The Associations of Total Testosterone with Nonalcoholic Fatty Liver Disease Inflammatory and Fibrotic Progression in Men with Type 2 Diabetes: A Cross-sectional Study
Objective: Men with type 2 diabetes mellitus (T2DM) are predisposed to hypogonadism. Testosterone has an impact on metabolic disorders and it may play different roles in the progression of nonalcoholic fatty liver disease (NAFLD). We aim to investigate whether total testosterone is associated with NAFLD progression in men with T2DM.
Methods: It is a cross-sectional study. A total of 1782 male participants with T2DM were enrolled from seven communities in Shanghai. Probable nonalcoholic steatohepatitis (NASH) was defined by the concurrence of NAFLD and metabolic syndrome (MetS). NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. Multinomial logistic regression and ordinal logistic regression was used to measure the association of total testosterone (independent variable) and the progression category of NAFLD (dependent variable).
Results: In male, TT quartiles were negatively associated with probable NASH (Q1 vs. Q4 OR 2.07 95%CI, 1.31-3.28, P for trend=0.001) and inflammatory progression of NAFLD with OR of 1 SD increment of ln (TT) 0.81 (95% CI 0.72-0.92, P for trend < 0.001), but positively with fibrotic progression (Q1 vs. Q4 OR 0.45, 95% CI 0.29-0.72, P for trend=0.001) with OR of 1 SD increment of ln (TT) 1.24 (95% CI 1.07-1.45). According to stratified analyses, for inflammatory progression, the interactions of age strata, duration of diabetes strata and dyslipidemia status with 1 SD increment of ln (TT) were significant (P for interaction 0.007,0.003 and 0.012 respectively); as for fibrotic progression, we found no interactions (all P for interaction ≥0.05).
Discussion/Conclusion: In this population-based study including 1782 male patients with T2DM, we found that TT of male patients was negatively associated with probable NASH and NAFLD inflammatory progression but positively with fibrotic progression. Our results indicate that in male patients with T2DM, testosterone may play significant but opposite roles in inflammatory and fibrotic progression of NAFLD. Hence, understanding androgen hormone changes during T2DM and differentiating the stages of NAFLD may help clinicians personalize treatment strategy for male NAFLD patients with T2DM.