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

Background and Aims: 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. Methods: 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. Results: 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%). Conclusions: 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.