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

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

Detailed Description
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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.

Official Title
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Hyperglucagonaemia in Patients With Type 2 Diabetes - Role of Glucagon Clearance

Conditions
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Diabetes

Intervention / Treatment
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* Biological: Glucagon


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Glucagon, Metabolic clearance rate of glucagon