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

Aim

The nicotinic acid analogue acipimox is an anti-lipolytic 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 (GH) levels that reverse the anti-lipolytic effect of acipimox. Hypopituitary patients constitute a viable model to study the GH-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.

Methods

We studied heart rate variability (HRV) as a measure of autonomic tone in eight hypopituitary men with and without acipimox treatment. SDNN, RMSSD, and HF were measured as HRV parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on 2 occasions in a randomized, double blind and placebo controlled crossover study.

Results

Plasma glucose (4.7 vs. 4.9 mmol/l, P=0.02) and serum FFA (0.05 vs. 0.41 mmol/l, P<0.001) were significantly decreased during acipimox treatment. Acipimox had an inhibitory effect on SDNN (41.3 vs. 45.3 ms, P=0.01), RMSSD (23.2 vs. 11 ms, P=0.03), and HF (3.79 vs 3.60 ln(ms²), P=0.02) and these effects were reversed during clamping.

Conclusions

We showed that 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.

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