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Background: Lipedema is a chronic disease of subcutaneous adipose tissue that predominantly affects women and is frequently associated with endocrinopathies such as insulin resistance and obesity. Its pathogenesis is still unclear, and treatment, which requires a multi-disciplinary approach, is prolonged over time and is not always effective. There is currently no drug treatment available for this disease. Methods: Five different cases of women with lipedema and insulin resistance, treated with Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) and once-weekly exenatide, in association or not with lifestyle changes (diet or physical activity) for 3 to 6 months are described. Changes in anthropometric parameters, symptoms, clinical findings and the thickness of superficial adipose tissue measured by ultrasound were evaluated. Results: Treatment with exenatide, whether combined with a change in diet or physical activity, resulted in a reduction in the characteristic symptoms of lipedema, in pain evoked by pinching the adipose tissue fold and in the thickness of subcutaneous adipose tissue at the levels of the lower limbs, abdomen and upper limbs. In four out of five cases, a reduction in body weight was observed, particularly during the first three months of treatment and in cases with greater metabolic impairment. Clinical, instrumental and subjective improvements were also observed in cases where there was no reduction in body weight and in patients who had previously undergone lower limb liposuction. Conclusions: The improvement in symptoms and clinical signs of lipedema, in addition to the reduction in adipose tissue in patients with lipedema and insulin resistance with exenatide, suggests a novel pharmacological approach to the disease, which can be combined with other conservative and surgical treatments to promote weight reduction. These results also highlight the association of this disease with metabolic alterations and the fundamental role of an accurate diagnosis followed by the treatment of comorbidities and excess weight in these patients.

Lipoedema is a disease that affects women and is characterised by an abnormal accumulation of fatty tissue, with pain and a feeling of heaviness in the lower limbs. Approximately 30 % of patients also have involvement of the upper limbs. The cause of lipoedema is unknown, but familial clustering of the condition suggests an underlying genetic cause. Oestrogen and hormonal changes appear to be involved, as the condition occurs predominantly in women and is linked to hormonal fluctuations. In Norway, women with lipoedema have had limited access to treatment within the public health service, and the condition is relatively unknown among Norwegian healthcare personnel. Internationally, the diagnosis and treatment of lipoedema are largely based on consensus, as there is a lack of definitive scientific evidence in relation to pathophysiology and treatment. This clinical review presents lipoedema diagnostics and treatment based on clinical experience and international published consensus statements.

Lipedema is a chronic, estrogen-sensitive adipose tissue disorder characterized by disproportionate subcutaneous fat accumulation, fibrosis, inflammation, and resistance to fat mobilization. Despite its high prevalence, lipedema remains poorly understood and frequently misdiagnosed. This narrative review proposes a novel pathophysiological model in which menopause acts as a critical turning point in the progression of lipedema, driven by estrogen receptor imbalance (ERβ predominance over ERα), intracrine estrogen excess, and adipose tissue dysfunction. We demonstrate how menopauseinduced estrogen deficiency amplifies adipose tissue dysfunction by suppressing ERα signaling, enhancing ERβ activity, and disrupting mitochondrial function, insulin sensitivity, and lipid oxidation. Concurrently, the upregulation of aromatase and 17β-HSD1, combined with the suppression of 17β-HSD2, sustains localized estradiol excess, perpetuating inflammation, fibrosis, and immune dysregulation. The molecular signature observed in lipedema closely mirrors that of other estrogen-driven gynecological disorders, such as endometriosis, adenomyosis, and uterine fibroids. Understanding these molecular mechanisms highlights the pivotal role of menopause as a catalyst for disease progression and provides a rationale for targeted therapeutic strategies, including hormonal modulation and metabolic interventions. This review reframes lipedema as an estrogen receptor– driven gynecological disorder, offering a new perspective to improve clinical recognition, diagnosis, and management of this neglected condition.

Lipedema, a chronic and progressive adipose tissue disorder, is characterized by disproportionate fat accumulation, primarily in the lower extremities, often leading to pain, bruising, and mobility impairment. Despite its significant prevalence and impact on quality of life, diagnosis remains challenging, frequently relying on clinical examination and patient history. Ultrasonography holds promise as a non-invasive diagnostic tool, offering insights into subcutaneous tissue characteristics. However, developing a standardized qualitative ultrasonographic classification for lipedema presents considerable challenges due to the heterogeneous nature of fat tissue, variability in disease presentation, and the subjective interpretation inherent in qualitative assessments. This article reviews the current diagnostic landscape of lipedema, explores the potential and limitations of ultrasonography, and critically examines the complexities involved in establishing a robust qualitative ultrasonographic classification. By outlining these challenges, we aim to guide future research towards more objective and standardized imaging criteria, ultimately improving the accuracy and consistency of lipedema diagnosis.

This study investigates long-term volume reduction after microsurgical autologous lymphatic vessel transplantation (LVT) in patients with chronic lymphoedema. Lymphoedema is caused by inadequate lymphatic drainage and leads to swelling, pain, and a reduced quality of life. Conservative treatments often show only limited success, which is why surgical procedures such as LVT are increasingly gaining in importance. In a retrospective long-term analysis, patients who underwent LVT between 1988 and 2010 were examined on average 21.7 years after surgery. The examination included pre- and post-operative volume measurements, which were supplemented by modern 3D body scanner analyses and lymphoscintigraphy. The results show a significant volume reduction both in the short term (p < 0.01) and at the follow-up examination (p = 0.04). There was no significant difference between manual volumetry with circumferential measurements and 3D volumetry (p = 0.775). The improvement in lymph transport capacity was considerable (p = 0.078). This study provides valuable insights for the further development of lymphatic surgery. While preferred surgical methods change over time, this study demonstrates that LVT can make a decisive contribution to improving the quality of life of lymphedema patients.

Background/Objectives: Gender bias in healthcare remains a persistent challenge, partly due to gaps in gender-related knowledge among professionals. While existing instruments assess gender sensitivity and gender-role ideology, there is a lack of generalizable tools specifically designed to evaluate gender-related health knowledge. This study aimed to develop and validate the Gender Knowledge Scale in a sample of 591 nursing students from the University of the Basque Country (Spain). Methods: The 10-item multiple-choice instrument was created using the Nominal Group Technique with a multidisciplinary panel of experts. Results: Psychometric analyses supported a unidimensional structure with acceptable fit indices (CFI = 0.928, RMSEA = 0.025), and items displayed a diverse range of difficulty levels. Knowledge scores were moderately correlated with gender sensitivity but not with gender-role ideology, suggesting that knowledge may influence attitudes but is insufficient to challenge entrenched stereotypes. Knowledge differences emerged across academic years, though not by gender. Misconceptions, particularly regarding menstruation, cardiovascular risk, and pain, were prevalent. Conclusions: The Gender Knowledge Scale is a practical and psychometrically sound tool for assessing gender-related health knowledge among nursing students. While further validation is needed in other populations, the scale may support educational interventions aimed at reducing gender bias in clinical care.

Adipose tissue, or “fat”, has become synonymous with obesity. The public discourse frames a desire to reduce or even banish this tissue at almost every turn, with reasons ranging from aesthetics to health improvements. During decades of research into the development of adipose tissue-reducing interventions, there has also been an increasing acknowledgement and understanding of the physiological necessity for adipose tissue. Functional adipose tissue contributes to overall health due to its role in an incredibly diverse array of processes. For that reason, dysfunction in this tissue continues to be linked to a wide variety of pathologies, from infection to cancer and everything in between. In this book, we gather expert input from those currently expanding this field to provide insight into the importance of adipose tissue.

INTRODUCTION: Lipedema is a chronic and progressive disease that predominantly affects women, characterized by a disproportionate increase in subcutaneous adipose tissue (AT), particularly in the lower limbs. It is associated with significant physical disability, chronic pain, thromboembolism, and psychosocial distress. Despite its profound impact on women's health and quality of life, lipedema remains underrecognized and insufficiently studied, with an estimated prevalence of approximately 10% among women worldwide. Although the exact etiology of lipedema remains unclear, emerging evidence suggests a multifactorial origin involving genetic predisposition, hormonal influences, and vascular dysfunction-all contributing to its development and progression. Current therapeutic options provide only partial symptom relief and remain noncurative, highlighting the urgent need for expanded research and improved management strategies. METHODS: A systematic review was conducted to assess the current understanding of lipedema pathophysiology and current treatment options. Research articles were sourced from PubMed, Web of Science, ScienceDirect, and Scopus databases. Over 100 studies were incorporated. RESULTS: This review provides a comprehensive overview of lipedema, encompassing its clinical features, pathophysiological mechanisms, diagnostic challenges, and current treatment modalities. Additionally, the review discusses whether the molecular and metabolic differences between abdominal and femoral AT depots mirror those observed in classical obesity. CONCLUSIONS: Multidisciplinary, research-informed care is essential for managing lipedema, combining conservative therapies, tailored exercise, and liposuction for advanced cases. More research to better understand the underlying pathophysiology is critical to developing targeted treatments, improving diagnostic accuracy, and informing standardized, evidence-based care.

Lipedema is an abnormal accumulation of adipose tissue, predominantly observed in women, characterised by symmetrical fat deposition and tactile sensitivity in the extremities, affecting both sides of the body. This condition can lead to significant pain, impairing daily activities and causing substantial discomfort.

Background: Postoperative fibrosis is a common and significant complication following liposuction for lipedema, often leading to tissue induration, pain, and compromised aesthetic results. This fibrosis can jeopardize the overall success of the procedure by reducing skin elasticity and altering the intended body contour.Objective: This study aims to evaluate the efficacy of early shockwave therapy (SWT) initiated 1 week after surgery to reduce postoperative fibrosis and preserve the functional and aesthetic outcomes of liposuction in lipedema patients. Methods: A prospective study was conducted on 50 female patients with stage II–III lipedema who underwent power-assisted liposuction (PAL). Patients received SWT sessions three times per week for 3 weeks, starting 7 days postoperatively. Outcomes were compared to a control group of 25 patients who did not receive SWT. Primary endpoints included fibrosis severity assessed by ultrasound elastography, skin elasticity measurements, and patient-reported outcomes on pain and satisfaction. The SWT group exhibited a significant reduction in fibrosis (2.1 ± 0.3 vs 3.8 ± 0.5, p < .001), improved skin elasticity (1.5 ± 0.2 mm vs 1.0 ± 0.3 mm, p < .01), and lower pain scores (2.3 ± 0.8 vs 4.7 ± 1.2, p < .001) compared to the control group. Results: Patient satisfaction was also higher in the SWT group (92% vs 68%, p < .01). Conclusion: Early postoperative shockwave therapy is an effective and safe treatment to reduce fibrosis after liposuction for lipedema. By modulating fibroblast activity, reducing pro-inflammatory cytokines, and improving tissue perfusion, SWT preserves the surgical outcomes and enhances patient satisfaction. These findings suggest that integrating SWT into postoperative protocols could be a valuable strategy to optimize liposuction results in lipedema patients.

Objectives: This study aimed to examine the effects of a multimodal exercise program on edema, pain, exercise capacity, lower extremity muscle strength, and function in patients with lipedema.Methods: The patients diagnosed with lipedema were randomly assigned to either the exercise (n: 11) or control (n: 11) groups. The exercise group participated in supervised group exercises focusing on aerobic and strengthening, twice a week for 6 weeks. The control group received training on physical activity additionally lipedema management. Sociodemographic and clinical characteristics were recorded. Edema (circumference measurements and local tissue water-LTW%), pain intensity (Visual Analogue Scale-VAS) and pressure pain threshold (Algometer), functional exercise capacity (Six minute walk test-6MWT), lower extremity muscle strength (Handheld dynamometer), lower extremity muscle strength/endurance (Sit-to-stand test) and lower extremity function (Lower Extremity Functional Scale-LEFS) were evaluated.Results: In the exercise group, significant reductions in pain during rest, activity, and nighttime, 6MWT distance, quadriceps and hip muscle strength, lower extremity strength/endurance, and function were observed (p < .05). When comparing the groups, no significant differences were found (p > .05); however, clinically, there were differences in limb volumes, pain reduction, muscle strength, and functional improvements, with medium to large effect sizes.Conclusion: The main findings of this study highlight the benefits of structured multimodal exercises for patients with lipedema to improve pain, limb volumes, exercise capacity, lower extremity muscle strength, endurance, and functionality.Clinical trials number: NCT06811961.

Aims Lipedema is a condition often mistaken for other causes of limb swelling including lymphedema and obesity. Lipedema may have a unique metabolic profile. Interrogation of the metabolome is a strategy that could reveal unique biomarkers to distinguish lipedema from lymphedema and obesity. Methods Unbiased metabolomics was utilized to examine 38 BMI-matched overweight patients compared with patients with lipedema, lymphedema, and lipolymphedema. Machine learning identified biomarkers to distinguish diseases, and further examined in a validation cohort of 198 patients with each disorders. Adjustments were made for baseline clinical and demographic variables. Results Plasma metabolomics firstly revealed uric acid as a biomarker that performs well to distinguish between phenotypically similar diseases in patients with elevated BMI. In a validation cohort of 64 patients with lipedema, uric acid (5.05 mg/dL) was compared with 64 patients with lymphedema (5.4 mg/dl), and 70 overweight patients without these conditions (4.6 mg/dL, p<0.05). Uric acid-to-cystatin c ratio distinguished between all three groups (Lipedema: 5.2; Lymphedema: 6.3; overweight: 4.0, p<0.01); however, significance was lost after adjustment for renal function. Conclusion Metabolomic analysis revealed uric acid may differentiate between lipedema, lymphedema, lipolymphedema and obese individuals without those conditions. In a validation cohort, while uric acid was higher in lipedema and lymphedema, uric acid adjusted by cystatin c clearance revealed uric acid to be a less useful marker to distinguish lipedema from lymphedema in the context of renal insufficiency.

Lipedema is a chronic disease in adipose tissue affecting women. The distinctive body appearance in lipedema, often mistaken for obesity, may be detrimental to social life. In our online cross-sectional survey study, conducted from June to September 2021 among 245 women with lipedema, we found significantly more health-related stigma compared to an aged-matched general female population (N = 1872), leading to an overall lower quality of life. Conversely, strong social support was associated with better social and emotional functioning. As such, healthcare professionals must, even in the early stages, recognize this disease and address its impact on psychosocial health and well-being.

There are many different causes of leg and foot swelling, some are benign and transient, others can be debilitating and progressive. Correct diagnosis and early treatment are crucial as conservative measures are most effective before the condition is allowed to progress. Current waiting times in the UK National Health Service (NHS) for General Practitioners and Specialists are leading to delays in care for people with chronic leg swelling. Delayed or inadequate treatment for these patients can lead to irreversible tissue damage, episodes of cellulitis and ulceration. There is a significant impact on quality of life associated with living with the pain, anxiety, and reduced mobility resulting in social isolation. The causes of acute and chronic leg and foot swelling are outlined. Diagnosis and treatment of the common causes of leg and foot swelling in the Western adult population are discussed. The mainstay of treatment for most of these conditions relies on physical therapy and graduated elastic compression garments or inelastic Velcro compression wraps as many do not have a cure.

Lipedema is a painful disease of subcutaneous adipose tissue (SAT) in women. This study determined whether an advanced pneumatic compression device (APCD) improved lipedema SAT depth, swelling, and pain. Women with lipedema started 20–30 mm Hg compression leggings then were randomized to an APCD (Lympha Press Optimal Plus) group for 30 days (treatment; n = 22) or a no APCD (Control; n = 24) group. APCD treatment significantly reduced left leg volume (3D imaging, LymphaTech; p < 0.043) and fluid in the left (p = 0.0018) and right legs (p = 0.0476; SOZO, bioimpedance spectroscopy); controls showed no change. Treatment significantly decreased extracellular fluid (ECF) and intracellular fluid (ICF) in left (p = 0.0077; p = 0.0060) and right legs (p = 0.0476; p ≤ 0.025), respectively. Only ECF decreased significantly in the left (p < 0.0183) and right legs (p = 0.0009) in controls. SAT depth decreased significantly by ultrasound after treatment at the anterior (p ≤ 0.0234) and medial thigh (p ≤ 0.0052), medial knee (p ≤ 0.0002) and posterior calf (p ≤ 0.0118) but not in controls. All signs and symptoms of lipedema improved in the treatment group including swelling (p = 0.0005) and tenderness (pain) of right (p = 0.0003) and left legs (p < 0.0001); only swelling improved in controls (p = 0.0377). In total, 87.5% of RAND SF-36 quality of life improved after treatment (p ≤ 0.0351) compared to 37.5% in controls (p ≤ 0.0475). APCDs are effective treatment for lipedema.

Lipedema is an adipose tissue disorder that principally affects women and is frequently misidentified as obesity or lymphedema. There have been relatively few studies that have precisely defined the pathogenesis, epidemiology, and treatment approaches for lipedema. However, successfully recognizing lipedema as a distinct condition is important for proper management. This review aimed to examine the existing literature on the epidemiology, pathogenesis, clinical presentation, differential diagnosis, and treatments for lipedema. The current research indicates that lipedema appears to be a clinical entity related to genetic factors and fat distribution, although distinct from lymphedema and obesity. Some available treatments include complex decongestive physiotherapy, liposuction, and laser-assisted lipolysis. The management of lipedema is complex and differs from that of lymphedema. Further high-quality randomized controlled trials are urgently needed to continue advancing our understanding of this often neglected disease and exploring optimal medical and surgical treatment regimens tailored specifically for lipedema patients. In summary, despite frequent misdiagnosis, enhanced recognition, and research into customized therapeutic strategies for this poorly characterized but likely underdiagnosed disorder represent promising steps forward. Level of evidence  N/A.

Lipodystrophy presents clinical management challenges due to its varied expression and low incidence. Despite the clinical importance, there has been no systematic evaluation of the research output in terms of geographical distribution, institutional contributions, or emerging trends. This study aims to fill that gap by conducting a comprehensive bibliometric analysis of the global research landscape on lipodystrophy.

Obesity can impair cardiometabolism, but low-carbohydrate diets (LCDs) may be beneficial for mitigating risk. We aimed to investigate the effects of LCDs versus low-fat diets (LFDs), under hypocaloric conditions, on flow-mediated dilation (FMD) in individuals with overweight/obesity. Secondarily, we assessed other cardiovascular markers (systolic blood pressure, diastolic blood pressure, C-reactive protein [CRP], high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides [TG], total cholesterol [TC]), and anthropometric and body composition measurements. PubMed, Scopus, and Web of Science were searched through May 2023 for studies involving hypocaloric LCDs versus LFDs on FMD. Meta-analyses were conducted for LCDs vs. LFDs to calculate weighted mean differences (WMD), including 10 studies reporting FMD (n = 475). Overall, hypocaloric LCDs resulted in a non-significant decrease in FMD compared with hypocaloric LFDs [WMD = −1.04% (95% CI −2.28 to 0.20), p = 0.10], while very-low-carbohydrate diets (VLCDs) significantly reduced FMD when compared with LFDs [WMD = −2.12% (95% CI: −3.35 to −0.9) p = 0.001]. LCDs did not change anthropometric and body composition measurements, nor CRP, blood pressure, HDL, or TC when compared with LFDs. However, LCDs significantly decreased TG [WMD = −19.94 mg/dL (95% CI −31.83 to −8.06), p = 0.001] and increased LDL [WMD = 20.00 mg/dL (95% CI 14.09 to 25.90), p = 0.001] when compared with LFDs. In conclusion, LCDs did not exert superior effects on cardiovascular markers or body composition when compared with LFDs in individuals with overweight or obesity, but LCDs reduced TG and increased LDL levels more than LFDs. Yet, vascular function (FMD) was reduced primarily for VLCDs.

Background: Pain is a prevalent symptom in patients with lipedema predominantly impacting the lower extremities. This study aimed to evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] and vitamin B12 levels and neuropathic pain (NP) in patients diagnosed with lipedema. Methods and Results: A total of 243 patients with lipedema who had 25(OH)D and B12 levels measured in the past 6 months were included in this study. Participants were divided into two groups: Group 1 (N = 78) with NP scores ≥13 and Group 2 (N = 165) with NP scores <13. The Turkish version of the painDETECT questionnaire was used to assess the patients' NP symptoms. Pain levels were measured using the Visual Analog Scale (VAS) and pain threshold through algometric measurement. Group 1 had significantly higher palpation and spontaneous VAS scores, and pain threshold through algometric measurements than Group 2 (p < 0.05). No statistically significant difference was found between the groups regarding vitamin D levels being below 30 ng/mL or vitamin B12 levels being below 400 pg/mL (p > 0.05). Conclusions: No association was found between NP and 25(OH)D or B12 levels in patients with lipedema.