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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

November 27, 2011
September 7, 2012
December 2011
March 2012   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01482455 on ClinicalTrials.gov Archive Site
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.
Same as current
Not Provided
Not Provided
 
Fat and Transcapillary Insulin Transport
Lipid-induced Insulin Resistance is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans

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.

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.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Lipid-induced Insulin Resistance
  • 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
  • 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.
  • 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).
    Intervention: Other: Elevation of FFA during Clamp
  • 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).
    Intervention: Other: Elevation of FFA during OGTT
  • 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).
    Intervention: Other: Elevation of FFA during OGTT
  • 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).
    Intervention: Other: Elevation of FFA during Clamp
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
8
August 2012
March 2012   (final data collection date for primary outcome measure)

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.
Male
20 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Austria
 
NCT01482455
FATRAIN
No
julia szendrödi, German Diabetes Center
German Diabetes Center
Medical University of Vienna
Not Provided
German Diabetes Center
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP