Overfeeding Induced Fat-tissue Stimulation

NCT06193668 | Recruiting

• 1 other identifier: OVID-FASTI
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Lipid-induced Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• WAT insulin signaling pathways

  3 weeks intervention time

Study Arms (2)

High-fat overnutrition

ACTIVE COMPARATOR

Lipid overnutrition: 40% higher lipid consumption per day than required over three weeks.

Behavioral: High-fat overnutrition

Normocaloric macronutrient-balanced nutrition

ACTIVE COMPARATOR

Normocaloric, macronutrient-balanced nutrition per day over three weeks

Behavioral: Normocaloric macronutrient-balanced nutrition

Interventions

High-fat overnutrition BEHAVIORAL

Overnutrition: 40% higher lipid consumption per day than required

High-fat overnutrition

Normocaloric macronutrient-balanced nutrition BEHAVIORAL

Normocaloric, macronutrient-balanced nutrition: Calories requirement for weight maintenance \[(kcal/d) 55% carbohydrates, 15% proteins, 30% fat\]

Normocaloric macronutrient-balanced nutrition

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• German Diabetes Center: lead
• Yale University: collaborator

Study Sites (1)

Georgia Xourafa

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Study Officials

• Michael Roden, Prof., MD

  German Diabetes Center

  STUDY DIRECTOR

Central Study Contacts

Theresia Sarabhai, MD

CONTACT

0173-9473478; theresia.sarabhai@ddz.de

Sabine Kahl, MD

CONTACT

0221-3382-; sabine.kahl@ddz.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: January 5, 2024
• Study Start: January 31, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 1, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)