Acute administration of the antilipolytic
nicotinic acid analog
acipimox to patients with
noninsulin-dependent diabetes mellitus (
NIDDM) is associated with increased peripheral and hepatic
insulin sensitivity. However, long term
acipimox treatment (250 mg, 3 times/24 h) of
NIDDM patients does not improve
blood glucose control, possibly due to rebound lipolysis. The current study assessed the influence of intensified
acipimox administration (125 mg, 12 times/24 h) on diurnal plasma profiles of
glucose,
insulin, nonesterified FFA (
NEFA), and
triglycerides during a 3-day period. Eight
NIDDM patients [mean age, 58.9 yr (range, 46-68); mean body mass index, 31.4 kg/m2 (range, 24.9-39.6)] were included in a randomized, double blind, placebo-controlled, cross-over study. Blood samples were collected every second hour during the study. The
acipimox and placebo treatments were separated by a 2-week washout period.
Acipimox treatment was associated with reduced diurnal mean plasma concentrations of
NEFA [0.26 +/- 0.03 (+/- SEM) vs. 0.63 +/- 0.06 mmol/L; P < 0.001],
triglycerides (1.74 +/- 0.21 vs. 2.10 +/- 0.18 mmol/L; P < 0.03),
glucose (12.7 +/- 1.0 vs. 15.8 +/- 1.2 mmol/L; P < 0.002), and
insulin (157 +/- 21 vs. 207 +/- 27 pmol/L; P < 0.05). However, despite the overall reduction in mean
NEFA, during
acipimox treatment
NEFA increased from days 1-3 (0.18 +/- 0.03 vs. 0.34 +/- 0.04 mmol/L; P < 0.001), whereas plasma
glucose (13.4 +/- 1.2 vs. 12.3 +/- 0.9 mmol/L; P < 0.03) and plasma
insulin (168 +/- 23 vs. 148 +/- 17 pmol/L; P < 0.04) decreased steadily from days 1-3 during active treatment. In conclusion, inhibition of lipolysis using the intensified
acipimox treatment regiment was associated with a pronounced
blood glucose- and plasma
insulin-lowering effect. However, minor rebound effects of lipolysis occurred in some patients despite the presence of allegedly effective
acipimox levels. This suggests that caution should be employed concerning long term use of
acipimox as a
hypoglycemic agent in
NIDDM patients.