Banting memorial lecture 2022: 'Type 2 diabetes and nonalcoholic fatty liver disease: Partners in crime'

Abstract

Nonalcoholic fatty liver disease (NAFLD) was first described in the 1980s, but in the 21st century, NAFLD has become a very common condition. The explanation for this relatively recent problem is in large part due to the recent epidemic of obesity and type 2 diabetes (T2DM) increasing the risk of NAFLD. NAFLD is a silent condition that may not become manifest until severe liver damage (fibrosis or cirrhosis) has occurred. Consequently, NAFLD and its complications often remain undiagnosed. Research evidence shows that NAFLD is extremely common and some estimates suggest that it occurs in up to 70% of people with T2DM. In the last 5 years, it has become evident that NAFLD not only increases the risk of cirrhosis, primary liver cancer and end-stage liver disease, but NAFLD is also an important multisystem disease that has major implications beyond the liver. NAFLD increases the risk of incident T2DM, cardiovascular disease, chronic kidney disease and certain extra-hepatic cancers, and NAFLD and T2DM form part of a vicious spiral of worsening diseases, where one condition affects the other and vice versa. Diabetes markedly increases the risk of liver fibrosis and liver fibrosis is the most important risk factor for hepatocellular carcinoma. It is now possible to diagnose liver fibrosis with non-invasive tools and therefore it is important to have clear care pathways for the management of NAFLD in patients with T2DM. This review summarises key recent research that was discussed as part of the Banting lecture at the annual scientific conference in 2022.

Keywords: GLP-1 receptor agonists; insulin resistance; liver fibrosis; nonalcoholic fatty liver disease; pioglitazone; type 2 diabetes.

FIGURE 1

illustrates the vicious cycle that exists when NAFLD and type 2 co‐exist. NAFLD increases the risk of developing T2DM and when T2DM occurs, T2DM increases the risk of developing liver fibrosis. The figure also illustrates the relationship between both T2DM and NAFLD and the risk of developing CVD. Increasing evidence suggests that both pioglitazone and GLP‐1RAs have beneficial effects on T2DM, NAFLD, and CVD as illustrated by the negative signs in the figure. GLP‐1RAs induce weight loss, and there is also a good case for dual therapy with GLP‐1RAs and pioglitazone in order to attenuate the risk of any weight gain with pioglitazone.

FIGURE 2

illustrates the various steps involved, (and that need to be tackled), between recognising that NAFLD is creating a problem and public health burden within society, and effecting change with the development of a health care strategy for NAFLD. (i to vi) illustrate the various steps involved in identifying NAFLD as a public health burden and establishing a strategy and policies for tackling NAFLD in society.