NAFLD in type 2 diabetes mellitus: Still many challenging questions

Epidemiologic data consistently show that in patients with type 2 diabetes (T2DM) the prevalence of non-alcoholic fatty liver disease (NAFLD), including advanced fibrosis, is double compared to the general population, and it associates with high risk of liver-related morbidity (advanced fibrosis, hepatocellular carcinoma) and mortality, but also with other systemic consequences, such as cardiovascular (CV) disease, chronic kidney disease, and overall mortality. There are still many answers that need to be clarified regarding NAFLD in T2DM, including deciphering the complex pathogenetic mechanisms, the intertwined relationships with the extrahepatic organs and tissues (mainly heart, kidneys, adipose tissue, gut), the prognostic value of NAFLD for CV risk stratification, and more importantly, what would be the most appropriate screening algorithm, diagnostic method and therapeutic approach. We advocate here for proactive action, in order to identify NAFLD in a timely manner, and suggest a simple algorithm to be used in clinical practice, based on risk stratification and on experts' opinions. We discuss the current therapeutic options for NAFLD in T2DM, for which a multifactorial approach is needed, that concomitantly addresses the liver and the cardio-reno-metabolic disturbances.