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

TY - JOUR

T1 - Diabetic and nondiabetic patients with nonalcoholic fatty liver disease have an impaired incretin effect and fasting hyperglucagonaemia

AU - Junker, A E

AU - Gluud, L

AU - Holst, J J

AU - Knop, F K

AU - Vilsbøll, T

N1 - © 2016 The Association for the Publication of the Journal of Internal Medicine.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

U2 - 10.1111/joim.12462

DO - 10.1111/joim.12462

M3 - Journal article

C2 - 26728692

SN - 0954-6820

VL - 279

SP - 485

EP - 493

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

IS - 5

ER -