Effects of Extended-Release Niacin on the Postprandial Metabolism of Lp(a) and ApoB-100-Containing Lipoproteins in Statin-Treated Men with Type 2 Diabetes Mellitus

Esther Ooi, Gerald Watts, Dick Chan, Jing Pang, V.S. Tenneti, Sandy Hamilton, S.P. Mccormick, S.M. Marcovina, Hugh Barrett

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Abstract

© 2015 American Heart Association, Inc. The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration. Approach and Results-The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL,-49.8%; intermediate-density lipoprotein,-44.7%; LDL,-46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%). Conclusions-In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN.
Original languageEnglish
Pages (from-to)2686-2693
JournalArteriosclerosis, thrombosis, and vascular biology
Volume35
Issue number12
DOIs
Publication statusPublished - Dec 2015

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Apolipoprotein B-100
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipoprotein(a)
Niacin
VLDL Lipoproteins
Type 2 Diabetes Mellitus
Lipoproteins
IDL Lipoproteins
LDL Lipoproteins
Apoprotein(a)
Fats
Postprandial Period
Body Weight Changes
Leucine
Intravenous Administration
LDL Cholesterol
Gas Chromatography-Mass Spectrometry
Cross-Over Studies
Insulin Resistance
Fasting

Cite this

@article{050e8b6739874b6cbc8b15bd11b162a7,
title = "Effects of Extended-Release Niacin on the Postprandial Metabolism of Lp(a) and ApoB-100-Containing Lipoproteins in Statin-Treated Men with Type 2 Diabetes Mellitus",
abstract = "{\circledC} 2015 American Heart Association, Inc. The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration. Approach and Results-The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87{\%} fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5{\%}) and the production rates of apo(a) (-41.5{\%}) and Lp(a)-apoB-100 (-32.1{\%}); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7{\%}), intermediate-density lipoprotein (-33.6{\%}), and LDL (-18.3{\%}) apoB-100 concentrations and the corresponding production rates (VLDL,-49.8{\%}; intermediate-density lipoprotein,-44.7{\%}; LDL,-46.1{\%}). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9{\%}). Conclusions-In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN.",
author = "Esther Ooi and Gerald Watts and Dick Chan and Jing Pang and V.S. Tenneti and Sandy Hamilton and S.P. Mccormick and S.M. Marcovina and Hugh Barrett",
year = "2015",
month = "12",
doi = "10.1161/ATVBAHA.115.306136",
language = "English",
volume = "35",
pages = "2686--2693",
journal = "ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY",
issn = "1079-5642",
publisher = "Lippincott Williams & Wilkins",
number = "12",

}

TY - JOUR

T1 - Effects of Extended-Release Niacin on the Postprandial Metabolism of Lp(a) and ApoB-100-Containing Lipoproteins in Statin-Treated Men with Type 2 Diabetes Mellitus

AU - Ooi, Esther

AU - Watts, Gerald

AU - Chan, Dick

AU - Pang, Jing

AU - Tenneti, V.S.

AU - Hamilton, Sandy

AU - Mccormick, S.P.

AU - Marcovina, S.M.

AU - Barrett, Hugh

PY - 2015/12

Y1 - 2015/12

N2 - © 2015 American Heart Association, Inc. The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration. Approach and Results-The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL,-49.8%; intermediate-density lipoprotein,-44.7%; LDL,-46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%). Conclusions-In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN.

AB - © 2015 American Heart Association, Inc. The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration. Approach and Results-The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL,-49.8%; intermediate-density lipoprotein,-44.7%; LDL,-46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%). Conclusions-In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN.

U2 - 10.1161/ATVBAHA.115.306136

DO - 10.1161/ATVBAHA.115.306136

M3 - Article

VL - 35

SP - 2686

EP - 2693

JO - ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

JF - ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

SN - 1079-5642

IS - 12

ER -