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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01492283
• Other study ID #: LINK-1-2011
• Secondary ID: H-1-2011-082
• Status: Completed
• Phase: N/A
• First received: December 5, 2011
• Last updated: July 9, 2014
• Start date: December 2011
• Est. completion date: July 2014

Study information

• Verified date: July 2014
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: July 2014
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Fatty Liver
• Liver Cirrhosis
• Liver Diseases
• Non Alcoholic Fatty Liver Disease
• Type 2 Diabetes

Intervention

Other:
• OGTT
50g waterfree glucose dissolved in 300 ml water consumed over 5 min.
• IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose

Locations

Country	Name	City	State
Denmark	Diabetes Research Division, Gentofte University Hospital, Niels Andersens Vej 65, opgang 4b, 1. sal	Hellerup

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose	No
Secondary	Plasma Glucagon like peptide 1 (GLP-1) response	Comparing GLP-1 responses of the different experimental days, compared to healthy control subjects.	pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose	No
Secondary	Plasma Glucose-dependent insulinotropic peptide (GIP) response	Comparing GIP responses of the different experimental days, compared to healthy control subjects.	pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose	No
Secondary	Plasma glucagon response	Comparing glucagon responses of the different experimental days, compared to healthy control subjects.	pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose	No