Free Fatty Acid Induced Insulin Resistance (FFAIR)

Assessment of the Time Course of Lipid Induced Insulin Resistance

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

Study Overview

• Status: Completed
• Conditions: Insulin Resistance
• Intervention / Treatment: Dietary supplement: Lipovenös lipid infusion

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 Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Duesseldorf, NRW, Germany, 40225
      • German Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Healthy, lean non-diabetic humans

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
lipid infusion in untrained humans; healthy lean humans before and after lipid infusion	Dietary supplement: Lipovenös lipid infusion; Lipid enriched infusions will be applied for 2-6 hours.; Other Names: soy oil
lipid infusion in athletes; endurance trained atheletes	Dietary supplement: Lipovenös lipid infusion; Lipid enriched infusions will be applied for 2-6 hours.; Other Names: soy oil

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: German Diabetes Center
• Collaborators: Heinrich-Heine University, Duesseldorf
• Investigators: Principal Investigator: Michael Roden, Prof., MD, German Diabetes Center

Publications and helpful links

General Publications

• Phielix E, Begovatz P, Gancheva S, Bierwagen A, Kornips E, Schaart G, Hesselink MKC, Schrauwen P, Roden M. Athletes feature greater rates of muscle glucose transport and glycogen synthesis during lipid infusion. JCI Insight. 2019 Nov 1;4(21):e127928. doi: 10.1172/jci.insight.127928.
• Fritsch M, Koliaki C, Livingstone R, Phielix E, Bierwagen A, Meisinger M, Jelenik T, Strassburger K, Zimmermann S, Brockmann K, Wolff C, Hwang JH, Szendroedi J, Roden M. Time course of postprandial hepatic phosphorus metabolites in lean, obese, and type 2 diabetes patients. Am J Clin Nutr. 2015 Nov;102(5):1051-8. doi: 10.3945/ajcn.115.107599. Epub 2015 Sep 30.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2010
• Primary Completion (Actual): November 1, 2019
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: March 20, 2010
• First Submitted That Met QC Criteria: October 26, 2010
• First Posted (Estimated): October 27, 2010

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: mitochondria; insulin resistance; FFA
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: FFAIR