Clinical trial NCT01229059: Free Fatty Acid Induced Insulin Resistance
Official title: Assessment of the Time Course of Lipid Induced Insulin Resistance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Insulin Resistance
Keywords: FFA
insulin resistance
mitochondria
Lead sponsor: German Diabetes Center
Sponsor class: OTHER
Collaborators: name: Heinrich-Heine University, Duesseldorf
First posted: 2010-10-27
Enrollment: 55
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Healthy, lean non-diabetic humans

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.

Eligibility criteria: 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

Primary outcomes:
measure: intramyocellular lipid metabolites
timeFrame: after 4 hours lipid infusion
measure: muscle glucose flux
timeFrame: during lipid infusion
Secondary outcomes:
measure: insulin resistance of glucose uptake and mitochondrial function
timeFrame: after 4 hours lipid infusion
Other outcomes:
Locations:
city: Duesseldorf
country: Germany
facility: German Diabetes Center
state: NRW
Study officials:
affiliation: German Diabetes Center
name: Michael Roden, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.