Nonalcoholic Fatty liver: a possible new target for type 2 diabetes prevention and treatment

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed.

Figure 1

The pathogenetic link between non-alcoholic fatty liver disease (NAFLD), diabetes, CVD and CKD. Visceral adipose tissue releases inflammatory cytokines that induce liver damage. In turn, fatty liver is not only a target of these cytokines, but also the source of several proinflammatory, proatherogenic and nephrotoxic factors that may play a role in the development and progression of both cardiovascular disease (CVD) and chronic kidney disease (CKD). Moreover, NAFLD promotes T2DM development and enhances cardiovascular risk through the contribution to hepatic/systemic insulin resistance and atherogenic dyslipidemia. Additionally, NAFLD may contribute to the pathogenesis of T2DM through the release of some liver-secreted proteins with diabetogenic properties, such as fetuin-A, fibroblast growth factor-21, and retinol binding protein-4. On the other side, T2DM favors NAFLD progression.