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Fat and Transcapillary Insulin Transport (FATRAIN)

This study has been completed.
Sponsor:
Collaborator:
Medical University of Vienna
Information provided by (Responsible Party):
julia szendrödi, German Diabetes Center
ClinicalTrials.gov Identifier:
NCT01482455
First received: November 27, 2011
Last updated: September 7, 2012
Last verified: September 2012
History of Changes
  Purpose

There is a current debate whether impaired insulin-mediated microvascular perfusion limits the delivery of hormones and nutrients to muscle and whether short term FFA elevation affects transcapillary transport of insulin and glucose thereby representing a rate-controlling step for insulin-stimulated muscular glucose disposal in humans.

To address these questions, the investigators determined the changes of interstitial glucose and insulin in skeletal muscle of healthy volunteers during intravenous administration of triglycerides or glycerol under physiologic and supraphysiologic hyperinsulinemic conditions.


Condition Intervention
Lipid-induced Insulin Resistance
 Other: Elevation of FFA during OGTT
Other: Elevation of FFA during Clamp

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Lipid-induced Insulin Resistance is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by German Diabetes Center:

Primary Outcome Measures:
  • Blood flow [ Time Frame: between the start of the lipid/glycerol infusion until the end of the study (360 min) ] [ Designated as safety issue: No ]
    Regional blood flow. Muscular blood flow will be measured by the laser Doppler flow technique (LDF, Moor Instruments, Devon, UK) as described previously


Secondary Outcome Measures:
  • Interstitial insulin concentration [ Time Frame: between the start of the lipid/glycerol infusion until the end of the study (360 min) ] [ Designated as safety issue: No ]
    Interstitial insulin concentration in skeletal muscle is measured via microdialysis based on sampling of analytes from the interstitial space fluid by means of a dialysis membrane at the tip of a microdialysis probe.


Enrollment: 8
Study Start Date: December 2011
Study Completion Date: August 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Clamp/Glycerol
Glycerol infusion (glycerol in 0.9% saline provided by the pharmacy of the Vienna General Hospital, will be applied at a rate of 0.7 mg.kg-1.min-1) in order to match the lipid-induced rise in serum glycerol concentrations in the same experimental setting. 0-240 min: Intralipid® 20%, Pharmacia AB, Stockholm, Sweden, 90 ml/hr; Heparin "Immuno"®, Immuno AG, Vienna, Austria, bolus: 200IU, continuous infusion: 0.2 IU.kg-1.min-1. After two hours, a hyperinsulinemic-euglycemic clamp (Actrapid, Novo Nordisk, Bagsvaerd, Denmark; 40 mU.m-2 body surface area min-1) test will be commenced (120-240 min).
 Other: Elevation of FFA during Clamp
0-240 min: Intralipid® 20%, Pharmacia AB, Stockholm, Sweden, 90 ml/hr; Heparin "Immuno"®, Immuno AG, Vienna, Austria, bolus: 200IU, continuous infusion: 0.2 IU.kg-1.min-1.
Active Comparator: OGTT/Lipid
On study-day 1, four hours after start of a triglyceride/heparin infusion an oral glucose tolerance test (OGTT, 75g glucose dissolved in 300ml flavoured water) will be performed (240-420 min).
 Other: Elevation of FFA during OGTT
0-240 min: Intralipid® 20%, Pharmacia AB, Stockholm, Sweden, 90 ml/hr; Heparin "Immuno"®, Immuno AG, Vienna, Austria, bolus: 200IU, continuous infusion: 0.2 IU.kg-1.min-1
Placebo Comparator: OGTT/Glycerol
On study-day 2, four hours after start of a glycerol infusion an oral glucose tolerance test (OGTT, 75g glucose dissolved in 300ml flavoured water) will be performed (240-420 min).
 Other: Elevation of FFA during OGTT
0-240 min: Intralipid® 20%, Pharmacia AB, Stockholm, Sweden, 90 ml/hr; Heparin "Immuno"®, Immuno AG, Vienna, Austria, bolus: 200IU, continuous infusion: 0.2 IU.kg-1.min-1
Active Comparator: Clamp/Lipid
0-240 min: Intralipid® 20%, Pharmacia AB, Stockholm, Sweden, 90 ml/hr; Heparin "Immuno"®, Immuno AG, Vienna, Austria, bolus: 200IU, continuous infusion: 0.2 IU.kg-1.min-1. After two hours, a hyperinsulinemic-euglycemic clamp (Actrapid, Novo Nordisk, Bagsvaerd, Denmark; 40 mU.m-2 body surface area min-1) test will be commenced (120-240 min).
 Other: Elevation of FFA during Clamp
0-240 min: Intralipid® 20%, Pharmacia AB, Stockholm, Sweden, 90 ml/hr; Heparin "Immuno"®, Immuno AG, Vienna, Austria, bolus: 200IU, continuous infusion: 0.2 IU.kg-1.min-1.

Detailed Description:

Increased lipid availability reduces insulin-stimulated glucose disposal in skeletal muscle, which is generally explained by lipid induced inhibition of myocellular insulin signalling, It remains unclear whether lipids also impair transcapillary transport of insulin and glucose which could thereby become rate-controlling for glucose disposal Increased accumulation and availability of lipids cause impaired skeletal muscle insulin sensitivity. It is yet unclear if transcapillary transport of insulin and glucose is impaired by acute elevation of free fatty acids and represents a rate-limiting step during the development of short-term lipid-induced insulin resistance. We determined the changes of interstitial glucose and insulin in skeletal muscle of healthy volunteers during intravenous administration of triglycerides and heparin or glycerol under physiologic and supraphysiologic hyperinsulinemic conditions.

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • The volunteers have to be older than 19 years,
  • nonobese (body mass index, BMI less than 27 kg/m2),
  • normolipidemic (fasting serum concentration of triglycerides < 140 mg/dL and
  • total cholesterol < 200 mg/dL) and
  • non-smokers.

Exclusion Criteria:

  • The following exclusion criteria will be applied:

    • any medication within two weeks prior to the start of study,
    • regular alcohol consumption > 40 g/d,
    • acute inflammatory disease defined by serum C-reactive protein > 1 mg/dL,
    • abnormalities in the screening visit or in laboratory tests considered as clinically relevant,
    • family history of diabetes mellitus or dyslipidemia,
    • glucose intolerance,
    • allergy or hypersensitivity against study medication,
    • blood clotting disorders.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01482455

Locations
Austria
Medical University Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
German Diabetes Center
Medical University of Vienna
  More Information

No publications provided

Responsible Party: julia szendrödi, MD, PhD, German Diabetes Center
ClinicalTrials.gov Identifier: NCT01482455     History of Changes
Other Study ID Numbers: FATRAIN
Study First Received: November 27, 2011
Last Updated: September 7, 2012
Health Authority: Austria: Medical University of Vienna

Keywords provided by German Diabetes Center:
Insulin resistance
vascular impairment
diabetes

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Glycerol
Insulin
 Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hypoglycemic Agents

ClinicalTrials.gov processed this record on May 22, 2013