Davoren P M, Kelly W, Gries F A, Hubinger A, Whately-Smith C, Alberti K G
Human Diabetes and Metabolism Research Centre, University of Newcastle upon Tyne, UK.
Metabolism. 1998 Mar;47(3):250-6. doi: 10.1016/s0026-0495(98)90252-9.
Elevated circulating plasma nonesterified fatty acids (NEFA) may contribute to the insulin resistance and hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM), and decreasing plasma NEFA could provide a therapeutic benefit. A sustained-release preparation of acipimox, a lipolysis inhibitor, was used in an attempt to decrease circulating plasma NEFA levels long-term, and the effects on glycemic control, insulin resistance, and serum lipids were measured. Sixty NIDDM patients (43 males and 17 females) took part in a randomized controlled trial of acipimox or placebo for 12 weeks. Fasting plasma NEFA levels did not change in acipimox-treated patients (baseline v 12 weeks, 0.84 +/- 0.35 v 0.88 +/- 0.55 mmol x L(-1), mean +/- SD). Fasting blood glucose was unchanged (mean difference v placebo, -0.5 mmol x L(-1); 95% confidence interval [CI], -1.4 to 0.3 mmol x L[-1]), but serum fructosamine decreased (mean difference v placebo, -26 micromol x L(-1); 95% CI, -51 to 0 mmol x L[-1]), as did the standardized hemoglobin A1 ([HbA1] mean difference v placebo, -1.4%; 95% CI, -3.0% to -0.1%). Insulin resistance measured as steady-state plasma glucose during an insulin-dextrose infusion test was unchanged (mean difference v placebo, -1.4 mmol x L(-1); 95% CI, -3.2 to 0.5 mmol x L[-1]). Serum total cholesterol (mean difference v placebo, -0.4 mmol x L(-1); 95% CI, -0.6 to -0.1 mmol x L[-1]), serum apolipoprotein B ([apo B] mean difference v placebo, -0.19 g x L(-1); 95% CI, -0.3 to -0.1 g x L[-1]), and serum triglycerides (mean difference v placebo for pretreatment v posttreatment ratio, 0.59; 95% CI, 0.40 to 0.88) were all lower with acipimox. Serum high-density lipoprotein (HDL) cholesterol (mean difference v placebo, 0.10 mmol x L(-1); 95% CI, -0.05 to 0.3 mmol x L[-1]), serum apo A1 (mean difference v placebo, 0.03 g x L(-1); 95% CI, -0.04 to 0.1 g x L[-1]), and serum lipoprotein(a) ([Lp(a)] acipimox v placebo, 154 (0 to 1,574) v 71 (0 to 1,009), median and range) were unchanged. Despite the lack of change in fasting plasma NEFA levels, acipimox caused a modest beneficial improvement in overall glycemic control and plasma lipids in NIDDM patients and could be a useful agent in the treatment of dyslipidemic NIDDM patients.
循环血浆中非酯化脂肪酸（NEFA）水平升高可能会导致非胰岛素依赖型糖尿病（NIDDM）的胰岛素抵抗和高血糖，降低血浆NEFA水平可能会带来治疗益处。使用了一种脂解抑制剂阿西莫司的缓释制剂，试图长期降低循环血浆NEFA水平，并测量其对血糖控制、胰岛素抵抗和血脂的影响。60例NIDDM患者（43例男性和17例女性）参与了一项阿西莫司或安慰剂的随机对照试验，为期12周。接受阿西莫司治疗的患者空腹血浆NEFA水平没有变化（基线值与12周时相比，分别为0.84±0.35和0.88±0.55 mmol/L，均值±标准差）。空腹血糖没有变化（与安慰剂相比的均值差异为-0.5 mmol/L；95%置信区间[CI]为-1.4至0.3 mmol/L），但血清果糖胺降低（与安慰剂相比的均值差异为-26 μmol/L；95% CI为-51至0 μmol/L），糖化血红蛋白A1（[HbA1]与安慰剂相比的均值差异为-1.4%；95% CI为-3.0%至-0.1%）也降低。在胰岛素-葡萄糖输注试验中，以稳态血浆葡萄糖衡量的胰岛素抵抗没有变化（与安慰剂相比的均值差异为-1.4 mmol/L；95% CI为-3.2至0.5 mmol/L）。阿西莫司治疗后，血清总胆固醇（与安慰剂相比的均值差异为-0.4 mmol/L；95% CI为-0.6至-0.1 mmol/L）、血清载脂蛋白B（[apo B]与安慰剂相比的均值差异为-0.19 g/L；95% CI为-0.3至-0.1 g/L）以及血清甘油三酯（治疗前与治疗后比值与安慰剂相比的均值差异为0.59；95% CI为0.40至0.88）均降低。血清高密度脂蛋白（HDL）胆固醇（与安慰剂相比的均值差异为0.10 mmol/L；95% CI为-0.05至0.3 mmol/L）、血清载脂蛋白A1（与安慰剂相比的均值差异为0.03 g/L；95% CI为-0.04至0.1 g/L）以及血清脂蛋白(a)（[Lp(a)]阿西莫司组与安慰剂组相比，中位数和范围分别为154（0至1574）和71（0至1009））没有变化。尽管空腹血浆NEFA水平没有变化，但阿西莫司使NIDDM患者的总体血糖控制和血脂有适度的有益改善，可能是治疗血脂异常的NIDDM患者的一种有用药物。
