Impact of diabetes on subclinical atherosclerosis and major cardiovascular events in individuals with and without non-alcoholic fatty liver disease

Aims: To investigate the impact of diabetes on subclinical atherosclerosis and cardiovascular disease (CVD) in individuals with and without non-alcoholic fatty liver disease (NAFLD). Methods: The prospective cohort study included 8451 Chinese adults free of baseline CVD in 2010. NAFLD was diagnosed based on hepatic ultrasonography. Fibrosis-4 index as a non-invasive marker was used to evaluate the degree of fibrosis. Subclinical atherosclerosis was evaluated by carotid intima-media thickness, brachial-ankle pulse wave velocity, ankle-brachial index, and carotid plaque. At follow-up during 2014–2016, the composite of incident fatal or nonfatal CVD were ascertained. Results: Of the 8451 participants, 2557 (30.3%) had NAFLD at baseline. Diabetes was associated with arterial stiffness and carotid plaque in participants with NAFLD (P < 0.001). Similar associations were observed in participants without NAFLD. During a mean 4.6 years of follow-up, 432 incident CVD events occurred. The multivariable-adjusted hazard ratio (HR) for CVD events associated with diabetes was 1.27 (95% CI 0.90–1.81) in participants with NAFLD and 1.73 (95% CI 1.32–2.26) in those without NAFLD (P for interaction = 0.21). Among participants with NAFLD who had pre-existing diabetes, those with ≥5 years of diabetes duration had an adjusted HR of 2.02 (95% CI 1.12–3.62) for CVD as compared to those with <2 years of duration. When categorizing participants with NAFLD by fibrosis severity, diabetes conferred an increased risk of CVD in those with potential advanced fibrosis. Conclusions: Among participants with NAFLD, diabetes was associated with prevalent atherosclerosis, and a long duration of diabetes was associated with an increased risk of developing CVD. The effects of diabetes on cardiovascular outcomes did not appreciably differ by NAFLD status.