Joseph Jalaja, Shamburek Robert D, Cochran Elaine K, Gorden Phillip, Brown Rebecca J
Diabetes, Endocrinology, and Obesity Branch (J.J., E.K.C., P.G., R.J.B.), National Institute of Diabetes and Digestive and Kidney Diseases, and National Heart Lung and Blood Institute (R.D.S.), National Institutes of Health, Bethesda, Maryland 20892.
J Clin Endocrinol Metab. 2014 Sep;99(9):E1676-80. doi: 10.1210/jc.2014-1878. Epub 2014 Jun 13.
There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%).
Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome.
DESIGN, SETTING, AND PATIENTS: This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy.
Metreleptin (0.06-0.24 mg/kg/d) was administered for 24 months in lipodystrophy.
Serum triglycerides and HDL-C were measured.
At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = -0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C.
The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition.
在胰岛素抵抗中，甘油三酯与高密度脂蛋白胆固醇（HDL-C）呈负相关，即胰岛素抵抗的改善会降低甘油三酯并升高HDL-C。脂肪营养不良患者存在极端的胰岛素抵抗，伴有高甘油三酯和低HDL-C。脂肪营养不良患者补充瘦素会使甘油三酯显著降低（约60%）。
我们的目的是研究米替普明对脂肪营养不良患者甘油三酯和HDL-C的影响，并与肥胖相关代谢综合征干预措施中甘油三酯和HDL-C的变化进行对比。
设计、地点和患者：这项在美国国立卫生研究院进行的开放标签非随机研究纳入了82例各种形式脂肪营养不良的患者。
对脂肪营养不良患者给予米替普明（0.06 - 0.24 mg/kg/天）治疗24个月。
测量血清甘油三酯和HDL-C。
在基线时，脂肪营养不良患者的HDL-C较低（30±1 mg/dL），甘油三酯较高（961±220 mg/dL），两者呈负相关（R = -0.37，P = 0.0006）。尽管甘油三酯有显著改善，但米替普明治疗后HDL-C没有变化，且甘油三酯的个体变化对HDL-C变化的预测作用较弱。在线性回归分析中，在肥胖患者中，log（甘油三酯）每降低0.1 mg/dL与HDL-C升高4.2 mg/dL相关；而在脂肪营养不良患者中，log（甘油三酯）每降低0.1 mg/dL仅与HDL-C升高0.6 mg/dL相关。
肥胖相关代谢综合征干预措施中所见的甘油三酯与HDL-C变化之间的正常相互关系，在数量上与脂肪营养不良患者对米替普明治疗的反应不同。需要进一步开展工作以了解这种情况下HDL-C的调节机制。
