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

Atherosclerosis. 2020 Jan;293:49-56. doi: 10.1016/j.atherosclerosis.2019.11.027. Epub 2019 Nov 28.


Background and aims: PCSK9 is an endogenous inhibitor of the 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 = 1751; 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 multivariable 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.

Keywords: New onset diabetes; PCSK9; PCSK9 inhibition; Type 2 diabetes.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Brazil / epidemiology
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Proprotein Convertase 9 / blood*
  • Prospective Studies
  • Risk Factors
  • Time Factors


  • Biomarkers
  • PCSK9 protein, human
  • Proprotein Convertase 9