AIM Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear. MATERIAL AND METHODS Twelve male patients with T2DM on an intensive insulin regimen completed a 6-week randomized, double-blind, placebo-controlled, proof-of-concept study. Participants received three biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated. RESULTS Alirocumab treatment reduced fasting plasma TG levels (between group median change -24.7%; P = 0.018) and fasting apoB48 serum levels (-35.9%; P = 0.039) compared with placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (-26.4%; P = 0.006) and apoB48 AUC (-55.7%; P = 0.046), as well as plasma TG incremental AUC (-21.4%; P = 0.04) and apoB48 incremental AUC (-26.8%; P = 0.02). In addition, alirocumab reduced fasting and postprandial TG levels in very low-density lipoprotein (VLDL) and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed. CONCLUSIONS In addition to the well-known LDL-C-reducing effects, 6 weeks of alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants.

中文翻译：

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在接受胰岛素治疗的2型糖尿病患者中，alirocumab对餐后脂质和血管弹性的安慰剂对照概念验证研究。

AIM 2型糖尿病（T2DM）与与动脉粥样硬化性血脂异常和餐后高脂血症相关的心血管疾病（CVD）风险增加有关。Alirocumab是一种前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）抑制剂，可通过降低低密度脂蛋白胆固醇（LDL-C）的浓度来提高CVD风险。但是，PCK9抑制剂对糖尿病性血脂异常的其他方面（尤其是餐后情况）的作用尚不清楚。材料和方法采用强化胰岛素治疗的12名男性T2DM患者完成了为期6周的随机，双盲，安慰剂对照，概念验证研究。参与者每两周服用三剂皮下阿罗罗单抗（150 mg）或安慰剂。干预前后，空腹和餐后甘油三酸酯（TG）的血浆水平，评估了载脂蛋白（apo）B48，超速离心分离的脂蛋白组成，血管功能和炎症标志物。结果与安慰剂相比，Alirocumab治疗降低了空腹血浆TG水平（组中位变化-24.7％； P = 0.018）和空腹apoB48血清水平（-35.9％； P = 0.039）。Alirocumab降低了曲线下的血浆TG面积（AUC）（-26.4％; P = 0.006）和apoB48 AUC（-55.7％; P = 0.046），以及血浆TG增量AUC（-21.4％; P = 0.04）和apoB48递增的AUC（-26.8％； P = 0.02）。此外，alirocumab降低了极低密度脂蛋白（VLDL）和LDL中的禁食和餐后TG水平。Alirocumab改善了空腹脉搏波速度，但未观察到餐后炎症标志的变化。结论除了众所周知的降低LDL-C的作用，