Clinical trial NCT02337660: Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia
Official title: Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: The Novo Nordisk Foundation Center for Basic Metabolic Research
First posted: 2015-01-13
Enrollment: 30
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Endogenous glucose production
timeFrame: 0-180 min
measure: Amino acid metabolism
timeFrame: 0-180 min
Secondary outcomes:
measure: Degree of steatosis
timeFrame: baseline
measure: Total RNA sequencing of liver biopsies
timeFrame: baseline
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Center for Diabetes Research
Study officials:
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