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As awareness increases about this condition of abnormal fat, so too does interest in how to treat it.

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.

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.

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.

INTRODUCTION: Lipedema is a common, yet underdiagnosed, subcutaneous adipose tissue (SAT) disorder. The main characteristics are SAT expansion in the lower extremities and arms, pain, and tenderness to palpation. It remains unknown if a low-carbohydrate diet (LCD) influences SAT in females with lipedema. OBJECTIVES: To evaluate the effect of a LCD low-energy diet, compared to a low-fat isoenergetic control diet, on calf subcutaneous adipose tissue area, muscle area, SAT/muscle ratio, calf circumference and body composition in females with lipedema. SUBJECTS/METHODS: Adult females with obesity and lipedema were randomized to 1,200 kcal/day diets, either LCD or control (75 and 180 g/day of carbohydrates, respectively) for 8 weeks. Body composition was measured with bioelectrical impedance analysis, calf SAT area, muscle area, and circumference with magnetic resonance imaging and pain with brief pain inventory, before and after the intervention. RESULTS: Thirteen participants were included (five in the LCD group), with a mean age of 46 ± 12 years and a BMI of 37 ± 6 kg/m2. A significant reduction in calf SAT area, calf circumference, and pain was observed in the LCD group only. Both LCD and control groups experienced a significant reduction body weight, fat mass, fat free mass, and muscle area, with no differences between groups. No significant changes over time were found for SAT/muscle ratio. CONCLUSION: A LCD has the potential to reduce SAT and pain in females with lipedema, despite a reduction in muscle mass in lipedema affected areas in both diet groups. Further studies are needed to confirm these findings and explore potential mechanisms. CLINICAL TRIAL REGISTRATION: NCT04632810: Effect of ketosis on pain and quality of life in patients with lipedema (Lipodiet). https://clinicaltrials.gov/study/NCT04632810.

Dr. Allen and Dr. Hines pioneered and first described lipedema in the 1940s, a common subcutaneous adipose tissue disorder characterized by enlargement of both lower extremities. Lipedema is not edema; it is a genetically determined disturbance in adipose tissue mass and adipose tissue distribution. In 1951 a second seminal paper provided more description of lipedema. Fat distribution involves the lower extremities, upper arms, hips, buttocks, thighs, sparing trunks, and feet. Lower extremities are characterized by pain, easy bruisability, firm subcutaneous nodules of adipose tissue, and resistance of fat to traditional diet and exercise.

Background/Aim: The aim of this study was to determine the frequency of fibromyalgia syndrome (FMS) in patients with lipedema and to evaluate the effects of FMS on anxiety, depression, and quality of life (QoL) in this patient group. Methods: Patients with lipedema were invited to participate in a Survey-Monkey questionnaire (according to inclusion and exclusion criteria) that was announced on the facebook page of the lipedema patient community. The demographic and clinical properties, including age, body mass index (BMI), education, marital status, and types and stage of lipedema, were collected. Presence of fibromyalgia was assessed by the questions based on American College of Rheumatology 2016 FMS diagnostic criteria. The Hospital Anxiety and Depression Scale and Short Form-12 (SF-12) were used to assess the anxiety and depression, and QoL respectively. The demographic and clinical characteristics, as well as anxiety/depression level and QoL of lipedema patients were evaluated in regard to the presence (Group 1) and absence (Group 2) of FMS. Results: A total of 354 participants with a mean age of 43.18 ± 9.53 years and BMI of 30.61 ± 6.86 were included. The majority of them were married and had university education. Most of the patients had types 1, 2 and commonly stages 1 and 2 lipedema. One hundred twenty-four patients (35%) satisfied FMS criteria. The demographic characteristics except pain intensity were similar between the groups. The mean anxiety and depression scores of Group 1 were significantly higher compared with Group 2 (13.11 ± 4.2 vs. 9.87 ± 4.65, 10.23 ± 3.79 vs. 8.26 ± 4.15, respectively, p < 0.001). The mental and physical subgroup scores of SF-12 (35.37 ± 8.59 vs. 42.55 ± 10.15, 35.27 ± 8.49 vs. 40.38 ± 11.36, respectively) were significantly lower in Group 1 than in Group 2 (p < 0.001). Conclusion: More than every 3 lipedema patient may have FMS. This comorbidity may increase depression and anxiety, and impair QoL. Therefore, FMS must be kept in mind especially in the assessment of painful lipedema patients to decrease anxiety/depression and enhance the QoL of them.

OBJECTIVE: To evaluate the effects of the venous insufficiency (VI) or lipedema on the symptoms, functions, and quality of life (QoL) of patients with knee osteoarthritis (OA). METHODS: 96 patients with stage 3/4 knee OA were included in the study. Patients were grouped as OA (n = 35), VI + OA (n = 35), and lipedema + OA (n = 26). Range of motion (ROM), Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), short-form (SF-36), and 6-minute walking test (6MWT) were evaluated. RESULTS: WOMAC stiffness score was significantly higher in the VI group than the other groups (p < .05). VAS resting, WOMAC pain, function, and total scores were significantly higher in the lipedema + OA and VI + OA groups than the OA group (p < .05). SF-36-physical role limitation was significantly lower in the lipedema and VI groups (p < .05). CONCLUSION: VI or lipedema accompanying knee OA increases the existing disability due to OA by negatively affecting patients regarding pain, QoL, and physical functioning.

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.

Introdução: O lipedema, recentemente introduzido na 11ª revisão da Classificação Internacional de Doenças. Estima-se que metade das pessoas acometidas pelo lipedema, estejam em sobrepeso ou com obesidade, sendo uma associação de comorbidades que dificulta o diagnóstico. O diagnóstico errôneo é preocupante, pois atrasa o tratamento da doença permitindo a sua progressão. Objetivo: Trata-se de uma revisão integrativa da literatura (RIL) com objetivo de analisar o que se tem construído em pesquisas anteriores relacionadas ao lipedema. Metodologia: A busca dos artigos científicos foram os disponibilizados nos Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Os artigos constassem os Descritores em Ciências da Saúde (DeCS) com as palavras: lipedema and procedimento and cirurgia and mulher, e que fossem revisados por pares, nas línguas inglesa e portuguesa. a partir da aplicação dos critérios previamente definidos O período de busca foi realizado nos meses de maio a agosto de 2023. Resultados e Discussão: Foram elegíveis 12 artigos. A análise dos artigos encontrados possibilitou a evidente necessidade de conhecimento e clareza no diagnóstico do lipedema. As mulheres são as mais afetadas pela doença. A área afetada pode incluir os quadris, as pernas bilateral e simetricamente. E uma das principais características distintivas do lipedema é a preservação dos pés, o que pode criar um degrau distinto no tornozelo. Assim, a importância do diagnóstico diferencial. O procedimento cirúrgico como tratamento apresentou melhores resultados. Entretanto, a associação de todos os tratamentos sobressaiu na qualidade de melhora dos aspectos do lipedema. Conclusão: Essa revisão apontou para o complexo&nbsp; diagnóstico do lipedema.&nbsp; Esse assunto persiste como um desafio e deve instigar mais pesquisadores na busca para um diagnóstico preciso, opções de tratamento e até mesmo no sentido de prevenção para satisfazer a população assistida, no caso a maioria são as mulheres.&nbsp; A melhor opção indicada pelos estudos analisados foi o tratamento cirúrgico realizado pela lipoaspiração.

BACKGROUND: Lipoedema is a symmetrically localised, painful hypertrophy of subcutaneous adipose tissue in the extremities with marked disproportion to the trunk, and almost exclusively affects females. Despite being first described over 80 years ago, the aetiology and pathogenesis of the disease are largely unknown and are currently the subject of intensive research efforts. METHODS: To summarise the current evidence-based literature on the cellular pathologies and aetiology of lipoedema, a PRISMA-based systematic review was conducted within the National Library of Medicine and Cochrane databases. RESULTS: A total of 53 studies were identified and included in this review. The results were classified and summarised into categories. CONCLUSION: Although there has been a significant increase in research activity and recent publication of extensive studies with a histological and molecular genetic focus, the fundamental aetiology and pathology of lipoedema remains largely unclear. The current data shows discrepancies across studies, particularly with regard to the "oedematous" component of lipoedema. The frequently present comorbidities "lymphoedema" and "obesity", primarily in advanced stages of lipoedema, complicate the diagnostic differentiation and clear definition of study cohorts in scientific research.

OBJECTIVE: Lipedema is a debilitating chronic condition predominantly affecting women, characterized by the abnormal accumulation of fat in a symmetrical, bilateral pattern in the extremities, often coinciding with hormonal imbalances. PATIENTS AND METHODS: Despite the conjectured role of sex hormones in its etiology, a definitive link has remained elusive. This study explores the case of a patient possessing a mutation deletion within the C-terminal region of Aldo-keto reductases Member C2 (AKR1C2), Ser320PheTer2, that could lead to heightened enzyme activity. A cohort of 19 additional lipedema patients and 2 additional affected family members14 were enrolled in this study. The two additional affected family members are relatives of the patient with the AKR1C1 L213Q variant, which is included in the 19 cohorts and described in literature. RESULTS: Our investigation revealed that AKR1C2 was overexpressed, as quantified by qPCR, in 5 out of 21 (24%) lipedema patients who did not possess mutations in the AKR1C2 gene. Collectively, these findings implicate AKR1C2 in the pathogenesis of lipedema, substantiating its causative role. CONCLUSIONS: This study demonstrates that the activating mutation in the enzyme or its overexpression is a causative factor in the development of lipedema. Further exploration and replication in diverse populations will bolster our understanding of this significant connection.

BACKGROUND: Lipedema, a complex and enigmatic adipose tissue disorder, remains poorly understood despite its significant impact on the patients' quality of life. Genetic investigations have uncovered potential contributors to its pathogenesis, including somatic mutations, which are nonheritable genetic alterations that can play a pivotal role in the development of this disease. AIM: This review aims to elucidate the role of somatic mutations in the etiology of lipedema by examining their implications in adipose tissue biology, inflammation, and metabolic dysfunction. RESULTS: Studies focusing on leukocyte clones, genetic alterations like TET2 and DNMT3A, and the intricate interplay between adipose tissue and other organs have shed light on the underlying mechanisms driving lipedema. From the study of the scientific literature, mutations to genes correlated to three main pathways could be involved in the somatic development of lipedema: genes related to mitochondrial activity, genes related to localized disorders of subcutaneous adipose tissue, and genes of leukocyte clones. CONCLUSIONS: The insights gained from these diverse studies converge to highlight the complex genetic underpinnings of lipedema and offer potential avenues for therapeutic interventions targeting somatic mutations to alleviate the burden of this condition on affected individuals.

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.