{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:46:59Z","timestamp":1787021219937,"version":"build-2736575974"},"reference-count":29,"publisher":"The Endocrine Society","issue":"4","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Leptin replacement therapy with metreleptin improves metabolic abnormalities in patients with generalized lipodystrophy (GLD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Determine how timing of metreleptin initiation in the clinical course of GLD affects long-term metabolic health.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective analysis of patients \u22656 months old with congenital (n = 47) or acquired (n = 16) GLD treated with metreleptin at the National Institutes of Health since 2001. Least squares means for glycated hemoglobin (HbA1c), insulin area under the curve from oral glucose tolerance tests, triglycerides, urine protein excretion, platelets, transaminases, and aspartate aminotransferase (AST) to Platelet Ratio Index for early and late treatment groups, defined by baseline metabolic health, were analyzed during median 72 (24-108) months\u2019 follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to late groups, early groups based on metabolic status had higher mean \u00b1 SEM insulin area under the curve (20 831 \u00b1 1 vs 11 948 \u00b1 1), lower HbA1c (5.3 \u00b1 0.3 vs 6.8 \u00b1 0.3%), triglycerides (101 \u00b1 1 vs 193 \u00b1 1\u2005mg\/dL), urine protein excretion (85 \u00b1 1.5 vs 404 \u00b1 1.4\u2005mg\/24\u2005h), alanine aminotransferase (30 \u00b1 1 vs 53 \u00b1 1\u2005U\/L), AST (23 \u00b1 1 vs 40 \u00b1 1\u2005U\/L), and AST to Platelet Ratio Index (0.22 \u00b1 1.3 vs 0.78 \u00b1 1.3), and higher platelets (257 \u00b1 24 vs 152 \u00b1 28\u2005K\/\u00b5L) during follow-up (P &amp;lt; .05). Compared to patients \u22656 years old at baseline, patients &amp;lt;6 years had lower HbA1c (4.5 \u00b1 0.5 vs 6.4 \u00b1 0.2%) and higher AST (40 \u00b1 1vs 23 \u00b1 1\u2005U\/L) during follow (P &amp;lt; .05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with GLD who initiated metreleptin before the onset of severe metabolic complications had better long-term control of diabetes, proteinuria, and hypertriglyceridemia. Early treatment may also result is less severe progression of liver fibrosis, but further histological studies are needed to determine the effects of metreleptin therapy on liver disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgae335","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T16:32:36Z","timestamp":1715877156000},"page":"e1051-e1061","source":"Crossref","is-referenced-by-count":11,"title":["Effects of Metreleptin in Patients With Generalized Lipodystrophy Before vs After the Onset of Severe Metabolic Disease"],"prefix":"10.1210","volume":"110","author":[{"given":"Maiah","family":"Brush","sequence":"first","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungyoung","family":"Auh","sequence":"additional","affiliation":[{"name":"National 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