1338-P: Glucoregulatory Disturbances in Autoimmune Liver Disease and Nonalcoholic Fatty Liver Disease Compared with Healthy Individuals

Abstract

Gluco-regulatory disturbances such as hepatic insulin resistance, hyperinsulinemia and prediabetes are commonly present in patients with nonalcoholic fatty liver disease (NAFLD) and those individuals may over time develop full-blown type 2 diabetes. Chronic liver diseases­ such as NAFLD and autoimmune liver diseases (AILDs) are heterogenous but may affect glucose-metabolism similarly. It is, however, unknown if AILDs—such as primary biliary cholangitis (PBC) —display gluco-regulatory impairments. We therefore investigated glucose and hormonal responses during a 75 g oral glucose tolerance test (OGTT) in patients with biopsy-verified, non-cirrhotic PBC (n = 9, age 55 ± y (mean ± sd) , BMI 31 ± 6 kg/m2 (mean ± sd)) , NAFLD (n = 6, age 38 ± 17 y, BMI 31 ± 4 kg/m2) and healthy controls (n = 8, age 23 ± 3 y, BMI 23 ± 2 kg/m2) . None of the participants had diabetes. In the PBC group, 3 had NAFLD. Fasting glucose, c-peptide and insulin levels were significantly increased in PBC and NAFLD compared with healthy controls ([mean (95 % CI) ]; glucose (mM) 5.6 (4.7-6.7) , 5.7 (5.2-6.1) , 4.7 (3.9-5.6) ; c-peptide (pM) 993 (556-1773) , 1334 (1036-1719) , 483 (268-869) ; insulin (pM) 98 (33-298) , 166 (103-267) , 43 (14-136) ; respectively) . Hepatic insulin resistance (reflected by fasting homeostasis model assessment of insulin resistance (HOMA-IR)) was present in PBC (mean 4.0 (95 % CI 1.2-13.9)) and NAFLD (7.0 (4.1-11.9)) but not in healthy controls (1.5 (0.4-5.4)) . There was no significant difference in glucose levels between the groups. Beta-cell secretion (c-peptide) was significantly increased in PBC and NAFLD. Insulin responses were higher in PBC and NAFLD compared with healthy but only reached statistical significance in NAFLD. Our data suggest that patients with PBC have gluco-regulatory disturbances including hepatic insulin resistance and impaired beta-cell function. Metabolic dysfunction of PBC may be underestimated and warrant further investigation. Disclosure A.H. Jensen: None. H. Ytting: Other Relationship; Gilead Sciences, Inc. J. Grandt: None. M.P. Werge: None. E.B. Rashu: None. L.E. Hetland: None. A. Junker: None. L. Hobolth: None. C. Mortensen: None. F. Tofteng: None. M. Vyberg: None. R. Serizawa: Consultant; Merck Sharp & Dohme Corp. L. Gluud: Advisory Panel; Novo Nordisk. Consultant; Pfizer Inc. Research Support; Alexion Pharmaceuticals, Inc., Gilead Sciences, Inc., Novo Nordisk, Sobi. N.J. Wewer Albrechtsen: Research Support; Mercodia AB, Novo Nordisk, Regeneron Pharmaceuticals Inc. Speaker’s Bureau; Merck & Co., Inc., Mercodia AB. Funding Nicolai J. Wewer Albrechtsen were financed by NNF Excellence Emerging Investigator Grant – Endocrinology and Metabolism (Application No. NNF19OC0055001) , EFSD Future Leader Award (NNF21SA0072746) and DFF Sapere Aude