Journal
JOURNAL OF INTERNAL MEDICINE
Volume 279, Issue 5, Pages 485-493Publisher
WILEY
DOI: 10.1111/joim.12462
Keywords
glucagon; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; incretin effect; nonalcoholic fatty liver disease; type 2 diabetes
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Funding
- Novo Nordisk Foundation
- NNF Center for Basic Metabolic Research [Holst Group] Funding Source: researchfish
- Novo Nordisk Fonden [NNF16OC0020224, NNF15OC0016230, NNF12OC1015904] Funding Source: researchfish
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ObjectiveWe evaluated whether patients with histologically verified nonalcoholic fatty liver disease (NAFLD) have an impaired incretin effect and hyperglucagonaemia. MethodsFour 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. ResultsControls 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. ConclusionsPatients with NAFLD have a reduced incretin effect and fasting hyperglucagonaemia, with the latter occurring independently of glucose (in)tolerance.
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