Park K S, Kim C H, Lee M K, Shin C S, Park D J, Kim S Y, Cho B Y, Lee H K
Department of Internal Medicine, Seoul National University College of Medicine, Chongno-Ku, South Korea.
Metabolism. 1999 Oct;48(10):1318-21. doi: 10.1016/s0026-0495(99)90274-3.
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 v290.5 +/- 169.1 micromol/L, P < .001). Plasma NEFAs decreased rapidly with acipimox treatment in both controls and hyperthyroid patients. In the controls, the glucose disappearance constant (K(G)) was not different for acipimox treatment versus placebo (2.18 +/- 0.62 v 2.42 +/- 1.00% x min(-1)). In hyperthyroid patients, acipimox treatment increased the K(G) significantly compared with placebo treatment (2.44 +/- 0.84 v 1.58 +/- 0.37% x min(-1), P < .05). Changes in K(G) 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 microU/mL x min, P < .05), whereas it did not change the AIR in controls. Changes in the AIR with acipimox treatment correlated significantly with changes in the K(G) (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 K(G) 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.
葡萄糖耐量异常在甲状腺功能亢进患者中较为常见，但其发病机制尚未完全明确。由于甲状腺功能亢进时脂解作用增强，血浆非酯化脂肪酸（NEFA）水平升高可能导致甲状腺功能亢进患者葡萄糖代谢异常。本研究旨在探讨使用阿西莫司降低血浆NEFA水平是否会影响甲状腺功能亢进患者的葡萄糖代谢。我们对6名未经治疗的甲状腺功能亢进男性患者和6名年龄及体重指数（BMI）匹配的对照者进行了静脉葡萄糖耐量试验（IVGTT），分别给予250mg阿西莫司或安慰剂。甲状腺功能亢进患者的空腹血浆NEFA水平显著高于对照组（997.0±303.4对290.5±169.1μmol/L，P<.001）。在对照组和甲状腺功能亢进患者中，阿西莫司治疗均使血浆NEFA迅速下降。在对照组中，阿西莫司治疗与安慰剂治疗的葡萄糖消失常数（K(G)）无差异（2.18±0.62对2.42±1.00%·min-1）。在甲状腺功能亢进患者中，与安慰剂治疗相比，阿西莫司治疗显著提高了K(G)（2.44±0.84对1.58±0.37%·min-1，P<.05）。阿西莫司治疗导致的K(G)值变化与血浆NEFA水平变化呈负相关（r = -.65，P<.05）。阿西莫司治疗使甲状腺功能亢进患者的急性胰岛素反应（AIR）增加（943±381对698±279μU/mL·min，P<.05），而对对照组的AIR无影响。阿西莫司治疗导致的AIR变化与K(G)变化显著相关（r =.70，P<.05）。阿西莫司治疗导致的AIR变化与血浆NEFA水平变化之间存在弱相关性（r = -.55，P =.06）。总之，甲状腺功能亢进患者使用阿西莫司降低血浆NEFA水平可使IVGTT期间的K(G)和AIR均增加。这些发现表明，甲状腺功能亢进患者的葡萄糖代谢异常至少部分可归因于血浆NEFA的增加。
