Projects per year
Methods Associations of PCSK9 variants with LDL-C, fasting blood glucose, HbA1c, fasting insulin, weight and T2DM risk, available for over 550,000 individuals and 51,623 T2DM cases, were estimated using a standardised analysis plan, meta-analyses and weighted gene-centric scores (GS).
Findings Combined analysis of four independent PCSK9 variants scaled to 1 mmol/L lower LDL-C resulted in the following associations: fasting glucose (0·09 mmol/L; 95%CI 0·02; 0·15), HbA1c (0·03%; 95%CI -0·01; 0·08), fasting insulin (0·00% 95%CI -0·06; 0·07), body weight (1·03 kg; 95%CI 0·24; 1·82), waist-to-hip ratio (0·006; 95%CI 0·003; 0·010), body mass index (0·11 kg/m2; 95%CI -0·09; 0·30), and an odds ratio of 1·29 for T2DM (95%CI 1·11; 1·50).
Interpretation PCSK9 variants associated with lower LDL-C were also associated with higher levels of glucose, weight, waist-to-hip ratio and increased T2DM risk. Trials of PCSK9 inhibitor drugs should carefully evaluate these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment as previously done for statins.
- Diabetes Mellitus
- Genetic Association Studies
- Mendelian randomisation
- PCSK9 inhibition