Serum PCSK9 is not independently associated with dyslipidaemia in type 2 diabetes: a paired cross-sectional study

Dyslipidaemia is common in type 2 diabetes mellitus (T2DM) and contributes substantially to cardiovascular risk. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor turnover, yet its relationship to the lipid phenotype in T2DM remains uncertain.

To compare lipid fractions and PCSK9 concentrations between matched individuals with and without T2DM and to determine whether PCSK9 is independently associated with dyslipidaemia.

A total of 100 age- and sex-matched pairs were enrolled. After excluding pairs with incomplete or compromised lipid or PCSK9 measurements, 92 pairs were retained for the primary analysis. Missingness was primarily due to inadequate sample volume and hemolyzed specimens. Fasting total cholesterol (TC), HDL-C, LDL-C, and triglycerides (TG) were measured in mmol/L, and serum PCSK9 was quantified in native assay units. Primary analyses used within-pair differences (paired t and Wilcoxon tests) and linear mixed-effects models (outcome ~ group + (1|pair_id)). Logistic regression evaluated associations of PCSK9 and diabetes status with dyslipidaemia, defined as LDL-C ≥ 3.37 mmol/L, HDL-C < 1.03 mmol/L, or TG ≥ 1.70 mmol/L. Multiple testing was controlled by the Benjamini-Hochberg false-discovery rate and Bonferroni correction.

Compared with controls, participants with T2DM had significantly higher lipid fractions but similar PCSK9 concentrations. Mean paired differences (T2DM - Control [95% CI]) were: TC + 0.91 mmol/L (0.46 to 1.37), HDL-C + 1.11 mmol/L (0.90 to 1.32), LDL-C + 2.12 mmol/L (1.78 to 2.46), and TG + 0.59 mmol/L (0.50 to 0.68) (all p < 0.001); PCSK9 - 0.58 (-1.57 to 0.41, p = 0.25). In mixed-effects models, group effects remained significant for all lipid fractions but not for PCSK9. In logistic regression, PCSK9 was not associated with dyslipidaemia (OR 0.99, 95% CI 0.91-1.08, p = 0.81; AUC 0.51).

Among matched adults with and without T2DM, serum PCSK9 showed no independent association with dyslipidaemia despite significant elevations in TC, LDL-C, HDL-C, and TG in the diabetic group. Interpretation is limited by the lack of HbA1c and lipid-modifying medication data and by single-time sampling. These findings suggest that PCSK9 alone may have limited utility for classifying dyslipidaemia in T2DM without adjustment for metabolic and therapeutic covariates.

Not applicable.