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- Title
Lipid regulation in lipodystrophy versus the obesity-associated metabolic syndrome: the dissociation of HDL-C and triglycerides.
- Authors
Joseph, Jalaja; Shamburek, Robert D; Cochran, Elaine K; Gorden, Phillip; Brown, Rebecca J
- Abstract
<bold>Context: </bold>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%).<bold>Objective: </bold>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.<bold>Design, Setting, and Patients: </bold>This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy.<bold>Intervention: </bold>Metreleptin (0.06-0.24 mg/kg/d) was administered for 24 months in lipodystrophy.<bold>Main Outcome Measures: </bold>Serum triglycerides and HDL-C were measured.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2014, Vol 99, Issue 9, pE1676
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2014-1878