{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:59:01Z","timestamp":1777618741688,"version":"3.51.4"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Familial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma (<jats:italic>PPARG<\/jats:italic>) gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>We present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARG<jats:sub>Glu157Gly<\/jats:sub> variant. After six months of metreleptin treatment, HbA1c decreased from 10 to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg\/dl to 198 mg\/dl.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as difficult-to-classify and manages diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.684182","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T06:36:55Z","timestamp":1623134215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance"],"prefix":"10.3389","volume":"12","author":[{"given":"Vaia","family":"Lambadiari","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aikaterini","family":"Kountouri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eirini","family":"Maratou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavros","family":"Liatis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George D.","family":"Dimitriadis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrik","family":"Karpe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2018.11.004","article-title":"Lipodystrophies, Dyslipidaemias and Atherosclerotic Cardiovascular Disease","volume":"51","author":"Hussain","year":"2019","journal-title":"Pathology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2017.04.010","article-title":"Clinical Presentations, Metabolic Abnormalities and End-Organ Complications in Patients With Familial Partial Lipodystrophy","volume":"72","author":"Akinci","year":"2017","journal-title":"Metabolism"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-02730","article-title":"Comorbidities and Survival in Patients With Lipodystrophy: An International Chart Review Study","volume":"104","author":"Akinci","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.20111159","article-title":"Clinical Review#: Lipodystrophies: Genetic and Acquired Body Fat Disorders","volume":"96","author":"Garg","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra025261","article-title":"Acquired and Inherited Lipodystrophies","volume":"350","author":"Garg","year":"2004","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/47254","article-title":"Dominant Negative Mutations in Human PPARgamma Associated With Severe Insulin Resistance, Diabetes Mellitus and Hypertension","volume":"402","author":"Barroso","year":"1999","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.1.8290","article-title":"A Novel Heterozygous Mutation in Peroxisome Proliferator-Activated Receptor-Gamma Gene in a Patient With Familial Partial Lipodystrophy","volume":"87","author":"Agarwal","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2356","article-title":"Fatty Acid Metabolism in Patients With PPARgamma Mutations","volume":"93","author":"Tan","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/nu7115475","article-title":"The Subtle Balance Between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis","volume":"7","author":"Saponaro","year":"2015","journal-title":"Nutrients"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.123","article-title":"Congenital Generalized Lipodystrophies\u2013New Insights Into Metabolic Dysfunction","volume":"11","author":"Patni","year":"2015","journal-title":"Nat Rev Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.4.910","article-title":"Human Metabolic Syndrome Resulting From Dominant-Negative Mutations in the Nuclear Receptor Peroxisome Proliferator-ActivatedReceptor-Gamma","volume":"52","author":"Savage","year":"2003","journal-title":"Diabetes"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4158\/endp.19.1.v767575m65p5mr06","article-title":"American Association of Clinical Endocrinologists. 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