Effect of niacin on high-density lipoprotein apolipoprotein A-I kinetics in statin-treated patients with type 2 diabetes mellitus

Jing Pang, Dick Chan, Sandy Hamilton, V.S. Tenneti, Gerald Watts, Hugh Barrett

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

OBJECTIVE - : To investigate the effect of extended-release (ER) niacin on the metabolism of high-density lipoprotein (HDL) apolipoprotein A-I (apoA-I) in men with type 2 diabetes mellitus on a background of optimal statin therapy.

APPROACH AND RESULTS - : Twelve men with type 2 diabetes mellitus were recruited for a randomized, crossover design trial. Patients were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed over to the alternate therapy after a 3-week washout period. Metabolic studies were performed at the end of each treatment period. HDL apoA-I kinetics were measured after a standardized liquid mixed meal and a bolus injection of d3-leucine for 96 hours. Compartmental analysis was used to model the data. ER niacin significantly decreased plasma triglyceride, plasma cholesterol, non-HDL cholesterol, low-density lipoprotein cholesterol, and apoB (all P<0.05) and significantly increased HDL cholesterol and apoA-I concentrations (P<0.005 and P<0.05, respectively). ER niacin also significantly increased HDL apoA-I pool size (6088±292 versus 5675±305 mg; P<0.001), and this was attributed to a lower HDL apoA-I fractional catabolic rate (0.33±0.01 versus 0.37±0.02 pools/d; P<0.005), with no significant changes in HDL apoA-I production (20.93±0.63 versus 21.72±0.85 mg/kg per day; P=0.28).

Conclusions—ER niacin increases HDL apoA-I concentration in statin-treated subjects with type 2 diabetes mellitus by lowering apoA-I fractional catabolic rate. The effect on HDL metabolism was independent of the reduction in plasma triglyceride with ER niacin treatment. Whether this finding applies to other dyslipidemic populations remains to be investigated.
Original languageEnglish
Pages (from-to)427-432
JournalArteriosclerosis, thrombosis, and vascular biology
Volume34
Issue number2
Early online date27 Nov 2013
DOIs
Publication statusPublished - Feb 2014

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Niacin
Apolipoprotein A-I
HDL Lipoproteins
Type 2 Diabetes Mellitus
Cross-Over Studies
Triglycerides
lipoprotein A-I
Apolipoproteins B
Therapeutics
Leucine
LDL Cholesterol
HDL Cholesterol
Meals
Cholesterol
Injections

Cite this

@article{ece0633128fe42de9a2bf356f64bfd38,
title = "Effect of niacin on high-density lipoprotein apolipoprotein A-I kinetics in statin-treated patients with type 2 diabetes mellitus",
abstract = "OBJECTIVE - : To investigate the effect of extended-release (ER) niacin on the metabolism of high-density lipoprotein (HDL) apolipoprotein A-I (apoA-I) in men with type 2 diabetes mellitus on a background of optimal statin therapy. APPROACH AND RESULTS - : Twelve men with type 2 diabetes mellitus were recruited for a randomized, crossover design trial. Patients were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed over to the alternate therapy after a 3-week washout period. Metabolic studies were performed at the end of each treatment period. HDL apoA-I kinetics were measured after a standardized liquid mixed meal and a bolus injection of d3-leucine for 96 hours. Compartmental analysis was used to model the data. ER niacin significantly decreased plasma triglyceride, plasma cholesterol, non-HDL cholesterol, low-density lipoprotein cholesterol, and apoB (all P<0.05) and significantly increased HDL cholesterol and apoA-I concentrations (P<0.005 and P<0.05, respectively). ER niacin also significantly increased HDL apoA-I pool size (6088±292 versus 5675±305 mg; P<0.001), and this was attributed to a lower HDL apoA-I fractional catabolic rate (0.33±0.01 versus 0.37±0.02 pools/d; P<0.005), with no significant changes in HDL apoA-I production (20.93±0.63 versus 21.72±0.85 mg/kg per day; P=0.28). Conclusions—ER niacin increases HDL apoA-I concentration in statin-treated subjects with type 2 diabetes mellitus by lowering apoA-I fractional catabolic rate. The effect on HDL metabolism was independent of the reduction in plasma triglyceride with ER niacin treatment. Whether this finding applies to other dyslipidemic populations remains to be investigated.",
author = "Jing Pang and Dick Chan and Sandy Hamilton and V.S. Tenneti and Gerald Watts and Hugh Barrett",
year = "2014",
month = "2",
doi = "10.1161/ATVBAHA.113.302019",
language = "English",
volume = "34",
pages = "427--432",
journal = "ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY",
issn = "1079-5642",
publisher = "Lippincott Williams & Wilkins",
number = "2",

}

TY - JOUR

T1 - Effect of niacin on high-density lipoprotein apolipoprotein A-I kinetics in statin-treated patients with type 2 diabetes mellitus

AU - Pang, Jing

AU - Chan, Dick

AU - Hamilton, Sandy

AU - Tenneti, V.S.

AU - Watts, Gerald

AU - Barrett, Hugh

PY - 2014/2

Y1 - 2014/2

N2 - OBJECTIVE - : To investigate the effect of extended-release (ER) niacin on the metabolism of high-density lipoprotein (HDL) apolipoprotein A-I (apoA-I) in men with type 2 diabetes mellitus on a background of optimal statin therapy. APPROACH AND RESULTS - : Twelve men with type 2 diabetes mellitus were recruited for a randomized, crossover design trial. Patients were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed over to the alternate therapy after a 3-week washout period. Metabolic studies were performed at the end of each treatment period. HDL apoA-I kinetics were measured after a standardized liquid mixed meal and a bolus injection of d3-leucine for 96 hours. Compartmental analysis was used to model the data. ER niacin significantly decreased plasma triglyceride, plasma cholesterol, non-HDL cholesterol, low-density lipoprotein cholesterol, and apoB (all P<0.05) and significantly increased HDL cholesterol and apoA-I concentrations (P<0.005 and P<0.05, respectively). ER niacin also significantly increased HDL apoA-I pool size (6088±292 versus 5675±305 mg; P<0.001), and this was attributed to a lower HDL apoA-I fractional catabolic rate (0.33±0.01 versus 0.37±0.02 pools/d; P<0.005), with no significant changes in HDL apoA-I production (20.93±0.63 versus 21.72±0.85 mg/kg per day; P=0.28). Conclusions—ER niacin increases HDL apoA-I concentration in statin-treated subjects with type 2 diabetes mellitus by lowering apoA-I fractional catabolic rate. The effect on HDL metabolism was independent of the reduction in plasma triglyceride with ER niacin treatment. Whether this finding applies to other dyslipidemic populations remains to be investigated.

AB - OBJECTIVE - : To investigate the effect of extended-release (ER) niacin on the metabolism of high-density lipoprotein (HDL) apolipoprotein A-I (apoA-I) in men with type 2 diabetes mellitus on a background of optimal statin therapy. APPROACH AND RESULTS - : Twelve men with type 2 diabetes mellitus were recruited for a randomized, crossover design trial. Patients were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed over to the alternate therapy after a 3-week washout period. Metabolic studies were performed at the end of each treatment period. HDL apoA-I kinetics were measured after a standardized liquid mixed meal and a bolus injection of d3-leucine for 96 hours. Compartmental analysis was used to model the data. ER niacin significantly decreased plasma triglyceride, plasma cholesterol, non-HDL cholesterol, low-density lipoprotein cholesterol, and apoB (all P<0.05) and significantly increased HDL cholesterol and apoA-I concentrations (P<0.005 and P<0.05, respectively). ER niacin also significantly increased HDL apoA-I pool size (6088±292 versus 5675±305 mg; P<0.001), and this was attributed to a lower HDL apoA-I fractional catabolic rate (0.33±0.01 versus 0.37±0.02 pools/d; P<0.005), with no significant changes in HDL apoA-I production (20.93±0.63 versus 21.72±0.85 mg/kg per day; P=0.28). Conclusions—ER niacin increases HDL apoA-I concentration in statin-treated subjects with type 2 diabetes mellitus by lowering apoA-I fractional catabolic rate. The effect on HDL metabolism was independent of the reduction in plasma triglyceride with ER niacin treatment. Whether this finding applies to other dyslipidemic populations remains to be investigated.

U2 - 10.1161/ATVBAHA.113.302019

DO - 10.1161/ATVBAHA.113.302019

M3 - Article

VL - 34

SP - 427

EP - 432

JO - ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

JF - ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

SN - 1079-5642

IS - 2

ER -