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.