Fat and Transcapillary Insulin Transport

Lipid-induced Insulin Resistance Clinical Trial

— FATRAIN  

Official title:

Lipid-induced Insulin Resistance is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01482455
• Other study ID #: FATRAIN
• Status: Completed
• Phase: N/A
• Start date: December 2011
• Est. completion date: August 2012

Study information

• Verified date: September 2012
• Source: German Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: August 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Insulin Resistance
• Lipid-induced Insulin Resistance

Intervention

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
• 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.

Locations

Country	Name	City	State
Austria	Medical University Vienna	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
German Diabetes Center	Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood flow	Regional blood flow. Muscular blood flow will be measured by the laser Doppler flow technique (LDF, Moor Instruments, Devon, UK) as described previously	between the start of the lipid/glycerol infusion until the end of the study (360 min)
Secondary	Interstitial insulin concentration	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.	between the start of the lipid/glycerol infusion until the end of the study (360 min)