Non-alcoholic fatty liver disease and diabetes: from physiopathological interplay to diagnosis and treatment

Abstract

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2 diabetes are at a particularly high risk for developing the progressive forms of NAFLD, non-alcoholic steatohepatitis and associated advanced liver fibrosis. Moreover, diabetes is an independent risk factor for NAFLD progression, and for hepatocellular carcinoma development and liver-related mortality in prospective studies. Notwithstanding, patients with NAFLD have an elevated prevalence of prediabetes. Recent studies have shown that NAFLD presence predicts the development of type 2 diabetes. Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients. The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods, although histopathological evaluation is still considered the gold standard diagnostic method. An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking. We sought to outline the published data including epidemiology, pathogenesis, diagnosis and treatment of NAFLD in diabetic patients, in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

Keywords: Diabetes mellitus; Diagnosis; Non-alcoholic fatty liver disease; Pathogenesis; Treatment.

Figure 1

Pivotal role of insulin resistance in non-alcoholic fatty liver disease pathophysiology. ↓: Decrease; ↑: Increase. FFA: Free fatty acids; DM: Diabetes mellitus; NAFLD: Non-alcoholic fatty liver disease.

Figure 2

Main physiopathological mechanisms influencing non-alcoholic fatty liver disease. Progression to non-alcoholic steatohepatitis and fibrosis. ↓: Decrease; ↑: Increase. NASH: Non-alcoholic steatohepatitis; FFA: Free fatty acids.