{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:00:04Z","timestamp":1790298004389,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Obesity"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lipoedema is a painful adipose tissue disorder marked by disproportionate limb fat and often misclassified as generalized obesity or lymphoedema. This review examines its metabolic phenotype and implications for cardiometabolic assessment and management. PubMed\/MEDLINE was searched from inception through May 2026 for studies on lipoedema, obesity, body composition, metabolic risk, insulin resistance, diabetes, lifestyle interventions, pharmacotherapy and liposuction. Relevant clinical, mechanistic, review and consensus literature was narratively synthesized. Evidence is limited and heterogeneous, consisting mainly of observational cohorts, referral\u2010centre series, mechanistic studies and consensus guidance, predominantly involving women. Some studies report fewer metabolic abnormalities in women with lipoedema than in women with BMI\u2010matched lifestyle\u2010related overweight or obesity. These findings do not establish metabolic protection and may reflect differences in central adiposity, disease stage, diagnostic criteria, body composition, inflammation or referral patterns. Obesity and glucose\u2010lowering therapies, including glucagon\u2010like peptide\u20101 receptor agonists, remain appropriate for established indications, but direct modification of lipoedema has not been demonstrated. Cardiometabolic risk in lipoedema should be assessed using a phenotype\u2010based approach that distinguishes painful limb adiposity from central and ectopic fat while considering age, sex, menopausal status and established risk factors. BMI should be interpreted with waist measures, metabolic screening, body composition and muscle mass when relevant. Prospective studies using standardized diagnostic criteria, direct measures of insulin sensitivity, detailed body composition and clinically meaningful outcomes are needed to clarify long\u2010term risk and distinguish lipoedema biology from coexisting central obesity.<\/jats:p>","DOI":"10.1111\/cob.70115","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:31:41Z","timestamp":1790033501000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipoedema and Obesity Misclassification: A Phenotype Based Approach to Cardiometabolic Risk Beyond Body Mass Index"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6198-4352","authenticated-orcid":false,"given":"Ron T.","family":"Varghese","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Diabetes &amp; Metabolism University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana G.","family":"Varghese","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Diabetes &amp; Metabolism University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2011.153"},{"issue":"22","key":"e_1_2_18_3_1","first-page":"396","article-title":"Lipedema\u2010Pathogenesis, Diagnosis, and Treatment Options","volume":"117","author":"Kruppa P.","year":"2020","journal-title":"Deutsches \u00c4rzteblatt International"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(25)37697-4"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-34-5-1243"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.1515\/hmbci-2017-0076"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33313"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26157074"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-68232-z"},{"key":"e_1_2_18_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192644"},{"key":"e_1_2_18_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8747461"},{"issue":"5","key":"e_1_2_18_12_1","first-page":"994","article-title":"Lipedema and Obesity Are Associated With Distinct Tissue Fluid and Fat MRI Characteristics","volume":"28","author":"Crescenzi R.","year":"2020","journal-title":"Obesity (Silver Spring)"},{"issue":"3","key":"e_1_2_18_13_1","first-page":"561","article-title":"Lipedema: A Disease Triggered by M2 Polarized Macrophages?","volume":"13","author":"Grewal T.","year":"2025","journal-title":"Biomedicine"},{"key":"e_1_2_18_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126621"},{"issue":"3","key":"e_1_2_18_15_1","first-page":"639","article-title":"The Role of Oxidative Stress in the Pathomechanism of Lipedema: Implications for Treatment","volume":"12","author":"Blaszczak R.","year":"2023","journal-title":"Antioxidants"},{"key":"e_1_2_18_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46110710"},{"issue":"10","key":"e_1_2_18_17_1","first-page":"1179","article-title":"Body Mass Index vs Waist\u2010To\u2010Height Ratio in Patients With Lipohyperplasia Dolorosa","volume":"21","author":"Brenner E.","year":"2023","journal-title":"Journal der Deutschen Dermatologischen Gesellschaft"},{"issue":"4","key":"e_1_2_18_18_1","first-page":"867","article-title":"Metabolic Alterations in Women With Lipedema Compared to Women With Lifestyle\u2010Induced Overweight\/Obesity","volume":"13","author":"Jeziorek M.","year":"2025","journal-title":"Biomedicine"},{"key":"e_1_2_18_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031599"},{"issue":"2","key":"e_1_2_18_20_1","first-page":"71","article-title":"Lipedema Is Associated With Increased Aortic Stiffness","volume":"45","author":"Szolnoky G.","year":"2012","journal-title":"Lymphology"},{"key":"e_1_2_18_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/s24051673"},{"key":"e_1_2_18_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2025.108716"},{"key":"e_1_2_18_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.24026"},{"key":"e_1_2_18_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/clinpract15070128"},{"key":"e_1_2_18_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2026.1728651"},{"key":"e_1_2_18_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13953"},{"key":"e_1_2_18_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuaf203"},{"key":"e_1_2_18_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_2_18_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.19897"},{"issue":"3","key":"e_1_2_18_30_1","article-title":"GLP\u20101 Receptor Agonists and Lipedema Adipose Tissue: Pathophysiological Considerations","volume":"25","author":"Al\u2010Ghadban S.","year":"2024","journal-title":"Obesity Reviews"},{"key":"e_1_2_18_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/DSS.0000000000005172"},{"issue":"2","key":"e_1_2_18_32_1","article-title":"Efficacy of Liposuction in the Treatment of Lipedema: A Meta\u2010Analysis","volume":"16","author":"Amato A. 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