Short-term Acipimox decreases the ability of plasma from Type 2 diabetic patients and healthy subjects to stimulate cellular cholesterol efflux: a potentially adverse effect on reverse cholesterol transport.
OBJECTIVE
To evaluate the effect of short-term administration of the anti-lipolytic agent, Acipimox, on the ability of plasma to stimulate cellular cholesterol removal, which represents one of the first steps in the anti-atherogenic process of reverse cholesterol transport.


METHODS
Eight male Type 2 diabetic patients and eight healthy subjects were studied after a 12-h fast at baseline, after 24 h of Acipimox administration, 250 mg every 4 h, and again after 1 week (recovery). Plasma lipids, apolipoprotein AI, phospholipid transfer protein (PLTP) activity, pre-beta high-density lipoproteins (HDL) in incubated plasma and efflux of radiolabelled cholesterol from Fu5AH rat hepatoma cells to plasma were measured at each time point.


RESULTS
Acipimox lowered plasma triglycerides in diabetic patients (P = 0.001) and healthy subjects (P = 0.002), whereas plasma non-esterified fatty acids were decreased in diabetic patients (P = 0.001) compared with the averaged values at baseline and recovery. Acipimox decreased HDL cholesterol in healthy subjects (P = 0.007) and plasma apolipoprotein AI in both groups (P = 0.001 for diabetic patients; P = 0.008 for healthy subjects). Not only plasma PLTP activity (P = 0.001 for diabetic patients; P = 0.01 for healthy subjects), but also pre-beta HDL in incubated plasma (P = 0.001 for diabetic patients; P = 0.03 for healthy subjects) and cellular cholesterol efflux to plasma (P = 0.04 for diabetic patients; P = 0.005 for healthy subjects) were lowered by Acipimox in both groups.


CONCLUSIONS
Short-term Acipimox administration impairs the ability of plasma from Type 2 diabetic patients and healthy subjects to stimulate cellular cholesterol efflux, in conjunction with alterations in HDL parameters and in PLTP activity. If the impairment of cellular cholesterol efflux to plasma is sustained with long-term treatment, this potentially adverse effect should be considered when treating diabetic dyslipidaemia with Acipimox. Diabet. Med. 18, 509-513 (2001)
Dullaart
R P
RP
Department of Endocrinology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. r.p.f.dullaart@int.azg.nl
van Tol
A
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D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D015992:Body Mass Index; D002352:Carrier Proteins / Q000097:blood; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000097:blood; D008114:Liver Neoplasms, Experimental; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D012016:Reference Values; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D002352:Carrier Proteins; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D053442:High-Density Lipoproteins, Pre-beta; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D011719:Pyrazines; D002784:Cholesterol; C027696:acipimox