Fat and Transcapillary Insulin Transport

NCT01482455 | Completed

• 1 other identifier: FATRAIN
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Lipid-induced Insulin Resistance

Keywords

Insulin resistance; vascular impairment; diabetes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Interstitial insulin concentration

  between the start of the lipid/glycerol infusion until the end of the study (360 min)

Study Arms (4)

Clamp/Glycerol

PLACEBO COMPARATOR

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

OGTT/Lipid

ACTIVE COMPARATOR

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

OGTT/Glycerol

PLACEBO COMPARATOR

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

Clamp/Lipid

ACTIVE COMPARATOR

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

Interventions

Elevation of FFA during OGTT OTHER

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

OGTT/Glycerol; OGTT/Lipid

Elevation of FFA during Clamp OTHER

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.

Clamp/Glycerol; Clamp/Lipid

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• German Diabetes Center: lead
• Medical University of Vienna: collaborator

Study Sites (1)

Medical University Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Insulin Resistance; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Michael Roden, Prof., MD

  German Diabetes Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2011
• First Posted: November 30, 2011
• Study Start: December 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: August 1, 2012
• Last Updated: June 15, 2023

Record last verified: 2012-09

Locations

AU (1)