Circulating PCSK9 levels are not associated with the conversion to type 2 diabetes

Autor: Brice Nativel, Aurélie Thedrez, Stéphane Ramin-Mangata, Paulo A. Lotufo, Matthieu Wargny, Gilles Lambert, Valentin Blanchard, Raul D. Santos, Cédric Le May, Isabela M. Benseñor, Bertrand Cariou, Matthieu Pichelin
Přispěvatelé: unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Time Factors
Enzyme-Linked Immunosorbent Assay
Type 2 diabetes
Nod
030204 cardiovascular system & hematology
PCSK9
03 medical and health sciences
0302 clinical medicine
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Risk Factors
Internal medicine
new onset diabetes
Mendelian randomization
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Humans
Medicine
Glucose homeostasis
Prospective Studies
Prediabetes
business.industry
Proportional hazards model
Incidence
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Middle Aged
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
medicine.disease
PCSK9 inhibition
3. Good health
030104 developmental biology
Endocrinology
Diabetes Mellitus
Type 2
LDL receptor
Disease Progression
Female
type 2 diabetes
Proprotein Convertase 9
Cardiology and Cardiovascular Medicine
business
Biomarkers
Brazil
Follow-Up Studies
Zdroj: Atherosclerosis
Atherosclerosis, Elsevier, 2020, 293, pp.49-56. ⟨10.1016/j.atherosclerosis.2019.11.027⟩
ISSN: 0021-9150
DOI: 10.1016/j.atherosclerosis.2019.11.027⟩
Popis: International audience; Total word count (including tables and figure legends): 3927 Number of tables and figures : 4 2 ABSTRACT (Word count 250) Background and aims-PCSK9 is an endogenous inhibitor of LDL receptor pathway. Recently, Mendelian randomization studies have raised a doubt about the diabetogenic risk of PCSK9 inhibitors. Here, we assessed the relationship between plasma PCSK9 levels and the risk of new onset diabetes (NOD). Methods-Fasting plasma PCSK9 levels were measured at baseline by ELISA in subjects without lipid lowering treatment in IT-DIAB (n=233 patients with prediabetes, follow-up 5 years) and ELSA-Brasil (n=1,751; 27.5% with prediabetes, follow-up 4 years) prospective cohorts. The primary outcome in both studies was the incidence of NOD. The association of NOD with plasma PCSK9 levels was studied using multivariate Cox models. Results-Plasma PCSK9 levels were not significantly associated with NOD in IT-DIAB (HR (+1SD) 0.96, CI95% [0.76; 1.21]) and ELSA-Brasil (OR (+1SD) 1.13 [0.89; 1.42]). In ELSA-Brasil, a significant positive association between PCSK9 and worsening of glucose homeostasis, including the progression from normoglycemia to prediabetes, was found (OR (+1SD) 1.17 [1.04; 1.30], P=0.0074). Plasma PCSK9 concentration was also positively associated with the change in fasting plasma glucose between the first and second visit in ELSA-Brasil (β = 0.053, CI95% [0.006; 0.10], P=0.026). Plasma PCSK9 levels positively correlated with total cholesterol in IT-DIAB and ELSA-Brasil, but not with glucose homeostasis parameters, except for a positive correlation with HOMA-IR in ELSA-Brasil. Conclusions-Plasma PCSK9 levels were not significantly associated with NOD risk in longitudinal analyses. These data suggest that inhibition of the PCSK9 extra-cellular pathway should not be deleterious for glucose homeostasis.
Databáze: OpenAIRE
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