Glycaemic control influences the relationship between plasma PCSK9 and LDL cholesterol in type 1 diabetes

Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of LDL cholesterol metabolism. Little is known, however, about the regulation of PCSK9 in patients with type 1 diabetes (T1D). In the present study, we aimed to determine the relationship between circulating PCSK9 and metabolic variables in T1D. Plasma PCSK9 levels were measured in 195 people with T1D (mean age 38.8 years, mean diabetes duration 17.2 years, mean glycated haemoglobin [HbA1c] 8.3%), who were free of any lipid-lowering agent. Plasma PCSK9 was positively correlated with LDL cholesterol (P = .0007), triglycerides (P = .004), apolipoprotein B (P = .005), HbA1c (P = .003), systolic (P = .003) and diastolic (P = .001) blood pressure and body mass index (0.02). In multivariate analysis, PCSK9 concentration was independently associated with HbA1c (P = .02) and LDL cholesterol (P = .03). After classifying patients according to HbA1c tertile, the correlation between PCSK9 and LDL cholesterol was only observed in the highest tertile (P = .0006; Rho = 0.43), whereas no correlation was found in the lowest and intermediate tertiles. This study suggests that good glycaemic control abolishes the positive relationship between PCSK9 and LDL cholesterol in patients with T1D; however, the underlying molecular mechanisms remain to be established.