Non-alcoholic Fatty Liver Disease
Conditions
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.
Interventions
PROCEDURELiver biopsy
One ultrasound guided liver biopsy
OTHERPancreatic 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.
Sponsors
The Novo Nordisk Foundation Center for Basic Metabolic Research
University Hospital, Gentofte, Copenhagen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Endogenous glucose production | 0-180 min |
| Amino acid metabolism | 0-180 min |
Secondary
| Measure | Time frame |
|---|---|
| Degree of steatosis | baseline |
| Total RNA sequencing of liver biopsies | baseline |
Countries
Denmark
Outcome results
None listed