Metabolic dysfunction in patients with metabolic fatty liver disease (MAFLD) may increase the risk for diabetes development. The liver is essential for the postprandial control of our metabolism and hormonal response, yet most studies focus on fasting conditions. We therefore studied the fasting and postprandial phase in individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD, (n = 9, mean age 50 y, mean BMI 35 kg/m2, no/mild fibrosis) , cirrhosis (n = 10, age 62 y, BMI 32 kg/m2, CHILD A/B) and healthy controls (n = 10, age 23, BMI 25 kg/m2) , randomized 1:1 to fasting or Nutridrink (Nutricia, 300 kcal) . None of the postprandial patients had type 2 diabetes (T2D) . In the NAFLD/cirrhosis groups, 17/classified as MAFLD. Peripheral blood samples were collected at 0, 15, 45, 60, 90 and 120 minutes. At time point 60, a transjugular liver biopsy and liver vein blood were taken. Levels of glucose, insulin, C-peptide, glucagon, and fibroblast growth factor 21 (FGF21) were measured in peripheral blood, glucagon and FGF21 also in liver vein blood. Postprandial peak glucose and C-peptide was increased in NAFLD and cirrhosis compared with healthy (mean peak glucose (mM) 7, 10, 6; mean peak C-peptide (pM) 2675, 3340, 1689, respectively) . The postprandial incremental AUC for insulin was significantly increased in patients with NAFLD compared to healthy. Patients with NAFLD and cirrhosis had hyperglucagonemia, a phenotype related to prediabetes. FGF21 was increased in NAFLD and cirrhosis and correlated to age (r= .61, P = .001) and fasting glucose (r = .54, P = .006) . Glucagon levels were higher in liver vein compared to peripheral blood, while FGF21 levels were similar in both compartments.

In summary, patients with NAFLD and cirrhosis without T2D showed significant metabolic dysfunction after a standardized meal compared to healthy controls. We found impaired glucose tolerance, hyperinsulinemia and hyperglucagonemia in both NAFLD and cirrhosis, suggesting a condition of prediabetes in patients with MAFLD.

Disclosure

J. Grandt: None. A.H. Jensen: None. M.P. Werge: None. E.B. Rashu: None. A. Junker: None. L. Hobolth: None. C. Mortensen: 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 was financed by NNF Excellence Emerging Investigator Grant – Endocrinology and Metabolism (Application No. NNF19OC0055001) , EFSD Future Leader Award (NNF21SA0072746) and DFF Sapere Aude.

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