Statin therapy in type 2 diabetes mellitus is associated with increased circulating PCSK9 levels independent from liver disease

Background:

Statin therapy is common in type 2 diabetes mellitus (T2DM) to reduce LDL-cholesterol. Effects on circulating PCSK9 levels considering fatty liver disease have not been evaluated yet.

Patients/methods:

EDTA plasma of 125 T2DM patients receiving statin therapy (STATIN+) vs. 103 T2DM patients not receiving statin therapy were analyzed by ELISA recognizing free and LDL receptor-bound PCSK9. Statistical analysis was done using GraphPad Prism 6.05, values are given as mean ± SD.

Results:

STATIN+ patients were significantly older (61.1 ± 11.4 vs. 57.5 ± 14.0 years; p = 0.035), but presented comparable values for HbA1c (9.0 ± 2.0 vs. 9.1 ± 2.2%), triglycerides (295.4 ± 30.6 vs. 287.4 ± 218.0 mg/dl), total cholesterol 190.5 ± 60.1 vs. 202.0 ± 46.6 mg/dl) and HDL cholesterol (43.1 ± 12.8 vs. 42.8 ± 15.3 mg/dl; p > 0.05 for all). Patients did not differ regarding liver function parameters ASAT 39.6 ± 25.5 vs. 45.9 ± 31.2 U/l, ALAT 49.8 ± 37.8 vs. 54.0 ± 36.1 U/l; p > 0.05 for all). LDL cholesterol values were lower in STATIN+ patients (106.0 ± 40.1 vs. 120.8 ± 39.8 mg/dl; p = 0.0088). PCSK9 levels were elevated in STATIN+ patients (320.9 ± 76.2 vs. 233.0 ± 72.2 ng/ml; p < 0.0001).

By separating patients into subgroups with underlying liver disease (ALAT> 35U/L in women, ALAT> 50U/L in men) no correlation between PCSK-9 levels and ALAT was detected. PCSK-9 values were independent from elevated ALAT values on a comparable level. Only in patients with elevated ALAT levels receiving statin therapy a weak correlation between PCSK-9 levels and total cholesterol (0.375; p < 0.05) as well as triglycerides (0.326; p < 0.05) was detected.

Conclusion:

Statin therapy induced higher circulating levels of PCSK-9 which might be a response to increased LDL-receptor occurrence following statin therapy independently from fatty liver disease. This hypothesis warrants further clarification.