Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Non-alcoholic Fatty Liver Disease

Treatments: Procedure: Liver biopsy; Other: Pancreatic clamp

Study type: Interventional

Funder types: Other

Identifiers

NCT02337660

SIRG-1

Details and patient eligibility

About

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

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 25 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Healthy, lean

Experimental group

Description:

15 healthy, lean subjects. Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.

Treatment:

Other: Pancreatic clamp

Procedure: Liver biopsy

Obese, otherwise healthy

Experimental group

Description:

15 obese, otherwise healthy subjects Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.

Treatment:

Other: Pancreatic clamp

Procedure: Liver biopsy