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

July 9, 2014 updated by: Jonatan I Bagger, University Hospital, Gentofte, Copenhagen
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Observational

Enrollment (Actual)

48

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Hellerup, Denmark, 2900
        • Diabetes Research Division, Gentofte University Hospital, Niels Andersens Vej 65, opgang 4b, 1. sal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with NAFLD and liver cirrhosis confirmed by liver biopsy, and patients with or without well characterized type 2 diabetes recruited in the the hospitals out patients clinic

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
NAFLD
Non alcoholic fatty liver disease without type 2 diabetes
Other: OGTT
50g waterfree glucose dissolved in 300 ml water consumed over 5 min.
Other Names:
  • Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Names:
  • Glucose infusion, 20%
NAFLD+T2D
Non alcoholic fatty liver disease with type 2 diabetes
Other: OGTT
50g waterfree glucose dissolved in 300 ml water consumed over 5 min.
Other Names:
  • Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Names:
  • Glucose infusion, 20%
T2D
Type 2 diabetics without non alcoholic fatty liver disease
Other: OGTT
50g waterfree glucose dissolved in 300 ml water consumed over 5 min.
Other Names:
  • Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Names:
  • Glucose infusion, 20%
cirrhosis
Patients with liver cirrhosis
Other: OGTT
50g waterfree glucose dissolved in 300 ml water consumed over 5 min.
Other Names:
  • Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Names:
  • Glucose infusion, 20%
Kontrol groups
Healthy control subjects
Other: OGTT
50g waterfree glucose dissolved in 300 ml water consumed over 5 min.
Other Names:
  • Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Names:
  • Glucose infusion, 20%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Incretin effect
Time Frame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma Glucagon like peptide 1 (GLP-1) response
Time Frame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose
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
Plasma Glucose-dependent insulinotropic peptide (GIP) response
Time Frame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose
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
Plasma glucagon response
Time Frame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Gentofte, Copenhagen

Investigators

  • Principal Investigator: Anders E Junker, MD, phd-student, Diabetes Research Division, Gentofte Hospital, University of Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2011

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

December 5, 2011

First Submitted That Met QC Criteria

December 13, 2011

First Posted (Estimate)

December 14, 2011

Study Record Updates

Last Update Posted (Estimate)

July 10, 2014

Last Update Submitted That Met QC Criteria

July 9, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LINK-1-2011
  • H-1-2011-082 (Other Identifier: The Danish National Committee on Biomedical Research Ethics)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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