Association between proprotein convertase subtilisin/kexin 9 (PCSK9) and lipoprotein subclasses in children with type 1 diabetes mellitus: Effects of glycemic control.
Adolescent
Blood Glucose
/ metabolism
Cardiovascular Diseases
/ blood
Child
Cholesterol
/ blood
Cholesterol, HDL
/ blood
Cholesterol, LDL
/ blood
Cross-Sectional Studies
Diabetes Mellitus, Type 1
/ blood
Dyslipidemias
/ blood
Female
Humans
Insulin
/ therapeutic use
Lipoproteins, HDL
/ metabolism
Lipoproteins, LDL
/ metabolism
Male
Multivariate Analysis
Proprotein Convertase 9
/ blood
Dense LDL
Dyslipidemia
Glucoregulation
HDL
PCSK9
Small
Type 1 diabetes
Journal
Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
11
06
2018
revised:
01
10
2018
accepted:
08
11
2018
pubmed:
20
11
2018
medline:
25
3
2020
entrez:
20
11
2018
Statut:
ppublish
Résumé
Dyslipidemia in type 1 diabetes mellitus (T1DM) is characterised by altered distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses. Recent studies suggested that proprotein convertase subtilisin/kexin 9 (PCSK9) may contribute to the development of dyslipidemia in T1DM. In this cross-sectional study, we investigated the association between PCSK9 and lipoprotein subclasses in young T1DM patients, with respect to glycemic control. Plasma PCSK9 and lipoprotein subclasses were determined in 207 patients with T1DM (106 boys and 101 girls), aged 13.9 ± 3.0 years and treated by intensive insulin therapy. Plasma PCSK9 levels significantly increased with worsening of glycemic control (p < 0.001). T1DM patients with poor glucoregulation had the highest proportion of small, dense LDL (sdLDL) and smaller HDL particles, as well. PCSK9 was positively associated with markers of glucose homeostasis and serum lipid parameters only in patients with suboptimal/poor glucoregulation. In well-controlled T1DM, plasma PCSK9 level was inversely associated with a relative proportion of sdLDL particles (p < 0.01) and this association remained significant in multivariate analysis. In T1DM patients with suboptimal/poor glycemic control, PCSK9 was positively associated with the proportion of the smallest HDL3c particles (p < 0.001), but negatively with HDL size (p < 0.05). The extent of achieved metabolic control modifies the association between PCSK9 and lipoprotein subclasses in T1DM. Further investigations are needed to reveal whether the observed effects of glycemic control on PCSK9 and sdLDL levels have causal consequences on CVD risk in young patients with T1DM.
Sections du résumé
BACKGROUND AND AIMS
Dyslipidemia in type 1 diabetes mellitus (T1DM) is characterised by altered distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses. Recent studies suggested that proprotein convertase subtilisin/kexin 9 (PCSK9) may contribute to the development of dyslipidemia in T1DM. In this cross-sectional study, we investigated the association between PCSK9 and lipoprotein subclasses in young T1DM patients, with respect to glycemic control.
METHODS
Plasma PCSK9 and lipoprotein subclasses were determined in 207 patients with T1DM (106 boys and 101 girls), aged 13.9 ± 3.0 years and treated by intensive insulin therapy.
RESULTS
Plasma PCSK9 levels significantly increased with worsening of glycemic control (p < 0.001). T1DM patients with poor glucoregulation had the highest proportion of small, dense LDL (sdLDL) and smaller HDL particles, as well. PCSK9 was positively associated with markers of glucose homeostasis and serum lipid parameters only in patients with suboptimal/poor glucoregulation. In well-controlled T1DM, plasma PCSK9 level was inversely associated with a relative proportion of sdLDL particles (p < 0.01) and this association remained significant in multivariate analysis. In T1DM patients with suboptimal/poor glycemic control, PCSK9 was positively associated with the proportion of the smallest HDL3c particles (p < 0.001), but negatively with HDL size (p < 0.05).
CONCLUSIONS
The extent of achieved metabolic control modifies the association between PCSK9 and lipoprotein subclasses in T1DM. Further investigations are needed to reveal whether the observed effects of glycemic control on PCSK9 and sdLDL levels have causal consequences on CVD risk in young patients with T1DM.
Identifiants
pubmed: 30453116
pii: S0021-9150(18)31475-8
doi: 10.1016/j.atherosclerosis.2018.11.020
pii:
doi:
Substances chimiques
Blood Glucose
0
Cholesterol, HDL
0
Cholesterol, LDL
0
Insulin
0
Lipoproteins, HDL
0
Lipoproteins, LDL
0
Cholesterol
97C5T2UQ7J
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14-20Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.