Fat and Transcapillary Insulin Transport

Not Applicable

Completed

• Conditions: Lipid-induced Insulin Resistance

• Registration Number: NCT01482455
• Lead Sponsor: German Diabetes Center

Brief 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.

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.

Study Timeline

• Study First Submitted: 2011-11-27
• Study First Submitted QC: 2011-11-29
• Study First Posted: 2011-11-30
• Study Start: 2011-12
• Primary Completion: 2012-03
• Study Completion: 2012-08
• Status Verified: 2012-09
• Last Update Submitted: 2023-06-13
• Last Update Posted: 2023-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 8

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Blood flow	between the start of the lipid/glycerol infusion until the end of the study (360 min)	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

Name	Time	Method
Interstitial insulin concentration	between the start of the lipid/glycerol infusion until the end of the study (360 min)	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.

Trial Locations

Locations (1)

Medical University Vienna; 🇦🇹 Vienna, Austria