Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia

November 14, 2018 updated by: Malte Palm Suppli, University Hospital, Gentofte, Copenhagen
The purpose of this study is to examine whether non-alcoholic fatty liver disease (NAFLD) is associated with hepatic glucagon resistance and hyperglucagonemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

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
      • Gentofte, Denmark, 2900
        • Center for diabetes research

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

25 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

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

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Healthy, lean

15 healthy, lean subjects.

Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Procedure: Liver biopsy
One ultrasound guided liver biopsy
Other: Pancreatic clamp
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.
Experimental: Obese, otherwise healthy

15 obese, otherwise healthy subjects

Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Procedure: Liver biopsy
One ultrasound guided liver biopsy
Other: Pancreatic clamp
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Endogenous glucose production
Time Frame: 0-180 min
0-180 min
Amino acid metabolism
Time Frame: 0-180 min
0-180 min

Secondary Outcome Measures

Outcome Measure
Time Frame
Degree of steatosis
Time Frame: baseline
baseline
Total RNA sequencing of liver biopsies
Time Frame: baseline
baseline

Collaborators and Investigators

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

Sponsor

University Hospital, Gentofte, Copenhagen

Collaborators

The Novo Nordisk Foundation Center for Basic Metabolic Research

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

January 1, 2015

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

January 8, 2015

First Submitted That Met QC Criteria

January 12, 2015

First Posted (Estimate)

January 13, 2015

Study Record Updates

Last Update Posted (Actual)

November 16, 2018

Last Update Submitted That Met QC Criteria

November 14, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SIRG-1

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.

Clinical Trials on Non-alcoholic Fatty Liver Disease

Clinical Trials on Liver biopsy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Romania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe