Abstract
The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P-glycoprotein (Pgp) transporter activities before and 3 months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non-T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail. The mean metabolic ratios (MR) for CYP2B6 (1.81 ±0.93 versus 2.68 ±0.87), CYP2C19 (0.420 ±0.360 versus 0.687 ±0.558) and CYP3A4/5 (0.487 ±0.226 versus 0.633 ±0.254) significantly decreased in T2D patients compared to the control group (p < 0.05). CYP2C9 (0.089 ±0.037 versus 0.069 ±0.017) activities slightly increased in diabetic patients, and no difference was observed regarding CYP1A2 (0.154 ±0.085 versus 0.136 ±0.065), CYP2D6 (1.17 ±0.56 versus 1.24 ±0.83), and Pgp activities in comparison to the control group. Three months after the intensifying treatment regimen, MRs of CYP2C9 (0.080 ±0.030) and CYP3A4/5 (0.592 ±0.268) improved significantly and were not statistically different compared to the control group (P > 0.05). Several covariables, such as inflammatory markers (IL-1β and IL-6), genotypes, diabetes and demographic-related factors, were considered in the analyses. The results indicate that chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform-specific manner.
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