Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia

University Hospital, Gentofte, Copenhagen30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Liver biopsyPROCEDURE

One ultrasound guided liver biopsy

Pancreatic clampOTHER

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.

Eligibility

Sex: ALLMin age: 25 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Center for Diabetes Research

Gentofte Municipality, Denmark

Outcomes

Primary Outcomes

Endogenous glucose production

Time frame: 0-180 min

Amino acid metabolism

Time frame: 0-180 min

Secondary Outcomes

Degree of steatosis

Time frame: baseline

Total RNA sequencing of liver biopsies

Time frame: baseline

Data from ClinicalTrials.gov

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