Back to resultsInvolvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia
Primary Purpose
Non-alcoholic Fatty Liver Disease
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Liver biopsy
Pancreatic clamp
Sponsored by
About this trial
This is an interventional basic science trial for Non-alcoholic Fatty Liver Disease
Eligibility Criteria
Inclusion Criteria:
- Normal fasting plasma glucose and HbA1c < 6.0%
- Between 18.5 and 25 kg/m2 or between 30 and 40 kg/m2
- Normal haemoglobin
- Normal coagulation factor II, VII and X, INR and thrombocytes
- Age above 25 years
- Informed consent
Exclusion Criteria:
- Diabetes
- Prediabetes (impaired glucose tolerance and/or impaired fasting plasma glucose)
- First-degree relatives with diabetes
- Nephropathy (eGFR < 60ml/min and/or albuminuria)
- Liver disease (ALAT and/or serum ASAT >2x normal values)
- Use of anticoagulative medicine like Clopidogrel og Warfarin
- Pregnancy and/or breastfeeding
- Age above 80 years
- Any condition that the investigator feels would interfere with trial participation
Sites / Locations
- Center for Diabetes Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Healthy, lean
Obese, otherwise healthy
Arm Description
15 healthy, lean subjects. Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
15 obese, otherwise healthy subjects Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Outcomes
Primary Outcome Measures
Endogenous glucose production
Amino acid metabolism
Secondary Outcome Measures
Degree of steatosis
Total RNA sequencing of liver biopsies
Full Information
NCT ID
NCT02337660
First Posted
January 8, 2015
Last Updated
November 14, 2018
Sponsor
University Hospital, Gentofte, Copenhagen
Collaborators
The Novo Nordisk Foundation Center for Basic Metabolic Research
1. Study Identification
Unique Protocol Identification Number
NCT02337660
Brief Title
Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia
Official Title
Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Gentofte, Copenhagen
Collaborators
The Novo Nordisk Foundation Center for Basic Metabolic Research
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to examine whether non-alcoholic fatty liver disease (NAFLD) is associated with hepatic glucagon resistance and hyperglucagonemia.
Detailed Description
Hyperglucagonemia is a common condition in obesity, prediabetes and type 2 diabetes. It increases the hepatic glucose production, thus contributing to type 2-diabetic hyperglycemia. In the current study we wish to examine whether non-alcoholic fatty disease (NAFLD) results in hepatic glucagon resistance. This could result in hyperglucagonemia through a feedback mechanism acting on the level of pancreatic alpha cells. Cirrhosis and type 1 diabetes, respectively, has previously been shown to be associated with hepatic glucagon resistance but it has not been examined in relation to NAFLD in humans so far.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Fatty Liver Disease
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Healthy, lean
Arm Type
Experimental
Arm Description
15 healthy, lean subjects.
Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Arm Title
Obese, otherwise healthy
Arm Type
Experimental
Arm Description
15 obese, otherwise healthy subjects
Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Intervention Type
Procedure
Intervention Name(s)
Liver biopsy
Intervention Description
One ultrasound guided liver biopsy
Intervention Type
Other
Intervention Name(s)
Pancreatic clamp
Intervention Description
I.v. infusions of somatostatin and insulin (basal rate) for will be adminstered for 3 hours. Glucagon will administered for 3 hours in total with infusion rates at a basal and a high physiological rate for 1.5 hours each.
Primary Outcome Measure Information:
Title
Endogenous glucose production
Time Frame
0-180 min
Title
Amino acid metabolism
Time Frame
0-180 min
Secondary Outcome Measure Information:
Title
Degree of steatosis
Time Frame
baseline
Title
Total RNA sequencing of liver biopsies
Time Frame
baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Normal fasting plasma glucose and HbA1c < 6.0%
Between 18.5 and 25 kg/m2 or between 30 and 40 kg/m2
Normal haemoglobin
Normal coagulation factor II, VII and X, INR and thrombocytes
Age above 25 years
Informed consent
Exclusion Criteria:
Diabetes
Prediabetes (impaired glucose tolerance and/or impaired fasting plasma glucose)
First-degree relatives with diabetes
Nephropathy (eGFR < 60ml/min and/or albuminuria)
Liver disease (ALAT and/or serum ASAT >2x normal values)
Use of anticoagulative medicine like Clopidogrel og Warfarin
Pregnancy and/or breastfeeding
Age above 80 years
Any condition that the investigator feels would interfere with trial participation
Facility Information:
Facility Name
Center for Diabetes Research
City
Gentofte
ZIP/Postal Code
2900
Country
Denmark
12. IPD Sharing Statement
Citations:
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2121568
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Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia
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