Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
J Clin Endocrinol Metab. 2019 Aug 1;104(8):3068-3076. doi: 10.1210/jc.2018-02787.
Familial partial lipodystrophy (FPLD) is most commonly caused by pathogenic variants in LMNA and PPARG. Leptin replacement with metreleptin has largely been studied in the LMNA group.
To understand the efficacy of metreleptin in PPARG vs LMNA pathogenic variants and investigate predictors of metreleptin responsiveness.
Subgroup analysis of a prospective open-label study of metreleptin in lipodystrophy.
National Institutes of Health, Bethesda, Maryland.
Patients with LMNA (n = 22) or PPARG pathogenic variants (n = 7), leptin <12 ng/mL, and diabetes, insulin resistance, or high triglycerides.
Metreleptin (0.08 to 0.16 mg/kg) for 12 months.
Hemoglobin A1c (HbA1c), lipids, and medication use at baseline and after 12 months.
Baseline characteristics were comparable in patients with PPARG and LMNA: HbA1c, 9.2 ± 2.3 vs 7.8 ± 2.1%; median [25th, 75th percentile] triglycerides, 1377 [278, 5577] vs 332 [198, 562] mg/dL; leptin, 6.3 ± 3.8 vs 5.5 ± 2.5 ng/mL (P > 0.05). After 12 months of metreleptin, HbA1c declined to 7.7 ± 2.4 in PPARG and 7.3 ± 1.7% in LMNA; insulin requirement decreased from 3.8 [2.7, 4.3] to 2.1 [1.6, 3.0] U/kg/d in PPARG and from 1.7 [1.3, 4.4] to 1.2 [1.0, 2.3] U/kg/d in LMNA (P < 0.05). Triglycerides decreased to 293 [148, 406] mg/dL in LMNA (P < 0.05), but changes were not significant in PPARG: 680 [296, 783] mg/dL at 12 months (P = 0.2). Both groups were more likely to experience clinically relevant triglyceride (≥30%) or HbA1c (≥1%) reduction with metreleptin if they had baseline triglycerides ≥500 mg/dL or HbA1c >8%.
Metreleptin resulted in similar metabolic improvements in patients with LMNA and PPARG pathogenic variants. Our findings support the efficacy of metreleptin in patients with the two most common genetic causes of FPLD.
家族性部分脂肪营养不良（FPLD）最常见的病因是 LMNA 和 PPARG 的致病性变异。米格列醇治疗肥胖症的研究主要集中在 LMNA 组。
了解米格列醇在 PPARG 与 LMNA 致病性变异中的疗效，并探讨米格列醇反应性的预测因素。
米格列醇治疗脂肪营养不良的前瞻性开放标签研究的亚组分析。
美国马里兰州贝塞斯达国立卫生研究院。
患有 LMNA（n=22）或 PPARG 致病性变异（n=7）、瘦素<12ng/mL 且患有糖尿病、胰岛素抵抗或高甘油三酯血症的患者。
米格列醇（0.08 至 0.16mg/kg）治疗 12 个月。
基线和 12 个月时的血红蛋白 A1c（HbA1c）、血脂和药物使用情况。
PPARG 和 LMNA 患者的基线特征相似：HbA1c，9.2±2.3 vs 7.8±2.1%；中位数[25 分位，75 分位]甘油三酯，1377[278，5577] vs 332[198，562]mg/dL；瘦素，6.3±3.8 vs 5.5±2.5ng/mL（P>0.05）。米格列醇治疗 12 个月后，PPARG 患者的 HbA1c 降至 7.7±2.4%，LMNA 患者降至 7.3±1.7%；胰岛素需求量从 3.8[2.7，4.3]U/kg/d 降至 2.1[1.6，3.0]U/kg/d（PPARG，P<0.05），从 1.7[1.3，4.4]U/kg/d 降至 1.2[1.0，2.3]U/kg/d（LMNA，P<0.05）。LMNA 患者的甘油三酯降至 293[148，406]mg/dL（P<0.05），但 PPARG 患者的变化不显著：680[296，783]mg/dL（P=0.2）。如果基线甘油三酯≥500mg/dL 或 HbA1c>8%，两组患者更有可能出现临床相关的甘油三酯（≥30%）或 HbA1c（≥1%）降低。
米格列醇在 LMNA 和 PPARG 致病性变异患者中均能改善代谢。我们的研究结果支持米格列醇在 FPLD 最常见的两种遗传病因患者中的疗效。
