Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia

Not Applicable

Completed

• Conditions: Non-alcoholic Fatty Liver Disease
• Interventions: Procedure: Liver biopsy; Other: Pancreatic clamp

• Registration Number: NCT02337660
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

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.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-01-08
• Study First Submitted QC: 2015-01-12
• Study First Posted: 2015-01-13
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-14
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy, lean	Liver biopsy	15 healthy, lean subjects. Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Obese, otherwise healthy	Liver biopsy	15 obese, otherwise healthy subjects Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Obese, otherwise healthy	Pancreatic clamp	15 obese, otherwise healthy subjects Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Healthy, lean	Pancreatic clamp	15 healthy, lean subjects. Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.

Primary Outcome Measures

Name	Time	Method
Amino acid metabolism	0-180 min
Endogenous glucose production	0-180 min

Secondary Outcome Measures

Name	Time	Method
Degree of steatosis	baseline
Total RNA sequencing of liver biopsies	baseline

Trial Locations

Locations (1)

Center for Diabetes Research; 🇩🇰 Gentofte, Denmark