Diabetic and nondiabetic patients with nonalcoholic fatty liver disease have an impaired incretin effect and fasting hyperglucagonaemia

J Intern Med. 2016 May;279(5):485-93. doi: 10.1111/joim.12462. Epub 2016 Jan 5.


Objective: We evaluated whether patients with histologically verified nonalcoholic fatty liver disease (NAFLD) have an impaired incretin effect and hyperglucagonaemia.

Methods: Four groups matched for age, sex and body mass index were studied: (i) 10 patients with normal glucose tolerance and NAFLD; (ii) 10 patients with type 2 diabetes and NAFLD; (iii) eight patients with type 2 diabetes and no liver disease; and (iv) 10 controls. All participants underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycaemic intravenous glucose infusion (IIGI). We determined the incretin effect by relating the beta cell secretory responses during the OGTT and IIGI. Data are presented as medians (interquartile range), and the groups were compared by using the Kruskal-Wallis test.

Results: Controls exhibited a higher incretin effect [55% (43-73%)] compared with the remaining three groups (P < 0.001): 39% (44-71%) in the nondiabetic NAFLD patients, 20% (-5-50%) in NAFLD patients with type 2 diabetes, and 2% (-8-6%) in patients with type 2 diabetes and no liver disease. We found fasting hyperglucagonaemia in NAFLD patients with [7.5 pmol L(-1) (6.8-15 pmol L(-1))] and without diabetes [7.5 pmol L(-1) (5.0-8.0 pmol L(-1))]. Fasting glucagon levels were lower but similar in patients with type 2 diabetes and no liver disease [4.5 pmol L(-1) (3.0-6.0 pmol L(-1))] and controls [3.4 pmol L(-1) (1.8-6.0 pmol L(-1) )]. All groups had similar glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide responses.

Conclusions: Patients with NAFLD have a reduced incretin effect and fasting hyperglucagonaemia, with the latter occurring independently of glucose (in)tolerance.

Keywords: glucagon; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; incretin effect; nonalcoholic fatty liver disease; type 2 diabetes.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • C-Reactive Protein / metabolism
  • Diabetes Mellitus, Type 2 / complications*
  • Fasting / blood
  • Female
  • Gastric Inhibitory Polypeptide / metabolism
  • Glucagon / blood*
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose Intolerance / complications
  • Glucose Intolerance / diet therapy
  • Humans
  • Incretins / metabolism*
  • Insulin / metabolism
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / complications*


  • Blood Glucose
  • Incretins
  • Insulin
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • C-Reactive Protein
  • Glucagon