Alexandra B Kinzer1, Robert D Shamburek2, Marissa Lightbourne3, Ranganath Muniyappa1, Rebecca J Brown1. 1. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland. 2. National Heart, Lung, and Blood Institute, Bethesda, Maryland. 3. Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Abstract
CONTEXT: Patients with lipodystrophy have dyslipidemia and insulin resistance. Leptin treatment with metreleptin in lipodystrophy decreases insulin resistance and lowers triglycerides without changing high-density lipoprotein. Detailed measurement of lipoprotein particles with nuclear magnetic resonance (NMR) spectroscopy can offer insights into cardiovascular disease (CVD) risk and lipid metabolism beyond a standard lipid panel. We hypothesized that patients with lipodystrophy would have a more atherogenic lipid profile than controls at baseline, which would be ameliorated with metreleptin treatment. OBJECTIVE: To characterize the lipoprotein profile in patients with lipodystrophy compared with controls and to evaluate effects of metreleptin treatment. DESIGN SETTING PATIENTS AND INTERVENTION: Patients with lipodystrophy (N = 17) were studied before and after metreleptin for 2 weeks and 6 months and compared with 51 insulin-sensitive sex-matched controls. MAIN OUTCOME MEASURES: Lipoprotein profiles were measured by NMR with the LP4 deconvolution algorithm, which reports triglyceride-rich lipoprotein particles (TRLPs), high-density lipoprotein particles (HDLPs), and low-density lipoprotein particles (LDLPs). RESULTS: Patients with lipodystrophy had elevated large TRLPs and smaller HDLPs and LDLPs compared with controls. Five patients with lipodystrophy had chylomicrons, compared with zero controls. Metreleptin decreased the size and concentration of TRLPs, eliminated chylomicrons in all but one patient, decreased LDLPs, and increased LDLP size. Metreleptin treatment did not have major effects on HDLPs. CONCLUSIONS: Patients with lipodystrophy had an atherogenic lipoprotein profile at baseline consistent with elevated CVD risk, which improved after metreleptin treatment. The presence of fasting chylomicrons in a subset of patients with lipodystrophy suggests saturation of chylomicron clearance by lipoprotein lipase. Published by Oxford University Press on behalf of the Endocrine Society 2019.
CONTEXT: Patients with lipodystrophy have dyslipidemia and insulin resistance. Leptin treatment with metreleptin in lipodystrophy decreases insulin resistance and lowers triglycerides without changing high-density lipoprotein. Detailed measurement of lipoprotein particles with nuclear magnetic resonance (NMR) spectroscopy can offer insights into cardiovascular disease (CVD) risk and lipid metabolism beyond a standard lipid panel. We hypothesized that patients with lipodystrophy would have a more atherogenic lipid profile than controls at baseline, which would be ameliorated with metreleptin treatment. OBJECTIVE: To characterize the lipoprotein profile in patients with lipodystrophy compared with controls and to evaluate effects of metreleptin treatment. DESIGN SETTING PATIENTS AND INTERVENTION: Patients with lipodystrophy (N = 17) were studied before and after metreleptin for 2 weeks and 6 months and compared with 51 insulin-sensitive sex-matched controls. MAIN OUTCOME MEASURES: Lipoprotein profiles were measured by NMR with the LP4 deconvolution algorithm, which reports triglyceride-rich lipoprotein particles (TRLPs), high-density lipoprotein particles (HDLPs), and low-density lipoprotein particles (LDLPs). RESULTS: Patients with lipodystrophy had elevated large TRLPs and smaller HDLPs and LDLPs compared with controls. Five patients with lipodystrophy had chylomicrons, compared with zero controls. Metreleptin decreased the size and concentration of TRLPs, eliminated chylomicrons in all but one patient, decreased LDLPs, and increased LDLP size. Metreleptin treatment did not have major effects on HDLPs. CONCLUSIONS: Patients with lipodystrophy had an atherogenic lipoprotein profile at baseline consistent with elevated CVD risk, which improved after metreleptin treatment. The presence of fasting chylomicrons in a subset of patients with lipodystrophy suggests saturation of chylomicron clearance by lipoprotein lipase. Published by Oxford University Press on behalf of the Endocrine Society 2019.
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