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.

Atherogenic index of plasma is an independent predictor of metabolic-associated fatty liver disease in patients with type 2 diabetes

“…The relationship between retinopathy and MAFLD, however, remains conflicting with limited available studies [ 24 ]. Regarding macrovascular complications, cardiovascular disease remains the most common cause of death among patients with MAFLD, and previous studies have demonstrated that patients with MAFLD are at a higher risk for CVD events, despite adjusting for relating confounders [ 24 ]. On the other hand, in patients with T2D, MAFLD progresses to cirrhosis at a much faster pace [ 29 ].…”

“…Previous research has illustrated a negative correlation between anti-lipid therapy and AIP level [ 24 ]. Therefore, compared to the aforementioned studies [ 10 , 11 , 13 ], we went one step further and included anti-lipid therapy as a confounding factor in our analysis and still managed to demonstrate a high odds ratio.…”

“…Prompt diagnosis of MAFLD in patients with T2D, using a biomarker like AIP, is critical both due to the adverse outcomes that late diagnosis harbors, and because of the emerging pharmacotherapeutic interventions targeting MAFLD [24,25]. Several observational studies have described an independent association between microvascular complications, such as chronic kidney disease and distal/autonomic neuropathy, and MAFLD [26][27][28].…”

Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank

“…Aside from the direct proarrhythmic effects of adipose secretome, chronic obesity confers arrhythmic risks via systemic metabolic complications, such as non-alcoholic fatty liver disease (NAFLD) ( 21 , 22 ). NAFLD has been linked to higher rates of adverse cardiovascular outcomes ( 23 ) that include greater risks of atrial fibrillation ( 24 – 26 ), QTc prolongation ( 27 , 28 ), and VA ( 29 , 30 ).…”

“…NAFLD has been linked to higher rates of adverse cardiovascular outcomes ( 23 ) that include greater risks of atrial fibrillation ( 24 – 26 ), QTc prolongation ( 27 , 28 ), and VA ( 29 , 30 ). Insulin resistance and dysregulated lipid metabolism resulting in release of pro-inflammatory, -fibrotic and -oxidising hepatic mediators may underpin these observations ( 22 , 31 , 32 ). Furthermore, NAFLD favours epicardial fat accumulation resulting in cardiac lipotoxicity, fatty infiltration, fibrosis, and yet more secretion of inflammatory mediators.…”