. METHODS: Cross-sectional, secondary data from an anonymous survey (conducted 2014-2015) in Dutch and English in those with self-reported lipoedema were used (N = 1,362, Mdnage = 41-50 years old, 80.2% diagnosed). χ2 analyses of categorical data assessed lipoedema stage groups 'Stage 1-2' (N = 423), 'Stages 3-4' (N = 474) and 'Stage Unknown' (N = 406) experiences of health (physical and psychological), and health care. RESULTS: Compared to 'Stage 1-2', 'Stage 3-4' reported more loss of mobility (p = < .001), pain (p = < .001), fatigue (p = .002), problems at work (p = < .001) and were seeking treatment to improve physical functioning (p = < .001) more frequently. 'Stage 3-4' were more likely to report their GP did not have knowledge of lipoedema, did not take them seriously, gave them diet and lifestyle advice, dismissed lipoedema, and treated them 'badly' due to overweight/lipoedema compared to 'Stage 1-2' (p = < .001). 'Stage 3-4' were more likely to report depression (p = < .001), emotional lability (p = .033) eating disorders (p = .018) and feeling lonelier, more fearful, and stayed at home more (p = < .001) and less likely to have visited a psychologist (p = < .001) compared to 'Stage 1-2'. CONCLUSIONS: A divergent pattern of physical and psychological experiences between lipoedema stages reflects physical symptom differences and differences in psychological symptoms and health care experiences. These findings increase the understanding of lipoedema symptoms to inform psychological supports for women with lipoedema in navigating chronic health care management.

Assessment of lipoedema awareness among polish women- online survey study.

BACKGROUND: Lipoedema is an adipose tissue disorder that is still not fully understood. The primary purpose of this study is to explore the state of knowledge and understanding of lipoedema among Polish women. The secondary aim is to investigate the possible association between knowledge and factors such as BMI, self-reported symptoms, and age. METHODS: One hundred seventy polish women took part in an online survey study that was posted to social media groups and forums in January 2022. The survey consisted of 12 questions and aimed at assessing the basic knowledge about lipoedema. RESULTS: The least proportion of participants (4%) could correctly indicate the methods of lipoedema treatment. The accurate definition of lipoedema was indicated only by 7% of women, 12% identified characteristic features of lipoedema, and 37% correctly evaluated lipoedema curability. The greatest proportion of respondents knew the differences between obesity and lipoedema (50%). CONCLUSIONS: Awareness of lipoedema among women is deficient. A significant proportion of the respondents report the occurrence of lipoedema symptoms. In order to improve the situation of lipoedema patients, it is crucial to increase the knowledge about this condition both among medical professionals and the general public.

Serum Metabolomic Profiling of Patients with Lipedema.

Lipedema is a chronic condition characterized by disproportionate and symmetrical enlargement of adipose tissue, predominantly affecting the lower limbs of women. This study investigated the use of metabolomics in lipedema research, with the objective of identifying complex metabolic disturbances and potential biomarkers for early detection, prognosis, and treatment strategies. The study group (n = 25) comprised women diagnosed with lipedema. The controls were 25 lean women and 25 obese females, both matched for age. In the patients with lipedema, there were notable changes in the metabolite parameters. Specifically, lower levels of histidine and phenylalanine were observed, whereas pyruvic acid was elevated compared with the weight controls. The receiver operating characteristic (ROC) curves for the diagnostic accuracy of histidine, phenylalanine, and pyruvic acid concentrations in distinguishing between patients with lipedema and those with obesity but without lipedema revealed good diagnostic ability for all parameters, with pyruvic acid being the most promising (area under the curve (AUC): 0.9992). Subgroup analysis within matched body mass index (BMI) ranges (30.0 to 39.9 kg/m2) further revealed that differences in pyruvic acid, phenylalanine, and histidine levels are likely linked to lipedema pathology rather than BMI variations. Changes in low-density lipoprotein (LDL)-6 TG levels and significant reductions in various LDL-2-carried lipids of patients with lipedema, compared with the lean controls, were observed. However, these lipids were similar between the lipedema patients and the obese controls, suggesting that these alterations are related to adiposity. Metabolomics is a valuable tool for investigating lipedema, offering a comprehensive view of metabolic changes and insights into lipedema's underlying mechanisms.

A Comparative Analysis to Dissect the Histological and Molecular Differences among Lipedema, Lipohypertrophy and Secondary Lymphedema.

Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an insufficient understanding of the conditions and particularly of lipohypertrophy. In our study, we performed histological and molecular analysis in anatomically-, BMI- and gender-matched samples of lipedema, lipohypertrophy and secondary lymphedema versus healthy control patients. Hereby, we found a significantly increased epidermal thickness only in patients with lipedema and secondary lymphedema, while significant adipocyte hypertrophy was identified in both lipedema and lipohypertrophy. Interestingly, the assessment of lymphatic vessel morphology showed significantly decreased total area coverage in lipohypertrophy versus the other conditions, while VEGF-D expression was significantly decreased across all conditions. The analysis of junctional genes often associated with permeability indicated a distinct and higher expression only in secondary lymphedema. Finally, the evaluation of the immune cell infiltrate verified the increased CD4+ cell and macrophage infiltration in lymphedema and lipedema respectively, without depicting a distinct immune cell profile in lipohypertrophy. Our study describes the distinct histological and molecular characteristics of lipohypertrophy, clearly distinguishing it from its two most important differential diagnoses.

Enhanced Angiogenesis in HUVECs Preconditioned with Media from Adipocytes Differentiated from Lipedema Adipose Stem Cells In Vitro.

Lipedema is a connective tissue disorder characterized by increased dilated blood vessels (angiogenesis), inflammation, and fibrosis of the subcutaneous adipose tissue. This project aims to gain insights into the angiogenic processes in lipedema using human umbilical vein endothelial cells (HUVECs) as an in vitro model. HUVECs were cultured in conditioned media (CM) collected from healthy (non-lipedema, AQH) and lipedema adipocytes (AQL). The impacts on the expression levels of multiple endothelial and angiogenic markers [CD31, von Willebrand Factor (vWF), angiopoietin 2 (ANG2), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMPs), NOTCH and its ligands] in HUVECs were investigated. The data demonstrate an increased expression of CD31 and ANG2 at both the gene and protein levels in HUVECs treated with AQL CM in 2D monolayer and 3D cultures compared to untreated cells. Furthermore, the expression of the vWF, NOTCH 4, and DELTA-4 genes decreased. In contrast, increased VEGF, MMP9, and HGF gene expression was detected in HUVECs treated with AQL CM cultured in a 2D monolayer. In addition, the results of a tube formation assay indicate that the number of formed tubes increased in lipedema-treated HUVECs cultured in a 2D monolayer. Together, the data indicate that lipedema adipocyte-CM promotes angiogenesis through paracrine-driven mechanisms.

Breaking the circle-effectiveness of liposuction in lipedema.

BACKGROUND: Lipedema is a common chronic fat distribution disorder often aligned with pain and reduced quality of life affecting 6-10% of the female population. Although lipedema has acquired more scientific attention in the last decade, validated diagnosis and treatment still remain challenging for specialists. PATIENTS AND METHODS: In this article we evaluate the effect of liposuction on appearance, pain and coexisting diseases of 860 patients with lipedema. Comparison among stages of lipedema pre- and post-liposuction was performed by using t-Tests for independent samples and Kruskal-Wallis-Tests. RESULTS: Our study demonstrates the positive effect on pain reduction in patients with lipedema after liposuction (NRS 2.24) compared with pre-liposuction pain perception (NRS 6.99) and pain perception of patients with conservative treatment (NRS 6.26). Significant differences were shown in the perception between the stages of lipedema and in the reduction of pain perception by liposuction. Furthermore we examined co-diseases in patients with lipedema, primarily menstruation complaints (43%), sleeplessness (36%) and migraine (35%). CONCLUSIONS: A progress of lipedema disease leads not only to a change of appearance and proportion but also to a progressive increase of pain. Liposuction shows a significant effect on pain reduction -independent of the patients' stage of lipedema.

Surgical lymphology. Therapy option for lymphoedema and lipohyperplasia dolorosa.

The typical therapy in lymphology is conservative. However, reconstructive and resective treatments for primary and secondary lymphoedema as well as resective procedures for lipohyperplasia dolorosa (LiDo) "lipedema" have been available for several decades. Each of these procedures has its clear indication and decades of successful history. These therapies represent a paradigm shift in lymphology. In reconstruction, the basic idea is to restore lymph flow, to bypass the obstacle to drainage in the vascular system. The combination procedures of two-stage application of resection and reconstruction in lymphoedema are just as much a "work in progress" as the concept of prophylactic lymphatic venous anastomosis (LVA). In the case of resective procedures, the focus is not only on improving the silhouette, but also on reducing the complex decongestion therapy (CDT) and - in the case of LiDo - freedom from pain by improving imaging procedures and the early use of surgical therapy options, the development of higher stages of lymphoedema should be a thing of the past. For LiDo, the application of surgical procedures avoids lifelong CDT and achieves painlessness. All surgical procedures, but especially the resection procedures, are now possible in a way that is gentle on the lymphatic vessels and should be offered to patients with lymphoedema or lipohyperplasia dolorosa without reservation if the goals - reduction in circumference, avoidance of lifelong CDT and, in the case of LiDo, painlessness - cannot be achieved by other means.

Body mass index vs. waist-to-height-ratio in patients with lipohyperplasia dolorosa (vulgo lipedema).

BACKGROUND: Lipedema, also known as lipohyperplasia dolorosa (LiDo), is a painful condition affecting women, causing a disproportionate accumulation of subcutaneous adipose tissue in the extremities. It carries a lower risk of diabetes and cardio-metabolic dysfunctions compared to obesity, but coincident obesity can complicate diagnosis and treatment. PATIENTS AND METHODS: This retrospective study included 607 female LiDo patients, ≥ 18 years, stage 1-3, from Germany, the UK, and Spain. Data were collected as part of the standard initial assessment for LiDo patients. RESULTS: Based on waist-to-height-ratio (WHtR), 15.2% of patients were underweight, 45.5% normal weight, 22.1% overweight and 17.3% obese. There was a significant association between WHtR category and age group. Body mass index (BMI) is often overestimated, leading to misdiagnosis of obesity. CONCLUSIONS: The use of BMI also affects the recent decision of the German Federal Joint Committee on the reimbursement of liposuction costs by health insurance funds. Patients with BMI of more than 40 kg/m2 are excluded from cost coverage, and those with BMI between 35 kg/m2 and 40 kg/m2 must first receive conservative obesity therapy. In conclusion, the sole use of BMI in lipedema is unreliable and, in contrast to WHtR, leads to inaccurate diagnoses overestimating overweight and obesity.

[Microcannular liposuction in tumescent anesthesia in lipedema patients: an analysis of 519 liposuctions]. / Mikrokannuläre Liposuktion in Tumeszenzanästhesie beim Lipödem: Eine Analyse von 519 Liposuktionen.

This is a retrospective analysis of all lipedema patients treated by tumescent liposuction at our department in the years 2007-2021: We performed 519 liposuctions in 178 patients with a mean age of 45 ± 15.5 years. By the stage of lipedema the mean age increased significantly, what underlines the concept of lipedema as a chronic progressive disorder. Three-thirds of patients reported at least one comorbidity. The most common were arterial hypertension (32.58%), obesity (24.16%), and hypothyroidism (20.79%). We removed a mean lipoaspirate volume of 4905 ± 2800 mL. A major target for treatment is pain reduction. All patients reported at least a 50% pain reduction after liposuction, while 96 achieved a pain reduction ≥ 90%. The pre-operative pain intensity (p = 0.000) and the lipedema stage (p = 0.032) exerted a significant impact on absolute pain reduction. There was no association of pain reduction to volume loss. The post-operative rate of adverse events was 2.89%. Liposuction in tumescent anesthesia is an effective and safe method to reduce both pain and volume in patients with lipedema.

Lipoedema: a neglected area of women's health.

Lipoedema is an adipose tissue disorder almost exclusively affecting women. Evidence shows lipoedema is both poorly recognised and misdiagnosed which results in many women struggling to get a diagnosis and to gain access to specialist NHS services. This article aims to raise awareness of lipoedema and highlight the main role that community and primary care nurses can play in identifying this long-term condition earlier. It provides detail on the condition to help signpost, refer for diagnosis and initiate conservative management for those individuals with this challenging condition.

Key signaling networks are dysregulated in patients with the adipose tissue disorder, lipedema.

OBJECTIVES: Lipedema, a poorly understood chronic disease of adipose hyper-deposition, is often mistaken for obesity and causes significant impairment to mobility and quality-of-life. To identify molecular mechanisms underpinning lipedema, we employed comprehensive omics-based comparative analyses of whole tissue, adipocyte precursors (adipose-derived stem cells (ADSCs)), and adipocytes from patients with or without lipedema. METHODS: We compared whole-tissues, ADSCs, and adipocytes from body mass index-matched lipedema (n = 14) and unaffected (n = 10) patients using comprehensive global lipidomic and metabolomic analyses, transcriptional profiling, and functional assays. RESULTS: Transcriptional profiling revealed >4400 significant differences in lipedema tissue, with altered levels of mRNAs involved in critical signaling and cell function-regulating pathways (e.g., lipid metabolism and cell-cycle/proliferation). Functional assays showed accelerated ADSC proliferation and differentiation in lipedema. Profiling lipedema adipocytes revealed >900 changes in lipid composition and >600 differentially altered metabolites. Transcriptional profiling of lipedema ADSCs and non-lipedema ADSCs revealed significant differential expression of >3400 genes including some involved in extracellular matrix and cell-cycle/proliferation signaling pathways. One upregulated gene in lipedema ADSCs, Bub1, encodes a cell-cycle regulator, central to the kinetochore complex, which regulates several histone proteins involved in cell proliferation. Downstream signaling analysis of lipedema ADSCs demonstrated enhanced activation of histone H2A, a key cell proliferation driver and Bub1 target. Critically, hyperproliferation exhibited by lipedema ADSCs was inhibited by the small molecule Bub1 inhibitor 2OH-BNPP1 and by CRISPR/Cas9-mediated Bub1 gene depletion. CONCLUSION: We found significant differences in gene expression, and lipid and metabolite profiles, in tissue, ADSCs, and adipocytes from lipedema patients compared to non-affected controls. Functional assays demonstrated that dysregulated Bub1 signaling drives increased proliferation of lipedema ADSCs, suggesting a potential mechanism for enhanced adipogenesis in lipedema. Importantly, our characterization of signaling networks driving lipedema identifies potential molecular targets, including Bub1, for novel lipedema therapeutics.

Indocyanine green lymphography as novel tool to assess lymphatics in patients with lipedema.

OBJECTIVE: Lipedema is a chronic and progressive disease associated with lymphatic impairment at later stages. The aim of our study was to describe the functional status and anatomy of lower limb superficial lymphatic system using indocyanine green (ICG) lymphography in patients with lipedema. METHODS: Following ICG injection at the dorsum of the foot, distance (cm) covered by the dye at 10 (T10') and 25 min (T25') was measured and normalized for limb length. If the dye did not reach the groin within 25 min, patients were classified as "drainage-needing" group (DNG). Values of fat and lean distribution assessed by dual-energy X-ray absorptiometry were extracted, and correlation analysis was performed. Furthermore, anatomical patterns of superficial lymphatics were assessed. RESULTS: Overall, 45 women were included, 25 (56%) of whom were classified as DNG. Symptoms duration was significantly associated with DNG status at multivariate analysis (odds ratio 1.07; 95% CI 1.01-1.14; p = 0.047). Moreover, Spearman's analysis showed a negative correlation between symptoms duration and T25' dye migration (r = -0.469; p = 0.037). Overall, no major anatomical lymphatic changes were found. CONCLUSIONS: Present study suggests that lymphatic functioning in patients with lipedema correlates with symptoms duration. Further research on larger cohorts should verify our findings and clarify their potential therapeutic implications. Overall, ICG lymphography may be promising technique to assess both lymphatic anatomy and functioning in patients with lipedema.

Women with lipoedema: a national survey on their health, health-related quality of life, and sense of coherence.

BACKGROUND: Lipoedema is a chronic disease in adipose tissue that almost exclusively affects women during periods of hormonal alterations. Its main symptoms include an abnormal accumulation of subcutaneous fat in the buttock, hips, and legs, which is associated with pain, swelling, and easy bruising. Herein, a grading in three stages is used to determine disease progression. Problematically, lipoedema manifestations are often confused with lifestyle-induced obesity, which is why the various health problems among affected women often remain unrecognized. Overall, research on lipoedema is scarce. As such, this study examined the health, health-related quality of life (HRQOL), and sense of coherence (SOC) among women with lipoedema. METHODS: We conducted a national cross-sectional study using an online survey assessing sociodemographic data, lipoedema characteristics, symptom severity, comorbidities, HRQOL (RAND-36), and SOC (SOC-13). In total, 245 women with lipoedema, recruited from all Lipoedema Association groups in Sweden, participated. Data were compiled with descriptive statistics, and mean differences between groups were analysed by using parametric and non-parametric tests. RESULTS: Moderate and severe leg heaviness, pain, numbness, cold skin, feeling cold, easy bruising, and sleep problems were found to occur in all lipoedema stages. Moreover, almost all participants reported having comorbidities. Worse physical health and most substantial limitations in daily life were reported among women with the most progressive lipoedema (i.e., stage 3). Social and emotional functioning and SOC were found to be, on the other hand, primarily related to respondents' sociodemographic data and their ages at lipoedema onset. Even though approximately 70% of the women had experienced lipoedema onset before age 30, only three (1.6%) had been diagnosed by a healthcare professional before that age. CONCLUSION: Having lipoedema is associated with several health problems and a lower HRQOL. In addition, the extent of delay in diagnosis within this sample indicates that many women with lipoedema are often underdiagnosed and are left without support from healthcare. These findings call for the need for greater attention on lipoedema. Moreover, further studies on how women with lipoedema manage their health and symptoms, as well as on their experiences of healthcare services and lipoedema treatments, are needed.