Understanding the NAFLD, Diabetes Connections

Understanding the link between nonalcoholic fatty liver disease (NAFLD) and diabetes may help to better treat and prevent NAFLD, according to the authors of a recent review article.

Norbert Stefan

Kenneth Cusi

Norbert Stefan, M.D., Ph.D., of the Hospital of the University of Tubingeen in Germany and Kenneth Cusi, M.D., professor of medicine and chief of the Division of Endocrinology, Diabetes and Metabolism at the University of Florida address the major mechanisms that are involved in the pathogenesis of NAFLD and type 2 diabetes in their review article published in The Lancet Diabetes & Endocrinology article,

More 25% of adults and between 3% and 10% of children globally have NAFLD, Stefan and Cusi note. The numbers increase to about 60% and 40% in adults and children with obesity, diabetes or both.

“These numbers are alarming, because NAFLD, and more so nonalcoholic steatohepatitis (NASH) and NAFLD-associated hepatic fibrosis, increase the risk of advanced liver diseases (e.g. hepatic cirrhosis, hepatic cancer) and cardiometabolic diseases (e.g. cardiovascular disease, Type 2 diabetes),” according to a news release about the review article issued by the German Center for Diabetes Research,

Stefan and Cusi identify increased consumption of energy-dense food and fructose as among the important risk factors for NAFLD. They also discuss genetically-determined visceral fatness and impaired capacity of fat deposition in the lower part of the body as important drivers of the conditions.

“The interplay of fatty liver and diabetes, involving subclinical inflammation, insulin resistance, increased glucose levels, dysregulated liver-derived proteins (hepatokines), dyslipidemia and hypercoagulation of the blood, amplifies the impact both diseases on each other, as well as of an unhealthy lifestyle and genetic risk on the development of other non-communicable diseases, such as cancer and cardiovascular disease,” the news release from German Center for Diabetes Research said.

The same mechanisms — subclinical inflammation, high glucose levels and insulin resistance — also increase the risk of individuals getting severe cases of COVID-19, the researchers noted.

“Metabolic pathways are key in understanding why NAFLD develops and how it impacts on other diseases,” Stefan said. "Therefore, it is now time to use a holistic approach to study the pathogenesis of NAFLD.”

Modifiable risk factors, such as poor nutrition in early and later stages of life, and metabolic risks — including high glucose and insulin levels — need to be identified early on and treated, the researchers say.

Nonmodifiable risk factors, such as genetically-determined fatty liver and unhealthy storage of fat and ageing-associated redistribution of fat and decrease in muscle mass, are also important to consider, they argue.

In the future, applying these concepts will enable a personalized risk prognosis and individualized treatment of NAFLD, according to Stefan and Cusi. “In addition, researchers will be able to specifically develop lifestyle modification programs and drugs for the respective subtypes based on the various aspects of this disease,” the German Center for Diabetes Research noted.