Clinical trial NCT06193668: Overfeeding Induced Fat-tissue Stimulation
Official title: Short-term High-fat Overnutrition Induces Insulin Resistance in White Adipose Tissue
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lipid-induced Insulin Resistance
Lead sponsor: German Diabetes Center
Sponsor class: OTHER
Collaborators: name: Yale University
First posted: 2024-01-05
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Type 2 diabetes is the most common metabolic disease worldwide, characterized by hyperglycemia, decreased whole body insulin sensitivity, and white adipose tissue (WAT) dysfunction. A key factor in its development is chronic overnutrition, usually with a high-fat diet (HFD), leading to disturbances of glucose and lipid metabolism. However, the mechanism of short-term HFD-induced tissue-specific insulin resistance remains poorly understood. This project aims to further unravel the underlying mechanisms of short-term HFD overnutrition-mediated WAT insulin resistance. The model described here corresponds to a randomized, single- blinded parallel-grouped trial, consisting of two interventions: a macronutrient-balanced diet and or a hypercaloric diet over three weeks in order to investigate differences in interorgan fatty acid and glucose metabolism between the studied groups. Based on recent studies, the hypothesis is that 21-day hypercaloric HFD induces WAT insulin resistance via a diacylglycerol, novel protein kinase C-insulin receptor signaling model in both fasting and insulin-stimulated states.


Eligibility criteria: Inclusion Criteria:

* Age between 18 and 40 years
* BMI \< 29 kg/m2
* Sport inactive (\<1x /week)
* Capacity to consent

Exclusion Criteria:

* Diabetes mellitus disease
* Acute coronary heart syndrome (myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack in the last 3 months before study participation)
* Acute infectious disease
* Taking blood glucose-lowering drugs
* Diseases or drugs affecting the immune system and allergies to drugs used in the study
* Drugs with potential metabolic effects
* Chronic liver disease (hepatitis, gallbladder disease, elevated liver enzymes (ALT \> 300 U/L))
* Chronic inflammatory bowel diseases
* Rheumatic diseases
* Hyper- or hypothyroidism of the thyroid gland
* Renal insufficiency, administration of iodine-containing contrast media in the last 2 days
* Chronic lung diseases
* cancerous diseases
* Addictive diseases, psychiatric diseases
* Pregnancy, breastfeeding
* Shift workers
* Anemia (Hb \<12 g/dl)
* Disorders of hemostasis
* Regular use of antithrombotic drugs
* Alcohol consumption, smoking
* Conditions that do not permit an MRI examination

Primary outcomes:
measure: Whole-body insulin sensitivity and WAT insulin sensitivity
timeFrame: 3 weeks intervention period each
Secondary outcomes:
measure: WAT insulin signaling pathways
timeFrame: 3 weeks intervention time
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: Georgia Xourafa
state: Nordrhein-Westfalen
Study officials:
affiliation: German Diabetes Center
name: Michael Roden, Prof., MD
role: STUDY_DIRECTOR
References: