PCSK9 LOF Variant Linked to Higher Risk of Prediabetes, Diabetes
1. PCSK9 loss-of-function genetic variant is associated with pre-diabetes and diabetes
Background- Recent meta-analysis have shown a dose-dependent effect of statins therapy on the increased incidence of new-onset diabetes. PCSK9 inhibitors are the
emerging lipid lowering therapies. PCSK9 loss-of-function (LOF) mutations have been associated with low LDL-C and cardiovascular risk but their impact on glucose
homeostasis and the risk of diabetes is still unclear. Objective- We investigated the effect of PCSK9 LOF variant on the incidence of pre-diabetes and diabetes.
YG Luna Saavedra1,2, R Dufour2, A Baass1,2
1Department of Medicine, Division of Experimental Medicine, McGill University;
2Nutrition, Metabolism and Atherosclerosis Clinic, Institut de Recherches Cliniques de Montréal (Québec,
Canada)
Higher frequency of diabetes/prediabetes in InsLEU-carriers
Genetic variation frequency in a Familial Hypercholesterolemia
cohort. (A) LDLR and (B) PCSK9 gene variations.
Lower frequency of coronary events in InsLEU-carriers.
(Coronary events: myocardial infarction, angina, PTCA/stenting and
CABG surgery)
.
Conclusions :
Funding:
FH individuals carrying the PCSK9-InsLEU genetic
variant benefit of lower risk of coronary events but,
show an increased occurrence of pre-diabetes and
diabetes. In light of these results, further investigation
is needed to better understand the potential long-
term metabolic effects of the new PCSK9-lowering
therapies and the risk of new-onset diabetes.
Fondation Leducq Transatlantic
Network of Excellence
Patients characteristics. (n) indicate the number of patients
*median (ITQ)
Glucose & Impaired fasting glucose assessment in InsLEU-
carriers.