Apolipoprotein M predicts pre-beta-HDL formation: studies in type 2 diabetic and nondiabetic subjects

P Plomgaard, R P F Dullaart, R de Vries, A K Groen, B Dahlbäck, L B Nielsen

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Abstract

OBJECTIVE: Studies in mice suggest that plasma apoM is lowered in hyperinsulinaemic diabetes and that apoM stimulates formation of pre-beta-HDL. Pre-beta-HDL is an acceptor of cellular cholesterol and may be critical for reverse cholesterol transport. Herein, we examined whether patients with type 2 diabetes have reduced plasma apoM and whether apoM is associated with pre-beta-HDL formation and cellular cholesterol efflux. DESIGN: In 78 patients with type 2 diabetes and 89 control subjects, we measured plasma apoM with ELISA, pre-beta-HDL and pre-beta-HDL formation, phospholipid transfer protein (PLTP) activity and the ability of plasma to promote cholesterol efflux from cultured fibroblasts. RESULTS: ApoM was approximately 9% lower in patients with type 2 diabetes compared to controls (0.025 +/- 0.006 vs. 0.027 +/- 0.007 g L(-1), P = 0.01). The difference in apoM was largely attributable to diabetes-associated obesity. ApoM was positively related to both HDL (r = 0.16; P = 0.04) and LDL cholesterol (r = 0.28; P = 0.0003). Pre-beta-HDL and pre-beta-HDL formation were not different between diabetic and control subjects. ApoM predicted pre-beta-HDL (r = 0.16; P = 0.04) and pre-beta-HDL formation (r = 0.19; P = 0.02), even independently of positive relationships with apoA-I, HDL-cholesterol and PLTP activity. Cellular cholesterol efflux to plasma was positively related to pre-beta-HDL and PLTP activity but not significantly to apoM. CONCLUSIONS: Plasma apoM is modestly reduced in type 2 diabetes. Pre-beta-HDL and pre-beta-HDL formation are positively associated with apoM, supporting the hypothesis that apoM plays a role in HDL remodelling in humans. Lower apoM may provide a mechanism to explain why pre-beta-HDL formation is not increased in type 2 diabetes despite elevated PLTP activity.
Original languageEnglish
JournalJournal of Internal Medicine
Volume266
Issue number3
Pages (from-to)258-67
Number of pages9
ISSN0954-6820
DOIs
Publication statusPublished - 2009

Bibliographical note

Keywords: Aged; Apolipoprotein A-I; Apolipoproteins; Biological Markers; Case-Control Studies; Cells, Cultured; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Female; Fibroblasts; High-Density Lipoproteins, Pre-beta; Humans; Linear Models; Male; Metabolic Syndrome X; Middle Aged; Phospholipid Transfer Proteins; Statistics, Nonparametric

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