Patients with autoimmune liver disease have glucose disturbances that mechanistically differ from steatotic liver disease
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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 ¼19), primary biliary cholangitis (PBC, n ¼ 15), and primary sclerosing cholangitis (PSC, n ¼ 6). Healthy individuals (n ¼ 24) andpatients with metabolic dysfunction-associated steatotic liver disease (MASLD, n ¼ 18) were included as controls. Blood sampleswere collected during a 120-min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glu-cagon, and the two incretin hormones, glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculatedthe homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clear-ance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses com-pared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. Patients with AIH andMASLD had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resultingin hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had anincreased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoim-mune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmuneliver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.
NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early onin their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.
NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early onin their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.
Originalsprog | Engelsk |
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Tidsskrift | American journal of physiology. Gastrointestinal and liver physiology |
Vol/bind | 326 |
Udgave nummer | 6 |
Sider (fra-til) | G736-G746 |
Antal sider | 11 |
ISSN | 0193-1857 |
DOI | |
Status | Udgivet - 2024 |
ID: 394438913