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


METHODS
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.
Plomgaard
P
P
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Dullaart
R P F
RP
de Vries
R
R
Groen
A K
AK
Dahlbäck
B
B
Nielsen
L B
LB
D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D001053:Apolipoproteins / Q000097:blood*; D000075243:Apolipoproteins M; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D053442:High-Density Lipoproteins, Pre-beta / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D016014:Linear Models; D054834:Lipocalins; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins / Q000097:blood; D018709:Statistics, Nonparametric
C400523:APOM protein, human; D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D015415:Biomarkers; D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; D054834:Lipocalins; D049294:Phospholipid Transfer Proteins; D002784:Cholesterol