Anders E Junker1,2, Lise L Gluud3, Jens J Holst1, Filip K Knop1,2, Tina Vilsbøll1. 1. Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. 2. NNF Center for Basic Metabolic Research, Department of Biomedical Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 3. Department of Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
Abstract
BACKGROUND AND AIM: The impaired glucose tolerance in cirrhosis is poorly understood. We evaluated the influence of gastrointestinal-mediated glucose disposal and incretin effect in patients with cirrhosis. METHODS: Non-diabetic patients with Child-Pugh A or B cirrhosis (n = 10) and matched healthy controls (n = 10) underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion. We presented data as median ± interquartile range and compared groups using non-parametric analysis of variance. RESULTS: Patients with cirrhosis were glucose intolerant compared with healthy controls (4-h OGTTAUC : 609 ± 458 vs 180 ± 155 min × mmol/L; P = 0.005), insulin resistant (homeostatic model assessment for insulin resistance: 3.7 ± 4.9 vs 2.6 ± 1.4; P = 0.014) and had fasting hyperglucagonemia (8 ± 3 vs 3 ± 4 pmol/L; P = 0.027). Isoglycemia was achieved using 35 ± 12 g of intravenous glucose in patients with cirrhosis compared with 24 ± 10 g in healthy controls (P = 0.003). The gastrointestinal-mediated glucose disposal was markedly lower in patients with cirrhosis (30 ± 23 vs 52 ± 20%; P = 0.003). Despite higher levels of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic peptide patients with cirrhosis had reduced incretin effect (35 ± 44 vs 55 ± 30%; P = 0.008). CONCLUSION: Impaired gastrointestinal-mediated glucose disposal and reduced incretin effect may contribute to the glucose intolerance seen in patients with cirrhosis.
BACKGROUND AND AIM: The impaired glucose tolerance in cirrhosis is poorly understood. We evaluated the influence of gastrointestinal-mediated glucose disposal and incretin effect in patients with cirrhosis. METHODS:Non-diabeticpatients with Child-Pugh A or B cirrhosis (n = 10) and matched healthy controls (n = 10) underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion. We presented data as median ± interquartile range and compared groups using non-parametric analysis of variance. RESULTS:Patients with cirrhosis were glucose intolerant compared with healthy controls (4-h OGTTAUC : 609 ± 458 vs 180 ± 155 min × mmol/L; P = 0.005), insulin resistant (homeostatic model assessment for insulin resistance: 3.7 ± 4.9 vs 2.6 ± 1.4; P = 0.014) and had fasting hyperglucagonemia (8 ± 3 vs 3 ± 4 pmol/L; P = 0.027). Isoglycemia was achieved using 35 ± 12 g of intravenous glucose in patients with cirrhosis compared with 24 ± 10 g in healthy controls (P = 0.003). The gastrointestinal-mediated glucose disposal was markedly lower in patients with cirrhosis (30 ± 23 vs 52 ± 20%; P = 0.003). Despite higher levels of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic peptide patients with cirrhosis had reduced incretin effect (35 ± 44 vs 55 ± 30%; P = 0.008). CONCLUSION: Impaired gastrointestinal-mediated glucose disposal and reduced incretin effect may contribute to the glucose intolerance seen in patients with cirrhosis.
Authors: Lili Niu; Philipp E Geyer; Nicolai J Wewer Albrechtsen; Lise L Gluud; Alberto Santos; Sophia Doll; Peter V Treit; Jens J Holst; Filip K Knop; Tina Vilsbøll; Anders Junker; Stephan Sachs; Kerstin Stemmer; Timo D Müller; Matthias H Tschöp; Susanna M Hofmann; Matthias Mann Journal: Mol Syst Biol Date: 2019-03-01 Impact factor: 11.429