Free Fatty Acid Induced Insulin Resistance

Completed

• Conditions: Insulin Resistance
• Interventions: Dietary Supplement: Lipovenös lipid infusion

• Registration Number: NCT01229059
• Lead Sponsor: German Diabetes Center

Brief Summary

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

Detailed 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.

Study Timeline

• Study Start: 2010-03
• Study First Submitted: 2010-03-20
• Study First Submitted QC: 2010-10-26
• Study First Posted: 2010-10-27
• Primary Completion: 2019-11
• Study Completion: 2019-11
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-11
• Last Update Posted: 2023-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
lipid infusion in untrained humans	Lipovenös lipid infusion	healthy lean humans before and after lipid infusion
lipid infusion in athletes	Lipovenös lipid infusion	endurance trained atheletes

Primary Outcome Measures

Name	Time	Method
intramyocellular lipid metabolites	after 4 hours lipid infusion	Muscle biopsies are taken before, after 2.5 and 4 hours of lipid infusion
muscle glucose flux	during lipid infusion	glycogen synthesis rate, glucose-6-phosphate

Secondary Outcome Measures

Name	Time	Method
insulin resistance of glucose uptake and mitochondrial function	after 4 hours lipid infusion	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

Trial Locations

Locations (1)

German Diabetes Center; 🇩🇪 Duesseldorf, NRW, Germany