Non-Alcoholic Fatty Liver Disease and Risk of Macro- and Microvascular Complications in Patients with Type 2 Diabetes

Abstract

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. To date, NAFLD is the most frequent chronic liver disease seen day by day in clinical practice across most high-income countries, affecting nearly 25-30% of adults in the general population and up to 70% of patients with T2DM. Over the last few decades, it clearly emerged that NAFLD is a "multisystemic disease" and that the leading cause of death among patients with NAFLD is cardiovascular disease (CVD). Indeed, several observational studies and some meta-analyses have documented that NAFLD, especially its advanced forms, is strongly associated with fatal and non-fatal cardiovascular events, as well as with specific cardiac complications, including sub-clinical myocardial alteration and dysfunction, heart valve diseases and cardiac arrhythmias. Importantly, across various studies, these associations remained significant after adjustment for established cardiovascular risk factors and other confounders. Additionally, several observational studies and some meta-analyses have also reported that NAFLD is independently associated with specific microvascular conditions, such as chronic kidney disease and distal or autonomic neuropathy. Conversely, data regarding a potential association between NAFLD and retinopathy are scarce and often conflicting. This narrative review will describe the current evidence about the association between NAFLD and the risk of macro- and microvascular manifestations of CVD, especially in patients with T2DM. We will also briefly discuss the biological mechanisms underpinning the association between NAFLD and its advanced forms and macro- and microvascular CVD.

Keywords: CVD; NAFLD; NASH; cardiovascular complications; cardiovascular disease; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; type 2 diabetes.

Figure 1

Progression of non-alcoholic fatty liver disease (NAFLD). The stages of NAFLD development classically are simple steatosis, non-alcoholic steatohepatitis (NASH) and cirrhosis.

Figure 2

Macro- and microvascular manifestations of cardiovascular disease (CVD) linked to NAFLD and its advanced forms. Several observational studies and meta-analyses have clearly reported that NAFLD, mainly in its advanced forms, is strongly associated with an increased risk of sub-clinical myocardial remodelling and dysfunction, heart valve diseases, cardiac arrhythmias, chronic kidney disease, and distal or autonomic neuropathy. See text for details.