Characterization of Natural IL-6 Inhibition in Healthy Individuals

Study Overview
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Brief Summary
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The aim of the project is to investigate whether or not there are any difference in cardiometabolic outcomes in individuals with high or low levels of c-aAb against interleukin-6 (IL-6). The study is the first to investigate individuals with extreme amounts of c-aAb levels against IL-6 and to contribute with knowledge on a possible new phenotype.

Official Title
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Characterization of Natural IL-6 Inhibition in Healthy Individuals

Conditions
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Autoantibodies, Interleukin-6

Intervention / Treatment
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* Other: Oral Glucose Tolerance Test
* Other: Cycling test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfill Danish blood donor criteria Have extreme amounts of IL-6 c-aAb or matched as control (low amounts of IL-6 c-aAb) Exclusion Criteria: Failure to fulfill Danish blood donor criteria
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
Interventional Model Description: Groups defined by autoantibodies status (high or low)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High IL-6 c-aAb<br>Individuals with top percentile IL-6 c-aAb | Other: Oral Glucose Tolerance Test<br>* 75g oral glucose tolerance test, sampled over three hours<br>Other: Cycling test<br>* 2 hours of moderate activity level cycling<br>|
| Experimental: Low IL-6 c-aAb<br>Individually matched controls with low IL-6 c-aAb | Other: Oral Glucose Tolerance Test<br>* 75g oral glucose tolerance test, sampled over three hours<br>Other: Cycling test<br>* 2 hours of moderate activity level cycling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory markers | IL-6 plasma levels, plasma IL-6 c-aAb levels | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Whole-body glucose metabolism | Plasma levels of: Insulin | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Whole-body glucose metabolism | Plasma levels of: C-peptide | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Whole-body glucose metabolism | Plasma levels of: Glucose | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Whole-body glucose metabolism | Plasma levels of: GLP-1 | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Whole-body glucose metabolism | Plasma levels of: GIPR | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Cardiovascular risk markers | Lipids | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Cardiovascular risk markers | Triglyceride | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Cardiovascular risk markers | Blood pressure | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Cardiovascular risk markers | Epicardial adipose tissue | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Difference in exercise response | 2-hour Lactate | Measurements over a two-hour cycling test, and one hour of recovery | 
| Difference in exercise response | 2-hour epinephrine | Measurements over a two-hour cycling test, and one hour of recovery | 
| Difference in exercise response | 2-hour norepinephrine | Measurements over a two-hour cycling test, and one hour of recovery | 
| Difference in exercise response | Peak IL-6 | Measurements over a two-hour cycling test, and one hour of recovery | 
| Metabolic response during exercise | 2-hour glucose | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Metabolic response during exercise | 2-hour glucagon | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Metabolic response during exercise | 2-hour insulin | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Metabolic response during exercise | 2-hour lipids | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Metabolic response during exercise | Triglyceride | Measurements over a three-hour oral glucose tolerance test, a two-hour cycling test, and one hour of recovery | 
| Metabolic assessment of the liver | Liver fat content from MRI-scanning, and HOMA-IR | An MRI-scanning withinn four weeks of the oral glucose tolerance test | 
| Metabolic assessment of the liver | HOMA-IR | An MRI-scanning withinn four weeks of the oral glucose tolerance test |