Pathophysiological Implications of the Incretin Hormones in Patients With Liver Disease With and Without Diabetes

University Hospital, Gentofte, Copenhagen48 enrolled

Overview

The main objective of this study is to analyze the pathophysiological implications of glucagon and the incretin hormones in patients with liver disease (Non alcoholic fatty liver disease (NAFLD) or cirrhosis) with and without diabetes compared with healthy controls. The present study will contribute significantly to the understanding of the pathophysiology of liver disease and glucose metabolism. The final goal is that the results could pave the way for new treatment modalities for patients with liver disease.

Comparison of of insulin secretion (Area Under the Curve (AUC)) during the experimental days. Furthermore a comparison of GIP, GLP1 and glucagon responses as well as plasma glucose levels.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Non Alcoholic Fatty Liver Disease Type 2 Diabetes Liver Cirrhosis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

I) Group 1: NAFLD patients with normal glucose tolerance Inclusion criteria * NAFLD verified by a liver biopsy * Caucasian \>18 years of age * Negative islet cell (ICA) and glutamic acid decarboxylase 65 (GAD65) autoantibodies * Normal 75-g OGTT as specified in the WHO Criteria * Normal haemoglobin and blood pressure (BP) * Written informed consent II) Group 2: NAFLD patients with type 2 diabetes Inclusion criteria * NAFLD verified by liver biopsy * T2DM according to the WHO Criteria * Caucasian \>18 years of age * Negative ICA and GAD65, normal haemoglobin, normal BP * Written informed consent III) Group 3: NAFLD patients without type 2 diabetes Inclusion criteria * NAFLD verified by liver biopsy * Caucasian \>18 years of age * Normal 75-g OGTT * Negative ICA and GAD65-autoantibodies * Normal haemoglobin and BP * Written informed consent IV) Group 4: Cirrhosis with or without type 2 diabetes Inclusion criteria * Liver cirrhosis verified by liver biopsy * Caucasian \> 18 years of age * Negative ICA and GAD65-autoantibodies * Normal haemoglobin and BP * Written informed consent V) Group 5: Healthy controls Inclusion criteria * Caucasian \>18 years of age * Normal 75-g OGTT according to the WHO Criteria * Negative ICA and GAD65-autoantibodies * Normal haemoglobin and BP * Written informed consent Exclusion criteria (all groups) * Other known liver disease - viral hepatitis, hereditary haemochromatosis, autoimmune liver disease, alpha-1 trypsin deficiency, Wilson disease, drug induced liver Injury (DILI) * Treatment with medications that cannot be discontinued for 12 hours * Unwillingness to participate in protocols * Pregnancy or lactation

Outcomes

Primary Outcomes

The Incretin effect

The difference in insulin responses, as assessed by the area under curve (AUC) for plasma insulin and C-peptide concentrations, during the two different glucose stimuli: Oral glucose tolerance test (OGTT) and isoglycemic iv glucose infusion in NAFLD patients with and without diabetes, and cirrhotic patients compared to healthy control subjects

Time frame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose

Secondary Outcomes

Plasma Glucagon like peptide 1 (GLP-1) response

Comparing GLP-1 responses of the different experimental days, compared to healthy control subjects.

Time frame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose

Plasma Glucose-dependent insulinotropic peptide (GIP) response

Comparing GIP responses of the different experimental days, compared to healthy control subjects.

Time frame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose

Plasma glucagon response

Comparing glucagon responses of the different experimental days, compared to healthy control subjects.

Time frame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose

Pathophysiological Implications of the Incretin Hormones in Patients With Liver Disease With and Without Diabetes

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes