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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes Mellitus; Metabolic Syndrome; Hyperlipidemia; Arterial Hypertension
• Intervention / Treatment: Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Medicinsk forskningslaboratorium, Aarhus Universitet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• 18-70 years of age
• Member of Biobank Vejle
• BMI<30

Exclusion Criteria:

• Diabetes mellitus
• Severe illness

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carriers	Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer; 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.
Experimental: Non-carriers	Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; University of Copenhagen; Lundbeck Foundation; Vejle Hospital; Steno Diabetes Center Copenhagen; Hospital of South West Jutland
• Investigators: Principal Investigator: Niels Møller, Professor, University of Aarhus; Principal Investigator: Oluf B Pedersen, Professor, Steno Diabetes Center Copenhagen; Principal Investigator: Torben Hansen, Professor, Steno Diabetes Center Copenhagen; Principal Investigator: Jørgen Rungby, Professor, University of Aarhus

Publications and helpful links

General Publications

• Stoy J, Kampmann U, Mengel A, Magnusson NE, Jessen N, Grarup N, Rungby J, Stodkilde-Jorgensen H, Brandslund I, Christensen C, Hansen T, Pedersen O, Moller N. Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG: a novel genometabolic cross-link between CD300LG and common metabolic phenotypes. BMJ Open Diabetes Res Care. 2015 Aug 26;3(1):e000095. doi: 10.1136/bmjdrc-2015-000095. eCollection 2015.
• Stoy J, Grarup N, Horlyck A, Ibsen L, Rungby J, Poulsen PL, Brandslund I, Christensen C, Hansen T, Pedersen O, Moller N, Kampmann U. Blood pressure levels in male carriers of Arg82Cys in CD300LG. PLoS One. 2014 Oct 14;9(10):e109646. doi: 10.1371/journal.pone.0109646. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: April 3, 2012
• First Submitted That Met QC Criteria: April 4, 2012
• First Posted (Estimate): April 5, 2012

Study Record Updates

• Last Update Posted (Estimate): December 2, 2014
• Last Update Submitted That Met QC Criteria: December 1, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Lipid Metabolism Disorders; Dyslipidemias; Hypertension; Metabolic Syndrome; Hyperlipidemias; Metabolic Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 1-10-72-113-12