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.

Automated summary

Diabetes mellitus (DM) is strongly associated with atherosclerotic cardiovascular disease (ASCVD), and the protein PCSK9 has been identified as a key regulator of LDL-C levels and a potential target for improving cardiovascular outcomes. Recent studies have also linked PCSK9 to glucose metabolism, and clinical trials suggest that PCSK9 inhibitors are more effective in treating patients with DM. This review summarizes the current findings on the association between PCSK9 and glucose metabolism, including the effects of PCSK9 genetic mutations, plasma PCSK9 concentrations, and glucose-lowering drugs on metabolic parameters, as well as the impact of PCSK9 inhibitors on cardiovascular outcomes in patients with DM.