Hyperglucagonaemia in Patients With Type 2 Diabetes - Role of Glucagon Clearance (MCR Glucagon)

The study aims to evaluate the elimination and degradation of glucagon in patients with type 2 diabetes compared to matched healthy subjects.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Biological: Glucagon

Detailed Description

In the present project the investigators wish to identify whether the elimination and degradation of glucagon differ between healthy control subjects and patients with type 2 diabetes. Furthermore, the investigators wish to examine whether obesity is an independent factor for altered glucagon metabolism. Thus, by examining glucagon elimination in obese subjects with and without type 2 diabetes and in lean subjects with and without type 2 diabetes the investigators will be able to describe the metabolic clearance rate (MCR) of glucagon in a broad spectrum of individuals with different levels of insulin resistance and beta cell dysfunction.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Hellerup, Copenhagen, Denmark, 2900
      • Center for Diabetes Research, Department of Medicine, Gentofte Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients with type 2 diabetes

• Caucasians above 35 years of age with diet or/and metformin-treated type 2 diabetes of at least 3 month duration (diagnosed according to World Health Organization (WHO) criteria
• BMI either below 27 or above 33 kg/m^2
• Normal haemoglobin
• Informed consent

Subjects with NGT

• Caucasians above 35 years of age
• BMI either below 27 or above 33 kg/m^2
• Normal HbA1c (according to WHO criteria)
• Normal haemoglobin
• Informed consent

Exclusion Criteria:

Patients with type 2 diabetes

• Inflammatory bowel disease
• Operation within the last 3 months
• Severe kidney disease (eGFR < 60 ml/min)
• Severe liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2×normal values)
• Pregnancy and/or breastfeeding
• Age above 80 years
• Any condition that the investigators feel would interfere with trial participation

Subjects with NGT

• Diabetes
• Prediabetes (impaired FPG or HbA1c above 42 mmol/mol)
• First-degree relatives with diabetes
• Inflammatory bowel disease
• Intestinal resection
• Severe kidney disease (eGFR < 60 ml/min)
• Liver disease (ALA T and/or serum ASA T >2×normal values)
• Pregnancy and/or breastfeeding
• Age above 80 years Any condition that the investigators feel would interfere with trial participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy, lean subjects; Healthy subjects with BMI < 27 kg/m^2	Biological: Glucagon; One hour glucagon-clamp followed by one hour of blood sampling
Experimental: Healthy, obese subjects; Healthy subjects with BMI > 33 kg/m^2	Biological: Glucagon; One hour glucagon-clamp followed by one hour of blood sampling
Experimental: Diabetic, lean subjects; Diabetic subjects with BMI < 27 kg/m^2	Biological: Glucagon; One hour glucagon-clamp followed by one hour of blood sampling
Experimental: Diabetic, obese subjects; Diabetic subjects with BMI > 33 kg/m^2	Biological: Glucagon; One hour glucagon-clamp followed by one hour of blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Metabolic clearance rate of glucagon	-30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes

Secondary Outcome Measures

Outcome Measure	Time Frame
Gut and pancreatic hormones	-30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Blood glucose	-30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Basic metabolic rate	-30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Satiety, hunger, appetite - measured with visual analogue scales (VAS)	-30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Half life of glucagon	-30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
The volume of distribution of glucagon	-30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: University of Copenhagen; European Foundation for the Study of Diabetes

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: June 11, 2015
• First Submitted That Met QC Criteria: June 17, 2015
• First Posted (Estimate): June 18, 2015

Study Record Updates

• Last Update Posted (Actual): October 15, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes; Glucagon; Metabolic clearance rate of glucagon
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucagon
• Other Study ID Numbers: H-1-2014-066