Nonalcoholic Fatty Liver Disease is Associated with Increased Carotid Intima-Media Thickness in Type 1 Diabetic Patients

Nonalcoholic fatty liver disease (NAFLD) has emerged as a growing public health problem worldwide. In the last decade, it has become apparent that the clinical burden of NAFLD is not restricted to liver-related morbidity or mortality, and the majority of deaths in NAFLD patients are related to cardiovascular disease (CVD) and cancer. These findings have fuelled concerns that NAFLD may be a new and added risk factor for extrahepatic diseases such as CVD. A growing body of evidence suggests that NAFLD is associated with an increased risk of incident CVD events both in patients without diabetes and in those with type 2 diabetes (T2DM)1,2,3. However, very few data are available regarding the prevalence of NAFLD and its association with the CVD in type 1 diabetes (T1DM). Retrospective and prospective studies provide evidence of a strong association between NAFLD and the subclinical manifestations of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function, and coronary calcification)4,5,6,7. Measurement of carotid intima-media thickness (C-IMT) and plaque burden by ultrasound is a well-validated and widely accepted screening approach to the prediction of CVD in asymptomatic subjects8. Importantly, the severity of the histological features of NAFLD appear to be independently correlated with increasing C-IMT9. Several cross-sectional studies10,11,12,13 have shown that NAFLD is strongly associated with increased C-IMT and increased coronary artery calcium scores in nondiabetic patients and in those with T2DM, although not all studies have agreed with these findings14,15. Moreover, studies have suggested that preclinical CVD (such as C-IMT, plaque, and endothelial dysfunction) are seen more frequently and to a greater extent in patients with T1DM, even at an early age. Some data suggest that its presence may predict CVD events. However, no published data are available regarding the association between NAFLD and C-IMT as a marker of subclinical atherosclerosis or subclinical CVD in T1DM. It is important for both physicians and patients to be aware of increased CVD risk as a potential extrahepatic association of NAFLD in T1DM, as many of the tools used for screening are readily available in clinical practice (i.e., intravascular ultrasound or virtual histology). If disease is identified early, it should be managed appropriately with standard medical therapies. Therefore, the objective of this study was to investigate whether there is a difference in carotid atherosclerotic burden as a marker of subclinical CVD according to the presence of NAFLD in a large cohort of patients with T1DM and, if so, to evaluate whether NAFLD is related to C-IMT, independent of traditional CVD risk factors and metabolic syndrome.