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

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Non Alcoholic Fatty Liver Disease; Liver Cirrhosis; Type 2 Diabetes

Treatments: Other: IIGI; Other: OGTT

Study type: Observational

Funder types: Other

Identifiers

NCT01492283

LINK-1-2011

H-1-2011-082 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 48 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

48 participants in 5 patient groups

NAFLD

Description:

Non alcoholic fatty liver disease without type 2 diabetes

Treatment:

Other: OGTT

Other: IIGI

NAFLD+T2D

Description:

Non alcoholic fatty liver disease with type 2 diabetes

Treatment:

Other: OGTT

Other: IIGI

T2D

Description:

Type 2 diabetics without non alcoholic fatty liver disease

Treatment:

Other: OGTT

Other: IIGI

cirrhosis

Description:

Patients with liver cirrhosis

Treatment:

Other: OGTT

Other: IIGI

Kontrol groups

Description:

Healthy control subjects

Treatment:

Other: OGTT

Other: IIGI