INSERM CRI 866, CHU Bocage, Dijon, France.
Atherosclerosis. 2011 Nov;219(1):342-8. doi: 10.1016/j.atherosclerosis.2011.07.098. Epub 2011 Jul 26.
Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a post-transcriptional inhibitor of LDL-receptor. In non-diabetic men, plasma PCSK9 levels were found to be inversely correlated with low-density lipoprotein (LDL) apolipoprotein B100 (apoB) fractional catabolic rate (FCR). Here, we aimed to determine the effect of type 2 diabetes on the association between plasma PCSK9 and FCR of LDL.
A kinetic study of LDL-apoB100, using stable isotopes, was performed in 38 individuals (20 men, 18 women) including 23 non-diabetic normolipidemic subjects and 15 patients with type 2 diabetes.
In the non-diabetic group, plasma PCSK9 was positively correlated with LDL-C (r=0.64, p=0.001), apoB (r=0.67, p<0.001), and inversely correlated with LDL-apoB FCR (r=-0.61, p=0.002). In contrast, in type 2 diabetic patients, plasma PCSK9 was not associated with LDL-C, apoB and LDL-apoB FCR. However, the lack of association between PCSK9 and LDL-apoB FCR seemed to be limited to the patients with "uncontrolled" diabetes (HbA1c>7%) since a borderline significant negative correlation between PCSK9 and LDL FCR (r=-0.70, p=0.08) was retrieved in patients with HbA1c≤7%. In multivariate analysis, LDL-apoB FCR was independently associated with PCSK9 (p=0.001) and fasting glycaemia (log) (p=0.030) in the non-diabetic population and with PCSK9 (p=0.040) and HbA1c (p=0.029) in diabetic patients.
Our data indicate that both PCSK9 and glycaemia are independent factors influencing LDL catabolism. Plasma PCSK9 influences significantly the catabolism of LDL-apoB100 in individuals without diabetes, but not in patients with uncontrolled type 2 diabetes. Thus, the influence of diabetes on LDL-apoB FCR catabolism may overwhelm the influence of PCSK9.
前蛋白转化酶枯草溶菌素 9（PCSK9）是 LDL 受体的转录后抑制剂。在非糖尿病男性中，发现血浆 PCSK9 水平与 LDL 载脂蛋白 B100（apoB）的半衰期（FCR）呈负相关。在此，我们旨在确定 2 型糖尿病对血浆 PCSK9 与 LDL FCR 之间的关联的影响。
对 38 名个体（20 名男性，18 名女性）进行了 LDL-apoB100 的动力学研究，其中包括 23 名非糖尿病血脂正常的受试者和 15 名 2 型糖尿病患者。
在非糖尿病组中，血浆 PCSK9 与 LDL-C（r=0.64，p=0.001）、apoB（r=0.67，p<0.001）呈正相关，与 LDL-apoB FCR（r=-0.61，p=0.002）呈负相关。相反，在 2 型糖尿病患者中，血浆 PCSK9 与 LDL-C、apoB 和 LDL-apoB FCR 无关。然而，PCSK9 与 LDL-apoB FCR 之间的缺乏关联似乎仅限于“未控制”糖尿病患者（HbA1c>7%），因为在 HbA1c≤7%的患者中，PCSK9 与 LDL FCR 之间存在临界显著的负相关（r=-0.70，p=0.08）。在多元分析中，LDL-apoB FCR 与 PCSK9（p=0.001）和空腹血糖（log）（p=0.030）在非糖尿病人群中独立相关，与 PCSK9（p=0.040）和 HbA1c（p=0.029）在糖尿病患者中独立相关。
我们的数据表明，PCSK9 和血糖都是影响 LDL 代谢的独立因素。在没有糖尿病的个体中，PCSK9 显著影响 LDL-apoB100 的代谢，但在未控制的 2 型糖尿病患者中则不然。因此，糖尿病对 LDL-apoB FCR 代谢的影响可能超过 PCSK9 的影响。
