Metabolic effect of decreasing nonesterified fatty acid levels with acipimox in hyperthyroid patients

Glucose intolerance is often found in patients with hyperthyroidism, but the pathogenetic mechanisms are not fully understood. Since lipolysis is increased in hyperthyroidism, elevated plasma nonesterified fatty acids (NEFAs) may contribute to abnormal glucose metabolism in hyperthyroidism. The aim of this study was to investigate whether decreasing the plasma NEFA level with acipimox can affect glucose metabolism in hyperthyroidism. We performed an intravenous glucose tolerance test (IVGTT) with acipimox 250 mg or placebo in six untreated hyperthyroid men and six age- and body mass index (BMI)-matched controls. Fasting plasma NEFA levels were significantly higher in the hyperthyroid patients versus the controls (997.0 ± 303.4 v 290.5 ± 169.1 μmol/L, P < .001). Plasma NEFAs decreased rapidly with acipimox treatment in both controls and hyperthyroid patients. In the controls, the glucose disappearance constant (KG) was not different for acipimox treatment versus placebo (2.18 ± 0.62 v 2.42 ± 1.00% · min−1). In hyperthyroid patients, acipimox treatment increased the KG significantly compared with placebo treatment (2.44 ± 0.84 v 1.58 ± 0.37% · min−1, P < .05). Changes in KG values with acipimox treatment were inversely correlated with changes in plasma NEFA levels (r = −.65, P < .05). Acipimox treatment increased the acute insulin response (AIR) in hyperthyroid patients (943 ± 381 v 698 ± 279 μU/mL · P < .05), whereas it did not change the AIR in controls. Changes in the AIR with acipimox treatment correlated significantly with changes in the KG (r = .70, P < .05). There was a weak correlation between changes in the AIR with acipimox treatment and changes in plasma NEFA levels (r = −.55, P = .06). In summary, decreasing the plasma NEFA level with acipimox in hyperthyroid patients increases both the KG and AIR during an IVGTT. These findings suggest that the abnormal glucose metabolism in hyperthyroidism could be attributed, at least in part, to the increase of plasma NEFA.