Insight into the role of PCSK9 in glucose metabolism

Diabetes mellitus (DM) is strongly associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) was recently identified as an important regulator of circulating low-density lipoprotein-cholesterol (LDL-C) levels via degradation of the LDL receptor, proving to be a valid target to improve lipoprotein profiles and cardiovascular outcomes in patients with ASCVD. Beyond LDL receptor processing and cholesterol homeostasis, the PCSK9 protein has recently been verified to be associated with glucose metabolism. Importantly, clinical trials suggest that treatment with PCSK9 inhibitors for patients with DM is more effective. Hence, in this review, we summarize the current findings derived from experimental, preclinical, and clinical studies regarding the association between PCSK9 and glucose metabolism, including the relationship of PCSK9 genetic mutations to glucose metabolism and diabetes, the link between plasma PCSK9 concentrations and glucose metabolic parameters, the effects of glucose-lowering drugs on plasma PCSK9 levels and the impacts of PCSK9 inhibitors on cardiovascular outcomes of patients with DM. Clinically, exploring this field may improve our understanding regarding the roles of PCSK9 in glucose metabolism and may offer an in-depth interpretation of how PCSK9 inhibitors exert effects on the treatment of patients with DM.