Brush Maiah, Auh Sungyoung, Cochran Elaine, Tuska Rebecca, Koh Christopher, Kleiner David E, Lightbourne Marissa, Brown Rebecca J
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Clin Endocrinol Metab. 2025 Mar 17;110(4):e1051-e1061. doi: 10.1210/clinem/dgae335.
Leptin replacement therapy with metreleptin improves metabolic abnormalities in patients with generalized lipodystrophy (GLD).
Determine how timing of metreleptin initiation in the clinical course of GLD affects long-term metabolic health.
Retrospective analysis of patients ≥6 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' follow-up.
Compared to late groups, early groups based on metabolic status had higher mean ± SEM insulin area under the curve (20 831 ± 1 vs 11 948 ± 1), lower HbA1c (5.3 ± 0.3 vs 6.8 ± 0.3%), triglycerides (101 ± 1 vs 193 ± 1 mg/dL), urine protein excretion (85 ± 1.5 vs 404 ± 1.4 mg/24 h), alanine aminotransferase (30 ± 1 vs 53 ± 1 U/L), AST (23 ± 1 vs 40 ± 1 U/L), and AST to Platelet Ratio Index (0.22 ± 1.3 vs 0.78 ± 1.3), and higher platelets (257 ± 24 vs 152 ± 28 K/µL) during follow-up (P < .05). Compared to patients ≥6 years old at baseline, patients <6 years had lower HbA1c (4.5 ± 0.5 vs 6.4 ± 0.2%) and higher AST (40 ± 1vs 23 ± 1 U/L) during follow (P < .05).
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.
用美曲普明进行瘦素替代疗法可改善泛发性脂肪营养不良（GLD）患者的代谢异常。
确定在GLD临床病程中开始使用美曲普明的时机如何影响长期代谢健康。
对自2001年以来在美国国立卫生研究院接受美曲普明治疗的≥6个月大的先天性（n = 47）或后天性（n = 16）GLD患者进行回顾性分析。根据基线代谢健康状况定义的早期和晚期治疗组，在中位72（24 - 108）个月的随访期间，分析糖化血红蛋白（HbA1c）、口服葡萄糖耐量试验的胰岛素曲线下面积、甘油三酯、尿蛋白排泄、血小板、转氨酶和天冬氨酸转氨酶（AST）与血小板比值指数的最小二乘均值。
与晚期组相比，基于代谢状态的早期组在随访期间的胰岛素曲线下面积均值±标准误更高（20831±1对11948±1），HbA1c更低（5.3±0.3对6.8±0.3%）、甘油三酯更低（101±1对193±1mg/dL）、尿蛋白排泄更低（85±1.5对404±1.4mg/24h）、丙氨酸转氨酶更低（30±1对53±1U/L）、AST更低（23±1对40±1U/L）以及AST与血小板比值指数更低（0.22±1.3对0.78±1.3），血小板更高（257±24对152±28K/µL）（P < 0.05）。与基线时≥6岁的患者相比，<6岁的患者在随访期间HbA1c更低（4.5±0.5对6.4±0.2%）且AST更高（40±1对23±1U/L）（P < 0.05）。
在严重代谢并发症发作前开始使用美曲普明的GLD患者对糖尿病、蛋白尿和高甘油三酯血症有更好长期控制。早期治疗也可能导致肝纤维化进展不那么严重，但需要进一步的组织学研究来确定美曲普明疗法对肝脏疾病的影响。
