title: Postprandial hyperinsulinemia is universal in non-diabetic patients with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Gastroenterology and Hepatology Unit, the Australian National University Medical School, Canberra, Australian Capital Territory, Australia.
authors.forename: Jayani
authors.initials: J
authors.lastname: Manchanayake
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Chitturi
authors.forename: Christopher
authors.initials: C
authors.lastname: Nolan
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Farrell
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D020958:Australian Capital Territory; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D018450:Disease Progression; D005234:Fatty Liver / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D019518:Postprandial Period; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007328:Insulin