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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jonatan I Bagger, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01492283
First received: December 5, 2011
Last updated: July 9, 2014
Last verified: July 2014
  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 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided

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
Study First Received: December 5, 2011
Last Updated: July 9, 2014
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics

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

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Fatty Liver
Liver Cirrhosis
Fibrosis
Liver Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Pathologic Processes
Gastric Inhibitory Polypeptide
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014