Effect of High Caloric Diet on Brain Insulin Sensitivity and Inflammation

NCT03590561 | Completed

• 1 other identifier: 813/2017BO2
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity if known to be associated with brain insulin resistance in humans and evidence is rapidly accumulating that brain insulin resistance influences peripheral metabolism, eating behavior and cognition. A reduced insulin response in the brain is found mainly in people with a metabolically unfavorable fat distribution - high visceral fat. Visceral fat produces inflammatory mediators and elevated inflammatory levels are closely linked to insulin resistance. Inflammation of the brain (i.e., neuroinflammation) has been proposed as a possible cause of brain insulin resistance. Interestingly, rodent models of a high calorie diet show that these inflammatory mechanisms occur rapidly in the brain, even prior to weight gain of the animals. Among other things, it has been shown in humans that a short-term increase in calories, especially carbohydrates and fats, reduces insulin sensitivity in the body and increases inflammatory parameters in the blood. Whether a high-calorie diet triggers insulin resistance or inflammation in the human brain is currently unknown. Aim of study: The aim of the study is to investigate the effects of a five-day high calorie diet in healthy young male volunteers on peripheral and brain insulin sensitivity as well as on eating behavior, mood and cognition. Brain insulin sensitivity, peripheral metabolism and different behavioral assessments will be evaluated before, 1 week and 2 weeks after high caloric diet.

Conditions

Obesity; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (3)

• Change in brain insulin sensitivity

  fMRI measurement will be performed before and after administration of 160 U of human insulin as nasal spray. Changes in regional activity will be quantified to assess regional brain insulin sensitivity.

  Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet.

• Change in quantitative proton density

  The inflammatory processes in the brain will be measured through the quantification of the water content by means of proton density imaging.

  Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet.

• Change in brain metabolites

  The inflammatory processes in the brain will be measured through the determination of brain metabolites by MR spectroscopy

  Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet.

Secondary Outcomes (4)

• Change in whole-body insulin sensitivity

  Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control diet will start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet.

• Change in body fat distribution

  Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet.

• Behavioral assessment

  Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet.

• Change in insulin secretion

  Outcome measurements will be assessed at baseline (t0). Then, the 5-day high caloric diet or control dietwill start 5 to 30 days after t0. Outcome measurements will again be assessed on the 6th-7th day and on the 10th-15th day after start of diet.

Study Arms (2)

High caloric diet

EXPERIMENTAL

Participants will eat 1500 kcal more than their usual diet for five days.

Other: High caloric diet

Control diet

NO INTERVENTION

Participants will eat regular diet.

Interventions

High caloric diet OTHER

After dietary counseling, subjects will receive high caloric snacks for five days.

High caloric diet

Eligibility Criteria

• Age: 18 Years - 29 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI 19-24 kg/m2
• Non smoking
• normal glucose tolerance during 75g oral glucose tolerance test (OGTT)
• Exercise less than 2h per week

You may not qualify if:

• Vegetarians and Vegans
• Food allergies
• Working at night
• Professional Athletes
• Not removable metal parts in or on the body
• manifest cardiovascular disease
• claustrophobia
• recent surgery (less than 3 months)
• Simultaneous participation in other studies
• Acute disease or infection within the last 4 weeks
• neurological and psychiatric disorders
• treatment with centrally acting drugs
• hemoglobin Hb \<13g / dl
• Hypersensitivity to any of the substances used

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University of Tuebingen, Department of Internal Medicine IV

Tübingen, 72076, Germany

Location

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2018
• First Posted: July 18, 2018
• Study Start: June 13, 2018
• Primary Completion: March 10, 2020
• Study Completion: March 10, 2020
• Last Updated: May 20, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)