Clinical trial NCT01482455: Fat and Transcapillary Insulin Transport
Official title: Lipid-induced Insulin Resistance is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lipid-induced Insulin Resistance
Keywords: Insulin resistance
vascular impairment
diabetes
Lead sponsor: German Diabetes Center
Sponsor class: OTHER
Collaborators: name: Medical University of Vienna
First posted: 2011-11-30
Enrollment: 8
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Blood flow
timeFrame: between the start of the lipid/glycerol infusion until the end of the study (360 min)
Secondary outcomes:
measure: Interstitial insulin concentration
timeFrame: between the start of the lipid/glycerol infusion until the end of the study (360 min)
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University Vienna
Study officials:
affiliation: German Diabetes Center
name: Michael Roden, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References: