Glucagon is associated with NAFLD inflammatory progression in type 2 diabetes, not with NAFLD fibrotic progression

Higher prevalence of progressive stages of nonalcoholic fatty liver disease (NAFLD) and hyperglucagonemia were observed in type 2 diabetes. We aim to investigate whether islet alpha cell dysfunction (evaluated by glucagon) associates with NAFLD progression in type 2 diabetic adults.

A total of 4937 diabetic participants were enrolled from seven communities in Shanghai, China. Probable nonalcoholic steatohepatitis (NASH) was defined by the presence of NAFLD and metabolic syndrome. Probable NAFLD fibrosis score was used to identify patients with different risk stratification of bridging fibrosis (stage 3) or cirrhosis (stage 4).

After adjustment for age, sex, duration of diabetes, current smoking, waist circumference, C-peptide, HbA1c, dyslipidemia, hypertension and use of incretins and SGLT2 inhibitor, glucagon quartiles were negatively associated with probable NASH (Q4 vs. Q1 OR 0.71, 95% confidence interval, 0.53-0.96, P for trend=0.010), though they were not associated with simple NAFLD (P for trend=0.176). Furthermore, glucagon was not significantly associated with fibrotic progression of liver steatosis in diabetic patients with NAFLD (P for trend=0.889).

Significant associations were observed among glucagon and inflammatory progression of NAFLD, but not with fibrotic progression. Further understanding the association between islet alpha cell and liver may lead to development of treatment strategies for NAFLD patients with type 2 diabetes.