{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:35:13Z","timestamp":1772580913705,"version":"3.50.1"},"reference-count":24,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Context: Acquired generalized lipodystrophy (AGL) is marked by severe insulin resistance and hypertriglyceridemia. Rarely, AGL and type 1 diabetes (T1D) coexist.<\/jats:p>\n               <jats:p>Objective: Our objective was to describe the response to leptin therapy in patients with coexisting AGL and T1D and to document the autoimmune diseases associated with AGL.<\/jats:p>\n               <jats:p>Design and Setting: We conducted an open-label prospective study at the Clinical Research Center of the National Institutes of Health.<\/jats:p>\n               <jats:p>Patients: Participants included 50 patients with generalized or partial lipodystrophy (acquired or congenital); two patients had both AGL and T1D.<\/jats:p>\n               <jats:p>Intervention: Patients were treated with 12 months of recombinant human leptin administration to achieve high-normal serum concentrations.<\/jats:p>\n               <jats:p>Results: Two patients had both AGL and T1D. The first was diagnosed with T1D at age 8 yr. Beginning at age 11 yr, he developed generalized lipodystrophy, elevated transaminases, and poor glycemic control [hemoglobin A1c (HbA1c) 10.7%] despite markedly increased insulin requirements (3.3\u20135 U\/kg\u00b7d). Further evaluation revealed hypoleptinemia and hypertriglyceridemia. At age 15 yr, leptin therapy was initiated, and after 1 yr, his insulin requirements fell to 1 U\/kg\u00b7d, his glycemic control improved (HbA1c 8.4%), and both his triglycerides and transaminases normalized. The second patient developed concurrent AGL and T1D at age 6 yr. Despite insulin doses of up to 32 U\/kg\u00b7d, she developed poor glycemic control (HbA1c 10.6%), hypertriglyceridemia (2984 mg\/dl), elevated transaminases, and nonalcoholic steatohepatitis. At age 13 yr, leptin therapy was started, and after 1 yr, her glycemic control improved (HbA1c 7.3%) and her insulin requirements decreased (17 U\/kg\u00b7d). Her triglycerides remained elevated but were improved (441 mg\/dl).<\/jats:p>\n               <jats:p>Conclusions: Long-term recombinant leptin therapy is effective in treating the insulin resistance of patients with the unusual combination of T1D and AGL.<\/jats:p>","DOI":"10.1210\/jc.2007-1856","type":"journal-article","created":{"date-parts":[[2007,10,17]],"date-time":"2007-10-17T03:19:39Z","timestamp":1192591179000},"page":"26-31","source":"Crossref","is-referenced-by-count":59,"title":["Type 1 Diabetes Associated with Acquired Generalized Lipodystrophy and Insulin Resistance: The Effect of Long-Term Leptin Therapy"],"prefix":"10.1210","volume":"93","author":[{"given":"Jean Y.","family":"Park","sequence":"first","affiliation":[{"name":"Clinical Endocrinology Branch (J.Y.P., A.Y.C., E.K.C., P.G.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angeline Y.","family":"Chong","sequence":"additional","affiliation":[{"name":"Clinical Endocrinology Branch (J.Y.P., A.Y.C., E.K.C., P.G.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine K.","family":"Cochran","sequence":"additional","affiliation":[{"name":"Clinical Endocrinology Branch (J.Y.P., A.Y.C., E.K.C., P.G.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David E.","family":"Kleiner","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, and Laboratory of Pathology (D.E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Haller","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology (M.J.H., D.A.S.), Department of Pediatrics, University of Florida, Gainesville, Florida 32610"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desmond A.","family":"Schatz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology (M.J.H., D.A.S.), Department of Pediatrics, University of Florida, Gainesville, Florida 32610"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip","family":"Gorden","sequence":"additional","affiliation":[{"name":"Clinical Endocrinology Branch (J.Y.P., A.Y.C., E.K.C., P.G.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613320574700_R1","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1056\/NEJMra025261","article-title":"Acquired and inherited lipodystrophies.","volume":"350","author":"Garg","year":"2004","journal-title":"N Engl J Med"},{"key":"2020071613320574700_R2","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1210\/jc.2006-1546","article-title":"Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy.","volume":"92","author":"Ebihara","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613320574700_R3","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.2337\/diabetes.54.7.1994","article-title":"Long-term efficacy of leptin replacement in patients with generalized lipodystrophy.","volume":"54","author":"Javor","year":"2005","journal-title":"Diabetes"},{"key":"2020071613320574700_R4","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.metabol.2003.10.019","article-title":"Changes in body composition in patients with severe lipodystrophy after leptin replacement therapy.","volume":"53","author":"Moran","year":"2004","journal-title":"Metabolism"},{"key":"2020071613320574700_R5","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1056\/NEJMoa012437","article-title":"Leptin-replacement therapy for lipodystrophy.","volume":"346","author":"Oral","year":"2002","journal-title":"N Engl J Med"},{"key":"2020071613320574700_R6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/00005792-200303000-00007","article-title":"Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature.","volume":"82","author":"Misra","year":"2003","journal-title":"Medicine"},{"key":"2020071613320574700_R7","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/01.md.0000111061.69212.59","article-title":"Clinical features and metabolic and autoimmune derangements in acquired partial lipodystrophy: report of 35 cases and review of the literature.","volume":"83","author":"Misra","year":"2004","journal-title":"Medicine"},{"key":"2020071613320574700_R8","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1001\/archderm.1987.01660360090018","article-title":"Lipoatrophic panniculitis: a possible autoimmune inflammatory disease of fat. Report of three cases.","volume":"123","author":"Billings","year":"1987","journal-title":"Arch Dermatol"},{"key":"2020071613320574700_R9","first-page":"610","article-title":"Lipodystrophy in patients with juvenile dermatomyositis: evaluation of clinical and metabolic abnormalities.","volume":"28","author":"Huemer","year":"2001","journal-title":"J Rheumatol"},{"key":"2020071613320574700_R10","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.metabol.2006.11.010","article-title":"Long-term efficacy of leptin replacement in patients with Dunnigan-type familial partial lipodystrophy.","volume":"56","author":"Park","year":"2007","journal-title":"Metabolism"},{"key":"2020071613320574700_R11","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1210\/jc.2003-032140","article-title":"Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: baseline characteristics and course during recombinant leptin therapy.","volume":"89","author":"Javor","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613320574700_R12","doi-asserted-by":"crossref","first-page":"34268","DOI":"10.1074\/jbc.M300043200","article-title":"Liver peroxisome proliferator-activated receptor \u03b3 contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass.","volume":"278","author":"Gavrilova","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071613320574700_R13","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1093\/ndt\/12.9.1804","article-title":"Lipodystrophy in MCGN type II: the clue to links between the adipocyte and the complement system.","volume":"12","author":"Mathieson","year":"1997","journal-title":"Nephrol Dial Transplant"},{"key":"2020071613320574700_R14","doi-asserted-by":"crossref","first-page":"263","DOI":"10.7326\/0003-4819-133-4-200008150-00009","article-title":"Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes.","volume":"133","author":"Arioglu","year":"2000","journal-title":"Ann Intern Med"},{"key":"2020071613320574700_R15","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1046\/j.1464-5491.2003.01034.x","article-title":"Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene.","volume":"20","author":"Owen","year":"2003","journal-title":"Diabet Med"},{"key":"2020071613320574700_R16","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1053\/meta.2002.30506","article-title":"Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes.","volume":"51","author":"Hirose","year":"2002","journal-title":"Metabolism"},{"key":"2020071613320574700_R17","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/S0026-0495(99)90122-1","article-title":"Effects of troglitazone on fat distribution in the treatment of male type 2 diabetes.","volume":"48","author":"Kawai","year":"1999","journal-title":"Metabolism"},{"key":"2020071613320574700_R18","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1210\/jcem.87.6.8567","article-title":"Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients.","volume":"87","author":"Miyazaki","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613320574700_R19","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/oby.2002.137","article-title":"Effect of rosiglitazone on insulin sensitivity and body composition in type 2 diabetic patients [corrected].","volume":"10","author":"Carey","year":"2002","journal-title":"Obes Res [Erratum (2002) 10:(11) following table of contents]"},{"key":"2020071613320574700_R20","doi-asserted-by":"crossref","first-page":"908","DOI":"10.2337\/diacare.22.6.908","article-title":"Effect of troglitazone on body fat distribution in type 2 diabetic patients.","volume":"22","author":"Mori","year":"1999","journal-title":"Diabetes Care"},{"key":"2020071613320574700_R21","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.2337\/diacare.23.8.1067","article-title":"Efficacy of troglitazone on body fat distribution in type 2 diabetes.","volume":"23","author":"Akazawa","year":"2000","journal-title":"Diabetes Care"},{"key":"2020071613320574700_R22","doi-asserted-by":"crossref","first-page":"5909","DOI":"10.4049\/jimmunol.166.10.5909","article-title":"Requirement for leptin in the induction and progression of autoimmune encephalomyelitis.","volume":"166","author":"Matarese","year":"2001","journal-title":"J Immunol"},{"key":"2020071613320574700_R23","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1210\/jc.2005-1220","article-title":"Leptin replacement therapy modulates circulating lymphocyte subsets and cytokine responsiveness in severe lipodystrophy.","volume":"91","author":"Oral","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613320574700_R24","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/hep.20672","article-title":"Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy.","volume":"41","author":"Javor","year":"2005","journal-title":"Hepatology"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/1\/26\/9051772\/jcem0026.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/1\/26\/9051772\/jcem0026.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:03:51Z","timestamp":1594944231000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/93\/1\/26\/2598036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,1]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2007-1856","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,1]]}}}