Evaluation of important human CYP450 isoforms and P-glycoprotein
phenotype changes and genotype in type 2 diabetic patients, before and
after treatment, by using Geneva cocktail
Abstract
The present study evaluates the influence of type 2 diabetes (T2D) on
important CYP450 isoforms and P-glycoprotein (P-gp) transporter
activities before and 3 months after intensifying treatment regimen of
40 patients. Results have been compared with 21 non-T2D healthy
participants (control group). CYPs and P-gp activities were assessed
after administration of Geneva cocktail. Mean metabolic ratios (MR) for
CYP2B6 (1.81±0.93 vs. 2.68±0.87), CYP2C19 (0.420 ± 0.360 vs. 0.687 ±
0.558), and CYP3A4/5 (0.487 ± 0.226 vs. 0.633 ± 0.254) significantly
decreased in T2D subjects compared to control group (p<0.05).
CYP2C9 (0.089±0.037 vs. 0.069±0.017) activities slightly increased in
diabetic subjects and no difference was observed for CYP1A2 (0.154±0.085
vs. 0.136±0.065), CYP2D6 (1.17 ± 0.56 vs. 1.24 ± 0.83) and P-gp
activities in comparison with control group. Three months after
intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and
CYP3A4/5 (0.592 ± 0.268) have shown a significant improvement and were
not statistically different compared to 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 our analyses. Our results indicate that low chronic
inflammatory status associated with T2D modulates CYP450 activities in
an isoform specific manner.