内科学
胰岛素抵抗
医学
内分泌学
自身免疫性肝炎
肝病
高葡萄糖血症
高胰岛素血症
肠促胰岛素
胰岛素
胰高血糖素
葡萄糖稳态
原发性硬化性胆管炎
糖尿病
2型糖尿病
疾病
作者
Anne‐Sofie H. Jensen,Henriette Ytting,Mikkel Werge,Elias B. Rashu,Liv Eline Hetland,Mira Thing,Puria Nabilou,Johan Burisch,Kirstine N. Bojsen‐Møller,Anders E Junker,Lise Hobolth,Christian Mortensen,Flemming Tofteng,Flemming Bendtsen,Søren Møller,Mogens Vyberg,Reza Serizawa,Lise Lotte Gluud,Nicolai J. Wewer Albrechtsen
出处
期刊:American Journal of Physiology-gastrointestinal and Liver Physiology
[American Physiological Society]
日期:2024-04-16
标识
DOI:10.1152/ajpgi.00047.2024
摘要
Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n=19), primary biliary cholangitis (PBC, n=15), and primary sclerosing cholangitis (PSC, n=6). Healthy individuals (n=24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n=18) were included as controls. Blood samples were collected during a 120 min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glucagon, the two incretin hormones glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clearance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses compared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. AIH and MASLD patients had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resulting in hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had an increased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoimmune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmune liver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.