Free Fatty Acid Induced Insulin Resistance

Insulin Resistance Clinical Trial

— FFAIR  

Official title:

Assessment of the Time Course of Lipid Induced Insulin Resistance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01229059
• Other study ID #: FFAIR
• Status: Completed
• Start date: March 2010
• Est. completion date: November 2019

Study information

• Verified date: August 2023
• Source: German Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to explore time-dependent effects of lipid infusion an intramyocellular lipid metabolites and the induction of impaired insulin signaling.

Description:

Increased availability of free fatty acids impairs glucose disposal in young healthy humans. Patients with type 2 diabetes have reduced whole body glucose disposal, increased ectopic lipid deposition in skeletal muscle and the liver and impaired mitochondrial function. Recent studies suggest that lipid metabolites such as diacylglycerol (DAG), ceramides and long-chain acyl-coA represent the active mediators inducing insulin resistance. Possible targets are DAG-sensitive Proteinkinase C (PKC θ, PKC ε) which inhibit the insulin signaling cascade and ceramides which interfere with the insulin signaling cascade at Proteinkinase B/AKT. Prior studies raised controvesial evidence, thus, it is yet unclear, whether DAG or ceramides are the primary agents inducig lipid-induced insulin resistance. Therefore, the current study aims to explore the time course of the appearance of intramyocellular lipid compunds during lipid infusion in parallel assessing markers of impaired insulin action.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: November 2019
• Est. primary completion date: November 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 55 Years

Eligibility

Inclusion Criteria:

• non-diabetic (OGTT), no family history of diabetes, BMI<30 kg/m2, age: 20-55 years, no medication

For the athletes group additionally:

• VO2max > 60ml/kg/min for males and VO2max > 45ml/kg/min for females Active in endurance-exercise activities, 3 times a week for at least 2 years Stable level of training for at least 3 months

Exclusion Criteria:

• acute illness within the last 2 weeks, autoimmune diseases, renal insufficiency (creatinine> 1.5 mg/dl), cardiovascular diseases, anemia (Hb< 12g/l), donation of blood within the last 4 weeks before the study, thyroid diseases, pregnancy, smoking, night-shift working (disturbed circadian rhythm), defective coagulation or wound healing, cancer, allergy against soja products

Related Conditions & MeSH terms

• Insulin Resistance

Intervention

Dietary Supplement:
• Lipovenös lipid infusion
Lipid enriched infusions will be applied for 2-6 hours.

Locations

Country	Name	City	State
Germany	German Diabetes Center	Duesseldorf	NRW

Sponsors (2)

Lead Sponsor	Collaborator
German Diabetes Center	Heinrich-Heine University, Duesseldorf

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	intramyocellular lipid metabolites	Muscle biopsies are taken before, after 2.5 and 4 hours of lipid infusion	after 4 hours lipid infusion
Primary	muscle glucose flux	glycogen synthesis rate, glucose-6-phosphate	during lipid infusion
Secondary	insulin resistance of glucose uptake and mitochondrial function	Mitochondrial function will bes assessed from muscle biopsy samples taken after 4 hours, insulin sensitivity will be assessed from hyperinsulinemic-euglycemic clamps following 4 hours lipid infusion	after 4 hours lipid infusion