Fat and Transcapillary Insulin Transport

Not Applicable

Completed

• Conditions: Lipid-induced Insulin Resistance
• Interventions: Other: Elevation of FFA during Clamp; Other: Elevation of FFA during OGTT

• 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

Arm && Interventions

Group	Intervention	Description
Clamp/Lipid	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. 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).
OGTT/Lipid	Elevation of FFA during OGTT	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).
Clamp/Glycerol	Elevation of FFA during Clamp	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).
OGTT/Glycerol	Elevation of FFA during OGTT	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).

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