Overfeeding Induced Fat-tissue Stimulation

Not Applicable

Recruiting

• Conditions: Lipid-induced Insulin Resistance
• Interventions: Behavioral: High-fat overnutrition; Behavioral: Normocaloric macronutrient-balanced nutrition

• Registration Number: NCT06193668
• Lead Sponsor: German Diabetes Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-27
• Study First Submitted QC: 2024-01-04
• Study First Posted: 2024-01-05
• Study Start: 2024-01-31
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-29
• Last Update Posted: 2024-03-01
• Primary Completion: 2025-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High-fat overnutrition	High-fat overnutrition	Lipid overnutrition: 40% higher lipid consumption per day than required over three weeks.
Normocaloric macronutrient-balanced nutrition	Normocaloric macronutrient-balanced nutrition	Normocaloric, macronutrient-balanced nutrition per day over three weeks

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method
WAT insulin signaling pathways	3 weeks intervention time	Adipose tissue biopsies are planned to be taken during the fasting and insulin-stimulated state before and after the dietary intervention period. DAG and ceramide subcellular fractionation assay is planned to be performed. Expressionanalyses for activation /membrane translocation of novel and atypical protein kinase C isoforms will be done. Determination of the degree of phosphorylation of various components of the insulin pathway via Western blot are planned.

Trial Locations

Locations (1)

Georgia Xourafa; 🇩🇪 Düsseldorf, Nordrhein-Westfalen, Germany