Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia

Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia

The purpose of this study is to examine whether non-alcoholic fatty liver disease (NAFLD) is associated with hepatic glucagon resistance and hyperglucagonemia.

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.

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