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

Daiana Ibarretxe; Josefa Girona; Núria Plana; Anna Cabré; Raimón Ferré; Núria Amigó; Sandra Guaita; Roger Mallol; Mercedes Heras; Luis Masana

doi:10.1016/j.arteri.2015.11.001

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

Daiana Ibarretxe, Josefa Girona, Núria Plana, Anna Cabré, Raimón Ferré, Núria Amigó, Sandra Guaita, Roger Mallol, Mercedes Heras, Luis Masana

Research output: Indexed journal article › Article › peer-review

40 Citations (Scopus)

Abstract

Background: 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 < 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.

Original language	English
Pages (from-to)	71-78
Number of pages	8
Journal	Clínica e investigacion en arteriosclerosis
Volume	28
Issue number	2
DOIs	https://doi.org/10.1016/j.arteri.2015.11.001
Publication status	Published - 1 Mar 2016
Externally published	Yes

Keywords

Metabolic syndrome
Nuclear magnetic resonance
PCSK9
SNP
Type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.arteri.2015.11.001

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@article{e52e094c8c4c45ef921c295701c9a22e,

title = "Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders",

abstract = "Background: 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 < 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.",

keywords = "Metabolic syndrome, Nuclear magnetic resonance, PCSK9, SNP, Type 2 diabetes",

author = "Daiana Ibarretxe and Josefa Girona and N{\'u}ria Plana and Anna Cabr{\'e} and Raim{\'o}n Ferr{\'e} and N{\'u}ria Amig{\'o} and Sandra Guaita and Roger Mallol and Mercedes Heras and Luis Masana",

note = "Funding Information: This work was supported by grants from the Spanish Atherosclerosis Society . PCSK9 como marcador del patr{\'o}n metabol{\'o}mico asociado a la dislipemia aterog{\'e}nica. Relaci{\'o}n con la arteriosclerosis subcl{\'i}nica. Beca FEA/SEA 2012 Investigaci{\'o}n cl{\'i}nico-epidemiol{\'o}gica presented at the XXV SEA Congress, 2012. Spanish Atherosclerosis Society to Anna Cabr{\'e}. Funding Information: This study was funded in part by CIBERDEM and FIS-PI11/02216 and FEDER founds. Publisher Copyright: {\textcopyright} 2015 Sociedad Espa{\~n}ola de Arteriosclerosis.",

year = "2016",

month = mar,

day = "1",

doi = "10.1016/j.arteri.2015.11.001",

language = "English",

volume = "28",

pages = "71--78",

journal = "Cl{\'i}nica e investigacion en arteriosclerosis",

issn = "0214-9168",

publisher = "Sociedad Espanola de Arteriosclerosis",

number = "2",

}

TY - JOUR

T1 - Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders

AU - Ibarretxe, Daiana

AU - Girona, Josefa

AU - Plana, Núria

AU - Cabré, Anna

AU - Ferré, Raimón

AU - Amigó, Núria

AU - Guaita, Sandra

AU - Mallol, Roger

AU - Heras, Mercedes

AU - Masana, Luis

N1 - Funding Information: This work was supported by grants from the Spanish Atherosclerosis Society . PCSK9 como marcador del patrón metabolómico asociado a la dislipemia aterogénica. Relación con la arteriosclerosis subclínica. Beca FEA/SEA 2012 Investigación clínico-epidemiológica presented at the XXV SEA Congress, 2012. Spanish Atherosclerosis Society to Anna Cabré. Funding Information: This study was funded in part by CIBERDEM and FIS-PI11/02216 and FEDER founds. Publisher Copyright: © 2015 Sociedad Española de Arteriosclerosis.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background: 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 < 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.

AB - Background: 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 < 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.

KW - Metabolic syndrome

KW - Nuclear magnetic resonance

KW - PCSK9

KW - SNP

KW - Type 2 diabetes

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DO - 10.1016/j.arteri.2015.11.001

M3 - Article

C2 - 26743379

AN - SCOPUS:84952006078

SN - 0214-9168

VL - 28

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JO - Clínica e investigacion en arteriosclerosis

JF - Clínica e investigacion en arteriosclerosis

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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