Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
J Clin Endocrinol Metab. 2018 Nov 1;103(11):4176-4186. doi: 10.1210/jc.2018-01446.
3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are widely prescribed. Statins may have important metabolic effects on insulin sensitivity and liver fat, but limited studies have assessed these effects by using euglycemic hyperinsulinemic clamp, stable isotopes, and 1H magnetic resonance spectroscopy (MRS) for liver fat quantification.
To study the effects of pitavastatin on hepatic fat and insulin sensitivity.
Six-month, double-blind, randomized, placebo-controlled trial.
Academic clinical research center in Boston, Massachusetts.
Overweight, insulin-resistant men aged 40 to 65 years who had not received statin therapy for ≥1 year.
Pitavastatin 4 mg or placebo daily.
The primary endpoints were changes in insulin sensitivity measured by euglycemic hyperinsulinemic clamp and liver fat measured by 1H MRS.
Pitavastatin showed no effect on endogenous glucose production (ΔRa glucose 0.07 ± 0.07 vs 0.04 ± 0.07 mg/kg/min, pitavastatin vs placebo, P = 0.76) or insulin-stimulated glucose uptake during "low dose" (ΔM 0.1 ± 0.1 vs -0.3 ± 0.2 mg/kg/min, P = 0.11) and "high dose" (ΔM -0.5 ± 0.3 vs -0.7 ± 0.4 mg/kg/min, P = 0.70) euglycemic hyperinsulinemic clamps. There was also no effect of pitavastatin on fasting glucose, HbA1c, and 2-hour glucose after 75-g glucose challenge. There was also no change in liver fat fraction (-1 ± 1 vs -0 ± 1%, P = 0.56).
Compared with placebo, pitavastatin did not affect hepatic or whole-body insulin sensitivity, and it did not reduce liver fat.
3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂（他汀类药物）被广泛应用。他汀类药物可能对胰岛素敏感性和肝脏脂肪产生重要的代谢作用，但通过使用正葡萄糖高胰岛素钳夹、稳定同位素和 1H 磁共振波谱（MRS）进行肝脏脂肪定量评估这些作用的研究有限。
研究匹伐他汀对肝脏脂肪和胰岛素敏感性的影响。
为期 6 个月的、双盲、随机、安慰剂对照试验。
马萨诸塞州波士顿的学术临床研究中心。
超重、胰岛素抵抗的年龄在 40 至 65 岁之间的男性，他们在过去 1 年内未接受过他汀类药物治疗。
每天给予匹伐他汀 4 毫克或安慰剂。
通过正葡萄糖高胰岛素钳夹测量的胰岛素敏感性变化和通过 1H MRS 测量的肝脏脂肪变化。
匹伐他汀对内源性葡萄糖生成（ΔRa 葡萄糖 0.07 ± 0.07 对 0.04 ± 0.07 mg/kg/min，匹伐他汀对安慰剂，P = 0.76）或“低剂量”（ΔM 0.1 ± 0.1 对-0.3 ± 0.2 mg/kg/min，P = 0.11）和“高剂量”（ΔM -0.5 ± 0.3 对-0.7 ± 0.4 mg/kg/min，P = 0.70）正葡萄糖高胰岛素钳夹期间胰岛素刺激的葡萄糖摄取没有影响。匹伐他汀对空腹血糖、HbA1c 和 75 克葡萄糖负荷后 2 小时血糖也没有影响。肝脏脂肪分数也没有变化（-1 ± 1 对 0 ± 1%，P = 0.56）。
与安慰剂相比，匹伐他汀对肝脏或全身胰岛素敏感性没有影响，也没有降低肝脏脂肪。
