Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders

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• 作者：Daiana Ibarretxe^a ; ^c ; Josefa Girona^a ; ^c ; Nú ; ria Plana^a ; ^c ; Anna Cabré ; ^a ; ^c ; Raimó ; n Ferré ; ^a ; ^c ; Nú ; ria Amigó ; ^b ; ^c ; Sandra Guaita^a ; ^c ; Roger Mallol^b ; ^c ; Mercedes Heras^a ; ^c ; Luis Masana^a ; ^c ; ^{luis.masana@urv.cat" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PCSK9 ; Type 2 diabetes ; Metabolic syndrome ; Nuclear magnetic resonance ; SNP
• 刊名：Clínica e Investigación en Arteriosclerosis
• 出版年：2016
• 出版时间：March-April 2016
• 年：2016
• 卷：28
• 期：2
• 页码：71-78
• 全文大小：790 K

文摘

PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis.

Methods

There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients.

Results

The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%; p&#xA0;<&#xA0;0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C).

Conclusions

PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism.