title: Assessment of CYP1A2 enzyme activity in relation to type-2 diabetes and habitual caffeine intake.
abstract: BACKGROUND
  Coffee consumption is a known inducer of cytochrome P450 1A2 (CYP1A2) enzyme activity. We recently observed that a group of type-2 diabetes patients consumed more caffeine (coffee) on a daily basis than non-type-2 diabetes controls. Here, we investigated whether type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls.
  
  
  METHODS
  To estimate CYP1A2 enzyme activity, an established marker of caffeine metabolism, we quantified the paraxanthine/caffeine concentration ratio in saliva in 57 type-2 diabetes and 146 non-type-2 diabetes participants in a case-control field study. All participants completed validated questionnaires regarding demographic status, health and habitual caffeine intake, and were genotyped for the functional -163C > A polymorphism of theCYP1A2gene.
  
  
  RESULTS
  In the diabetes group, we found a larger proportion of participants with the highly inducibleCYP1A2genotype. Furthermore, the paraxanthine/caffeine ratio, time-corrected to mitigate the impact of different saliva sampling times with respect to the last caffeine intake, was higher than in the control group. Participants who reported habitually consuming more caffeine than the population average showed higher CYP1A2 activity than participants with lower than average caffeine consumption. Multiple regression analyses revealed that higher caffeine intake was potentially an important mediator of higher CYP1A2 activity.
  
  
  CONCLUSIONS
  Estimated CYP1A2 enzyme activity, and thus speed of caffeine metabolism, was higher in our type-2 diabetes group; this was possibly due to higher intake of caffeine, a known inducer of CYP1A2 enzyme activity. Given the fairly small sample sizes, the results need to be considered as preliminary and require validation in larger populations.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland ; Zürich Center of interdisciplinary Sleep Research, University of Zürich, Zürich, Switzerland ; Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
authors.forename: Emily
authors.initials: E
authors.lastname: Urry
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jetter
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland ; Zürich Center of interdisciplinary Sleep Research, University of Zürich, Zürich, Switzerland.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Landolt
keywords: Caffeine; HPLC; Paraxanthine; Phenotyping