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Lipedema is a chronic disorder affecting women with a 10% incidence worldwide. It is often confused with obesity. This study was undertaken to study microRNAs in lipedema tissue assessed by direct hybridization using the robust n-counter flex DX CE-IVD platform. The mean age of the subjects participating in the study was 40.29 (±12.17). The mean body weight and BMI were 67.37 (±10.02) and 25.75 (±4.10), respectively. The lipedema stages included were I and II. The differential expressed human (hsa)-miRNAs were determined according to a log2 fold-change (LFC) of 0.5 and p value < 0.05. To these, increased expression of hsa-let-7g-5p was evident, as well as reduced levels of hsa-miR-371a-5p, -4454+7975, -365a+b-3p, -205-5p, -196a-5p, -4488, -2116-5p, -141-3p, -208a-3p, -302b-3p, 374a-5p, and -1297. Then, several bioinformatics tools were used to analyze microarray data focusing on validated target genes in silico. KEGG and Gene Ontology (GO) pathway enrichment analysis was conducted. Furthermore, the protein-protein interaction and co-expression network were analyzed using STRING and Cytoscape, respectively. The most upregulated miRNA mainly affected genes related to cell cycle, oocyte meiosis, and inflammatory bowel disease. The downregulated microRNAs were related to endocrine resistance, insulin resistance, hypersensitivity to AGE-RAGEs, and focal adhesion. Finally, we validated by RT-PCR the upregulated hsa-let-7g-5p and two down-regulated ones, hsa-miR-205-5p and hsa-miR-302b-3p, confirming microarray results. In addition, three mRNA target miRNAs were monitored, SMAD2, the target of the hsa-let-7g-5p, and ESR1 and VEGFA, the target of hsa-miR-205-5p and hsa-miR-302b-3p, respectively. Our results open a new direction for comprehending biochemical mechanisms related with the pathogenesis of lipedema, shedding light on this intricate pathophysiological condition that could bring to light possible biomarkers in the future.

The treatment of lipedema remains challenging, largely due to widespread misconceptions. Selecting the appropriate treatment method necessitates the use of accurate outcome measures. This study aims to evaluate the effectiveness of compression therapy combined with exercises versus exercises alone in lipedema patients using various outcome measures. Twenty-four women with lipedema were divided into two equal groups: one group received compression therapy plus exercises while the other group performed exercises only. The effectiveness of the treatment was assessed before and after the intervention using several measures: an SF-36 questionnaire, a symptom severity survey, circumference (via 3D scanning), and body composition analysis. Significant improvements were observed in the SF-36 Physical Functioning and SF-36 Energy/Fatigue scores among participants in the compression group. Additionally, there was a reduction in the heaviness of extremities, the disproportion between the trunk and limbs, and the level of swelling in the compression therapy. Circumferences decreased in both groups. Although more circumferences were significantly reduced in the compression group, the reduction at the point above the knee was greater in the non-compression group. Compression therapy is an effective treatment for lipedema. Various measures, such as quality-of-life questionnaires and symptom severity surveys, can be used as valuable tools for assessing the effectiveness of lipedema treatment.

Background: Lipedema is a disease characterized by an increase in extracellular fluid. In these patients, the increase in the amount of extracellular fluid may accelerate the progression of the disease. The aim of this study is to examine the effect of complex decongestive therapy (CDT) on intracellular/extracellular fluid balance. Methods and Results: Twenty-two female patients diagnosed with lipedema by a specialist lymphologist were included in the study. Patients were subjected to complex decongestive therapy and pneumatic compression therapy 6 days a week for 1 month. Extracellular and intracellular fluid volumes were assessed using bioimpedance spectroscopy before and after the treatment. A decrease in intracellular (p = 0.010) and extracellular (p = 0.002) fluid volumes was observed after the treatment. Conclusion: There is no completely curative treatment method for lipedema. Current treatments aim to slow down the progression of the disease. CDT is considered effective in reducing intracellular and extracellular fluid volume in lipedema patients. Therefore, it is thought to be effective in slowing down the progression of the disease.

AimThis study aimed to monitor public interest in information related to Lipedema and examine potential temporal, seasonal, and income-related trends that may impact public interest.Material – MethodsA dataset was created using the Google Trends tool by inputting the keyword “Lipedema” to obtain the relative search volume (RSV) from 2004 to the present in the United States (US). To examine potential income-related disparities in public interest in Lipedema across the US, RSV values were recorded in the five states with the highest and the lowest median income (Maryland, New Hampshire, New Jersey, Utah, and Washington and Mississippi, West Virginia, Arkansas, New Mexico, Kentucky, respectively).ResultsPublic interest in Lipedema increased significantly over time (R2 = 0.693, p < .001 for the linear trend; R2 = 0.880, p < .001 for the quadratic trend). There were no significant differences between the RSV values between the month of the year and the season of the year (p = 1.000 and p = .859, respectively). RSV values of the five highest-income and low-income states showed significant increases (R2 = 0.333, p < .001, and R2 = 0.195, p < .001, respectively) More rapid growth in interest in Lipedema in states with high income compared to the states with low income (p < .001).ConclusionPublic interest in Lipedema is increasing in both high-income and low-income states. States with higher incomes are more interested. Searches for lipedema are expected to become more frequent, leading to a rising demand for comprehensive education in medical schools and clinician training programs. In addition, there will also be a need for easily accessible, high-quality information resources.

BACKGROUND: Liposuction for stage III lipoedema is a guideline-based but also time-consuming treatment, which can be carried out under specific conditions at the expense of the German statutory health insurance companies (SHI) based on a decision made by the German Federal Joint Committee ("Gemeinsamer Bundesausschuss", G-BA), the highest decision-making body in the German healthcare system, in 09/2019. We postulate that the treatment is not reflected in a cost-covering manner in the university cost system. METHODS: This monocentric, retrospective study examined the economic aspects of 92 cases in 48 lipoedema patients treated during the period from 09/2019 to 08/2023 at the expense of the SHI. These cases were filtered out using DRG coding and the Operation and Procedure Classification system ("Operationen- und Prozedurenschlüssel", OPS), and the costs and revenues per patient were calculated using the data from our internal service accounting. RESULTS: After an inpatient stay of 2.64±1.33 days, the total revenue was € 4,726.79±680.98. This included € 1,532.92±856.99 inpatient costs, € 2,686.02±1,174.70 in operating costs, € 940.76±189.18 in anaesthesia costs and € 63.19±125.38 in other costs that had to be paid within the clinic. On average across all treatments, this resulted in a loss of -€ 875.22 /case. In 54 cases (59%), the costs exceeded the revenue. In total, the calculation of all cases resulted in a loss of € -80,520.63. If medical personnel costs are included, this amount rises to over € 100,000. CONCLUSION: The results show that the surgical treatment of lipoedema in the German DRG and university cost systems is not cost-covering. This could be relevant in the final economic assessment of the G-BA, which may result in an adjustment of the DRG revenue.

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.

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

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.

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

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

Lipohyperplasia dolorosa (LiDo), also known as lipedema, is a painful subcutaneous adipose tissue disorder. While the characteristic bilateral accumulation of adipocytes in extremities sparing hands and feet is investigated, an objective characterization of pain and the sensory system of LiDo patients is missing. Accordingly, progress to overcome the unsatisfying response to pain-therapeutics of patients of this widespread, lifelong, and severe disease is missing. We characterized the sensory detection profile of painful and non-painful stimuli in 20 non-obese LiDo patients and 20 waist-to-height-ratio matched controls using the clinically approved QST-protocol of the German Research Association on Neuropathic Pain (DFNS e.V.). Further, pain-reports and participants’-psychometry was assessed using the German Pain Questionnaire. LiDo patients showed no overt psychometric abnormalities. LiDo pain appeared as somatic rather than neuropathic or psychosomatic aversive. All QST measurements were normal with the selective exception of two: The pressure pain threshold (PPT) was strongly reduced and the vibration detection threshold (VDT) was strongly increased selectively at the affected thigh. In contrast, sensory profiles at the dorsum of the hand were normal. ROC-analysis of the combination of PPT and VDT of thigh versus hand shows high sensitivity and specificity, categorizing correctly 96.5% of the measured participants as LiDo patients or healthy controls, respectively. Thus, we propose to assess both, PPT and VDT, at the painful thigh and the pain-free hand as basis to develop a combined PVTH-score for differential diagnosis as a fast and convenient bedside test for the identification of non-obese LiDo patients.

Lipoedema is the disproportionate accumulation of adipose tissue in the lower body, often associated with hormonal changes in women. Lipoedema is commonly misdiagnosed as lymphoedema or obesity due to similarities in appearance. The aim of this study is to compare body composition and fluid measures of women with lipoedema, lymphoedema, and matched control participants, to determine differences that may help distinguish between each condition. One hundred and eleven participants aged over 18, who presented with the complaint of leg swelling and underwent indocyanine green lymphography were included in this study. Our analysis showed that the individuals with lymphoedema had a significantly higher overall total body water (lymphoedema: 9.6 ± 4.2 L, lipoedema: 7.4 ± 2.3 L, control: 7.5 ± 1.8 L; p < .001) and extracellular fluid (lymphoedema: 4.6 ± 1.6, lipoedema: 3.4 ± 1.0 L, control: 3.5 ± 0.7 L; p < .001) in the legs when compared to individuals with lipoedema and matched control participants. Individuals with lipoedema had a significantly higher overall fat mass as a percentage of body weight when compared to individuals with lymphoedema (lymphoedema: 33.1% ± 9.5%, lipoedema: 39.4% ± 6.5%; p = .003). We are unable to distinguish between individuals with lipoedema and control participants, therefore further research needs to be conducted to help reduce misdiagnosis.

Lower extremity swelling may be broadly characterized as due to edema, lymphedema, or lipedema. Differentiation between these three conditions is important for providing appropriate treatment. This review analyzes and compares different clinical diagnostic modalities for these conditions, with the aim of assisting in the process of choosing the most appropriate diagnostic modality by highlighting the advantages and limitations of each. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for a systematic search of peer-reviewed literature, the following diagnostic methods for lower extremity swelling were investigated: (1) ultrasound (US), (2) lymphoscintigraphy (LSG), (3) computed tomography (CT), (4) bioimpedance spectroscopy (BIS), (5) tissue dielectric constant (TDC), and (6) magnetic resonance imaging (MRI), including magnetic resonance lymphangiography (MRL). The databases used in the search were PubMed, ProQuest, CINAHL Complete, Web of Science, Embase, and Biomedical Reference Collection. After retrieving 115 studies based on predetermined inclusion criteria, a total of 31 studies were critically evaluated. The main results indicate the following: duplex US is the modality of choice to initially identify lower extremity edema such as deep venous thrombosis (DVT) and venous reflux due to its high sensitivity and specificity. CT venography of the lower extremity appears to be the preferred option for gynecologic cancer patients with lower extremity swelling post-treatment, as it measures subcutaneous tissue volumes to look for DVTs, lymphoceles, and cancer recurrence. TDC is a recommended modality for a variety of conditions, including edema and lymphedema, in part, due to its noninvasive localized assessment capabilities and ease of use. LSG emerges as an effective imaging modality for lymphedema characterization with minimal invasiveness and high sensitivity and specificity. BIS is widely used to identify and monitor lower extremity lymphedema but has been reported to have low sensitivity and lacks the ability to account for changes in tissue composition such as fibrosis. US and MRL are favored for lipedema diagnosis, with MRL providing comprehensive anatomical and functional insights, albeit with cost and accessibility limitations compared to US. While CT, MRI, US, and TDC are all useful for differentiating lymphedema from lipedema, MRI is the preferred modality due to its anatomical and functional diagnostic capabilities. However, US is a pragmatic alternative for use with obese patients or when MRI is not an option.

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.

Background: Lipedema is a progressive condition involving excessive deposition of subcutaneous adipose tissue, predominantly in the lower limbs, which severely compromises quality of life. Despite the impact of lipedema, its molecular and genetic bases are poorly understood, making diagnosis and treatment difficult. Historical evaluation of individuals with lipedema indicates a positive family history in 60%-80% of cases; however, genetic investigation of larger family cohorts is required. Here, we report the largest family-based sequencing study to date, aimed at identifying genetic changes that contribute to lipedema. Methods and Results: DNA samples from 31 individuals from 9 lipedema families were analyzed to reveal genetic variants predicted to alter protein function, yielding candidate variants in 469 genes. We did not identify any individual genes that contained likely disease-causing variants across all participating families. However, gene ontology analysis highlighted vasopressin receptor activity, microfibril binding, and patched binding as statistically significantly overrepresented categories for the set of candidate variants. Conclusions: Our study suggests that lipedema is not caused by a single exomic genetic factor, providing support for the hypothesis of genetic heterogeneity in the etiology of lipedema. As the largest study of its kind in the lipedema field, the results advance our understanding of the disease and provide a roadmap for future research aimed at improving the lives of those affected by lipedema.

BACKGROUND: Lipedema is characterized by the painful abnormal deposition of adipose tissue in the lower limbs and is often misdiagnosed as obesity. Considering the numerous bothersome physical symptoms of lipedema, women with lipedema may have greater disability and emotional problems than women with lifestyle-induced obesity. OBJECTIVES: Our study aims to assess disability, anxiety and depression symptoms in women with lipedema compared to women with overweight/obesity. MATERIAL AND METHODS: Women with lipedema (n = 45, with a mean age of 41 years) and women who are overweight/obese (n = 43, with a mean age of 44.95 years) were asked to complete the following questionnaires: The World Health Organization Disability Assessment Schedule (WHO-DAS II), Beck's Depression Inventory - II (BDI-II), and The Hospital Anxiety and Depression Scale (HADS). RESULTS: Despite the higher BMI in the overweight/obesity group, the group with lipedema was more disabled in numerous domains of the WHO-DAS II questionnaire, including Life activities - domestic, work and school responsibilities and Participation in society When the influence of BMI was adjusted, a difference in the domain of Mobility was also present. The study groups did not differ in anxiety and depression symptoms. CONCLUSIONS: We showed that behavioral impairment was the main factor affecting functioning in women with lipedema. Emotional symptoms did not differentiate the study groups. Leg volumes and adipose tissue pain intensity were associated with greater disability in women with lipedema, and should be considered in managing women with this condition and in future research estimating the effectiveness of lipedema treatment.

BACKGROUND: Lipedema is a chronic disease marked by symmetric enlargement of painful nodular and fibrotic adipose tissue, predominantly affecting the limbs. Since there is no specific test or biomarker for this condition, years often pass before the diagnosis of lipedema is established for the first time, thereby causing psychosocial distress, including depression, eating disorders, and social isolation. Over the last few years several advanced Doppler-based technologies have been developed to visualize slow flow blood vessels and superficial microvascular architecture undetectable by traditional color Doppler flow imaging (CDFI). OBJECTIVE: The aim of this study was to evaluate the superficial microvascular anatomy in lipedema patients compared to healthy controls and investigate the clinical significance of the Ultra Micro Angiography (UMA) technology in the diagnosis of lipedema. This new technique may contribute to reduce the diagnostic delay and, eventually, establish and guide treatment strategies toward a better therapeutic outcome in lipedema patients. METHODS: 25 patients with lipedema and ten healthy controls with no history of lipedema were included in this study. All ultrasound examinations were performed on a novel high-performance ultrasound system (Resona R9/Mindray) using CDFI and the UMA technique. RESULTS: In all of the patients, Ultra Micro Angiography achieved the excellent visualization of microvascular structures, revealing that most lipedema patients showed grade 3 (n = 13) or grade 2 (n = 8) flow. UMA was superior to CDFI for depicting the microvascular structures. CONCLUSIONS: Here we show that UMA imaging characterizes the subcutaneous microvasculature with an unprecedented accuracy. The method has the advantage of being sensitive to small, slow-flowing vessels. This allows for the assessment of the course of vessels and vascular pathologies in great detail. Thus, UMA as a non-invasive diagnostic method can improve diagnostic accuracy in lipedema.