Overfeeding Induced Fat-tissue Stimulation

Lipid-induced Insulin Resistance Clinical Trial

— OVID_FASTI  

Official title:

Short-term High-fat Overnutrition Induces Insulin Resistance in White Adipose Tissue

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06193668
• Other study ID #: OVID-FASTI
• Status: Recruiting
• Phase: N/A
• Start date: January 31, 2024
• Est. completion date: December 31, 2030

Study information

• Verified date: February 2024
• Source: German Diabetes Center
• Contact: Theresia Sarabhai, MD
• Phone: 0173-9473478
• Email: theresia.sarabhai[@]ddz.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Insulin Resistance
• Lipid-induced Insulin Resistance

Intervention

Behavioral:
• High-fat overnutrition
Overnutrition: 40% higher lipid consumption per day than required
• Normocaloric macronutrient-balanced nutrition
Normocaloric, macronutrient-balanced nutrition: Calories requirement for weight maintenance [(kcal/d) 55% carbohydrates, 15% proteins, 30% fat]

Locations

Country	Name	City	State
Germany	Georgia Xourafa	Düsseldorf	Nordrhein-Westfalen

Sponsors (2)

Lead Sponsor	Collaborator
German Diabetes Center	Yale University

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Whole-body insulin sensitivity and WAT insulin sensitivity	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.	3 weeks intervention period each
Secondary	WAT insulin signaling pathways	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.	3 weeks intervention time