Fat and Transcapillary Insulin Transport (FATRAIN)

German Diabetes Center

Status: Completed

Conditions: Lipid-induced Insulin Resistance

Treatments: Other: Elevation of FFA during Clamp; Other: Elevation of FFA during OGTT

Study type: Interventional

Funder types: Other

Identifiers

NCT01482455

FATRAIN

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: Male

Ages: 20 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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8 participants in 4 patient groups, including a placebo group

Clamp/Glycerol

Placebo Comparator group

Description:

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).

Treatment:

Other: Elevation of FFA during Clamp

OGTT/Lipid

Active Comparator group

Description:

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).

Treatment:

Other: Elevation of FFA during OGTT

OGTT/Glycerol

Placebo Comparator group

Description:

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).

Treatment:

Other: Elevation of FFA during OGTT

Clamp/Lipid

Active Comparator group

Description:

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).

Treatment:

Other: Elevation of FFA during Clamp