Postprandial hyperinsulinemia is universal in non-diabetic patients with nonalcoholic fatty liver disease

Despite strong associations between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), it is unclear which patients need oral glucose tolerance testing (OGTT). Relationships between hyperglycemia, postprandial hyperinsulinemia and NAFLD severity also need clarification.

Among 111 consecutive NAFLD patients, 35 had established T2D; 70 of the remaining 76 underwent 75G OGTT with fasting, 60 and 120 min insulin. Hepatic fibrotic severity was estimated by NAFLD fibrosis score and evidence of cirrhosis.

Twenty-four (33%) showed abnormal glucose tolerance: seven T2D, 17 impaired glucose tolerance (IGT). NAFLD patients with newly diagnosed T2D or IGT were (mean) 9 years older and more likely female (54% vs 30%). Fasting hyperglycemia (5.6-6.9 mmol/L) had limited sensitivity (46%) but high specificity (89%) for identifying patients with IGT/T2D; positive and negative predictive values were 69% and 76%. Postprandial hyperinsulinemia (120 min) was evident in all non-diabetic NAFLD cases, and values were higher (151 ± 87 vs 82 ± 53 mU/L, P = 0.001) in those with abnormal OGTT. Patients with established diabetes were more likely to have cirrhosis (40%) than those with IGT (12%) or normal glucose tolerance (4%).

All NAFLD patients have postprandial hyperinsulinemia, and OGTT reveals a high frequency of previously unsuspected IGT or T2D. Such testing would identify individuals who may benefit from early intervention to improve insulin sensitivity and prevent diabetes and progression to cirrhosis.