Combined intake of glucose-and lipid-lowering medications further elevates plasma levels of PCSK9 in type 2 diabetes patients

Abstract

Background and aim: This study examined the status of plasma levels of protein convertase subtilisin/kexin 9 (PCSK9) in association with glucose-and lipid-lowering medications in subjects with type 2 diabetes (T2D).

Methods: This study comprised 177 diabetics and 115 non-diabetic subjects recruited from the United Arab Emirates National Diabetes Study (UAEDIAB). Clinical and biomedical data were collected by standard techniques. Plasma levels of PCSK9 were determined using ELISA.

Results: PCSK9 levels were higher in diabetics than non-diabetics (P < 0.001). Diabetics with disease duration >5 years, HbA1c > 7.0%, or male subjects, had significantly higher levels of PCSK9 than their counterparts (P < 0.05). Regression analysis revealed that HbA1c and age are predictors for PCSK9 in T2D subjects. Diabetic subjects with abnormal lipids profile on lipid-lowering medications had a higher level of PCSK9 compared to those with normal lipids profile (85.6 ± 40.5 vs. 63.7 ± 39.5 ng/ml, respectively; P < 0.01). Diabetics on combined intake of insulin and oral glucose-lowering drugs had higher levels of PCSK9 than those not taking any (86.1 ± 41.6 vs 69.7 ± 36.1 ng/ml, respectively; P < 0.05). The highest levels of PCSK9 however, were in diabetics on combined lipid- and glucose-lowering therapy when compared to those, not on any (96.2 ± 34.0 vs 66.0 ± 35.1 ng/ml, respectively; P < 0.01).

Conclusions: Age and HbA1c are the most predictors for the elevated levels of PCSK9 in Emirati T2D subjects. Combined therapy of glucose-and lipid-lowering medications further elevates plasma levels of PCSK9 in diabetic subjects.

Keywords: Diabetes mellitus; Insulin; Metformin; PCSK9; Statins.