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
Sex
ALL
Min age
18 Years
Max age
40 Years
Healthy volunteers
Accepted
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 outcome measure(s)
Whole-body insulin sensitivity and WAT insulin sensitivity — 3 weeks intervention period each Hyperinsulinemica-euglycemia clamp tests with deuterated glucose to measure fasting and insulin-stimulated whole-body insulin sensitivity and measurement of the index ADIPO-IR (fasting insulin x free fatty acid concentration) before and after dietary intervention period.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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