Elevated glucagon and postprandial hyperglycemia in fatty liver indicate early glucose intolerance in metabolic dysfunction associated steatotic liver disease.

In Japan, fatty liver cases with elevated body mass index are increasing. Because of being non-malignant, these are often neglected unless accompanied by diabetes. This study investigated the risk of glucose intolerance in individuals with non-alcoholic fatty liver. We included 165 men (mean age 56.3 years; range 29-75 years) who underwent an overnight 2-day physical examination at our Health Evaluation Center. All patients underwent abdominal ultrasonography to examine fatty liver. Fasting blood glucose and 75-g glucose tolerance test (OGTT) were conducted. alanine aminotransferase (ALT) (p < 0.01) and triglyceride (p < 0.001) levels were significantly higher in the fatty liver group (FL) than in the non-fatty liver group. HbA1c, fasting blood glucose, and blood glucose level at OGTT (0 and 30 min) did not show significant differences. In the FL, OGTT was significantly elevated at 60 min(p < 0.01)and 120 min (p < 0.001), insulin level was significantly elevated at 0 and 30 min (p < 0.001), and glucagon level was significantly elevated at 0 min (p < 0.05) and 30 min (p < 0.01), with no significant differences between the groups at 60 and 120 min. This is the first study to demonstrate elevated glucagon levels after OGTT. Metabolic dysfunction-associated steatotic liver disease (MASLD) requires treatment for insulin resistance with glucagon dysregulation likely associated with its pathogenesis.