Baseline Physiology Studies in Carriers of Gene Variant X Conferring Major Risk of CVD-prone Metabolic Disorders

Study Overview
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Brief Summary
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The purpose of the present study is to conduct a thorough and relevant physiology study of carriers and non-carriers of the gene variant X in order to determine the effect of the genetic variant on various metabolic parameters.

Official Title
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Baseline Physiology Studies in Carriers of Gene Variant X Conferring Major Risk of CVD-prone Metabolic Disorders

Conditions
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Hyperlipidemia, Diabetes Mellitus, Metabolic Syndrome, Arterial Hypertension, Obesity

Intervention / Treatment
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* Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male 18-70 years of age Member of Biobank Vejle BMI<30 Exclusion Criteria: Diabetes mellitus Severe illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

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: Carriers<br> | Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer<br>* FPIR: intravenous infusion of 20 % glucose 0.3 mg/kg in 2 minutes followed by blood sampling at times 0, 2, 4, 6, 8, and 10. Duration 10 minutes. HEC: intravenous infusion of actrapid 1mU/kg/minute, simultaneous infusion of 20 % glucose at variable rate to reach plasma blood glucose level of 5 mmol/L. Duration 120 minutes Glucose tracer: bolus of 3H3glucose (12µCi) followed by infusion of 3H3glucose (0,12 µCi/min). Duration 120 minutes. Palmitate tracer:[9,10-3H]-palmitate 0,3 µCi/min. Duration 60 minutes.<br>|
| Experimental: Non-carriers<br> | Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer<br>* FPIR: intravenous infusion of 20 % glucose 0.3 mg/kg in 2 minutes followed by blood sampling at times 0, 2, 4, 6, 8, and 10. Duration 10 minutes. HEC: intravenous infusion of actrapid 1mU/kg/minute, simultaneous infusion of 20 % glucose at variable rate to reach plasma blood glucose level of 5 mmol/L. Duration 120 minutes Glucose tracer: bolus of 3H3glucose (12µCi) followed by infusion of 3H3glucose (0,12 µCi/min). Duration 120 minutes. Palmitate tracer:[9,10-3H]-palmitate 0,3 µCi/min. Duration 60 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin secretion | Estimation of first phase insulin secretion | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance | Estimation of insulin resistance using hyperinsulinemic euglycemic clamp and glucose and lipid tracers | 240 minutes | 
| body composition | Evaluation of body composition using Dxa scan and MRI scan | 60 minutes | 
| atherosclerosis | Evaluation of presence and severity of atherosclerosis using ultrasound scan of the common carotide artery | 30 minutes | 
| biochemical blood profiling | Various tests run on blood samples | at baseline | 
| Insulin resistance | Biopsi from muscle and adipose tissue performed at baseline and during clamp study. | 60 minutes | 
| Blood pressure | Measurement of blood pressure every 20. minutes/24 hours | 24 hours | 
| Indirect calorimetry | Estimation of resting energy expenditure and respiratory quotient | 60 minutes |