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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01492283
First Posted: December 14, 2011
Last Update Posted: July 10, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Jonatan I Bagger, University Hospital, Gentofte, Copenhagen
  Purpose
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.

Condition Intervention
Non Alcoholic Fatty Liver Disease Type 2 Diabetes Liver Cirrhosis Other: OGTT Other: IIGI

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pathophysiological Implications of the Incretin Hormones in Patients With Liver Disease With and Without Diabetes

Resource links provided by NLM:


Further study details as provided by Jonatan I Bagger, University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.

  • 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.

  • 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.


Biospecimen Retention:   Samples With DNA
DNA (whole blood) will be kept for 15 years

Enrollment: 48
Study Start Date: December 2011
Study Completion Date: July 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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 Name: Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Name: 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 Name: Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Name: 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 Name: Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Name: Glucose infusion, 20%
cirrhosis
Patients with liver cirrhosis
Other: OGTT
50g waterfree glucose dissolved in 300 ml water consumed over 5 min.
Other Name: Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Name: Glucose infusion, 20%
Kontrol groups
Healthy control subjects
Other: OGTT
50g waterfree glucose dissolved in 300 ml water consumed over 5 min.
Other Name: Waterfree glucose, The Pharmacy of the capital region
Other: IIGI
iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose
Other Name: Glucose infusion, 20%

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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01492283


Locations
Denmark
Diabetes Research Division, Gentofte University Hospital, Niels Andersens Vej 65, opgang 4b, 1. sal
Hellerup, Denmark, 2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Investigators
Principal Investigator: Anders E Junker, MD, phd-student Diabetes Research Division, Gentofte Hospital, University of Copenhagen
  More Information

Responsible Party: Jonatan I Bagger, MD PhD-student, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01492283     History of Changes
Other Study ID Numbers: LINK-1-2011
H-1-2011-082 ( Other Identifier: The Danish National Committee on Biomedical Research Ethics )
First Submitted: December 5, 2011
First Posted: December 14, 2011
Last Update Posted: July 10, 2014
Last Verified: July 2014

Keywords provided by Jonatan I Bagger, University Hospital, Gentofte, Copenhagen:
NAFLD
Incretin hormones

Additional relevant MeSH terms:
Diabetes Mellitus
Liver Diseases
Fatty Liver
Liver Cirrhosis
Non-alcoholic Fatty Liver Disease
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Hormones
Gastric Inhibitory Polypeptide
Incretins
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Gastrointestinal Agents