Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation.

Abstract

The nicotinic acid analogue acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with acipimox acutely affects autonomic tone. We studied heart rate variability as a measure of autonomic tone in eight hypopituitary men with and without acipimox treatment. The standard deviation of normal-to-normal intervals, root mean square of successive differences and high frequency were measured as heart rate variability parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on two occasions in a randomized, double-blind and placebo-controlled crossover study. Plasma glucose (4.7 vs. 4.9mmoll-1 , P=0.02) and serum FFA (0.05 vs. 0.41mmoll-1 , P<0.001) were significantly decreased during acipimox treatment. Acipimox had an inhibitory effect on standard deviation of normal-to-normal intervals (41.3 vs. 45.3ms, P=0.01), root mean square of successive differences (23.2 vs. 11ms, P=0.03) and high frequency (3.79 vs 3.60 ln (ms2 ), P=0.02) and these effects were reversed during clamping. Short-term inhibition of lipolysis by acipimox treatment lowered circulating FFA levels, improved insulin sensitivity, and was accompanied by reduced parasympathetic tone. The effect of acipimox on the parasympathetic modulation was reversed by hyperinsulinaemia.