Editorial
Copyright ©The Author(s) 2017.
World J Diabetes. Jul 15, 2017; 8(7): 311-316
Published online Jul 15, 2017. doi: 10.4239/wjd.v8.i7.311
Table 1 Studies that examined the association of proprotein convertase subtilisin/kexin type 9 with carbohydrate metabolism
Ref.TypeMain findings
Studies pointing to a positive effect of PCSK9 on carbohydrate metabolism
Mbikay et al[14]Experimental (mice)PCSK9-null male mice over 4 mo of age carried more LDLR and less insulin in their pancreas; islets exhibited signs of malformation, apoptosis and inflammation
Awan et al[11]Genetic studyCarriage of the loss-of-function PCSK9 p.R46L mutation was associated with insulin resistance in subjects with apolipoprotein E3/E2 genotype
Studies pointing to a negative effect of PCSK9 on carbohydrate metabolism
Langhi et al[13]Experimental (mice)PCSK9 deficiency does not alter insulin secretion and glucose tolerance
Baass et al[18]Clinical study (children)Significant correlation of PCSK9 levels with glucose, insulin and HOMA-IR levels; an increase in PCSK9 levels by 1%-2% was associated with 10% higher fasting insulin levels in both sexes
Arsenault et al[21]Clinical study (abdominally obese men)PCSK9 levels are associated with dyslipidemia and with increased HOMA-IR
Studies pointing to a neutral effect of PCSK9 on carbohydrate metabolism
Bonnefond et al[12]Genetic studyThe p.R46L mutation is not associated with markers of glucose homeostasis; p.R46L carriers did not experience an increased risk of new-onset diabetes mellitus
Colhoun et al[22]Analysis of 10 phase 3 clinical trials with alirocumab (3448 non-diabetic individuals)Hazard ratio for diabetes-related treatment adverse effects 0.64 (95%CI: 0.36-1.14) in alirocumab-treated patients vs placebo-treated and 0.55 (95%CI: 0.22-1.41) vs ezetimibe-treated patients
Blom et al[23]Post hoc analysis of the DESCARTES trial (evolocumab)No changes in parameters of carbohydrate metabolism in patients with pre-existing dysglycemia or metabolic syndrome
Ongoing trials that may better delineate the role of PCSK9 inhibition on carbohydrate metabolism
Fourier trial (ClinicalTrials.gov Identifier: NCT01764633)Ongoing trialPrimary hypothesis is that additional LDL-c lowering with evolocumab decreases the risk of cardiovascular events in subjects with clinically evident cardiovascular disease
Odyssey trial (ClinicalTrials.gov Identifier: NCT01663402)Ongoing trialPrimary hypothesis is that additional LDL-c lowering with alirocumab decreases the risk of cardiovascular events in patients who have experienced an acute coronary syndrome event 4 to 52 wk prior to randomization