Liver enzymes as mediators of association between obesity and diabetes: the Guangzhou Biobank Cohort Study

Abstract Purpose To assess the proportion of the association between obesity and diabetes mediated by liver enzymes such as gamma-glutamyltransferase (GGT), alanine transaminase (ALT) and aspartate transaminase (AST). Methods Mediation analysis was used with adjustment for age, education, physical activity, smoking and alcohol use. Results 9,748 participants from Phase 3 of the Guangzhou Biobank Cohort Study were recruited in 2006-2008. For women, the association of BMI and WC with glucose was partially mediated by GGT, 30% (95% confidence interval 23% to 40%) and 28% (23% to 34%), and by ALT, 15% (14% to 25%) and 14% (10% to 18%), respectively; for men, .the proportion mediated by GGT was 16% (9% to 26%) and 23% (12% to 36%) respectively, and by ALT 12% (4% to 22%) for BMI and for WC. The association of BMI and WC with glucose was not mediated by AST for women or men. Additionally considering of mediation by lipids did not change the mediation by GGT and ALT. Conclusion The effect of obesity on diabetes is partly mediated by GGT and ALT but not AST. There is no evidence of the mediation effect by lipids. Our results may provide opportunities to identify new targets for diabetes interventions. (200 words)