Effect of High Caloric Diet on Brain Insulin Sensitivity and Inflammation

Einfluss Von Hochkalorischer Nahrungsaufnahme Auf Die Insulinsensitivität Des Menschlichen Zentralnervensystems

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes Mellitus, Type 2
• Intervention / Treatment: Other: High caloric diet

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • University of Tuebingen, Department of Internal Medicine IV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 29 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• BMI 19-24 kg/m2

  • Non smoking
  • normal glucose tolerance during 75g oral glucose tolerance test (OGTT)
  • Exercise less than 2h per week

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High caloric diet; Participants will eat 1500 kcal more than their usual diet for five days.	Other: High caloric diet; After dietary counseling, subjects will receive high caloric snacks for five days.
No Intervention: Control diet; Participants will eat regular diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in whole-body insulin sensitivity	Insulin sensitivity will be estimated from a frequent-sampling 75 g oral glucose tolerance test using the Matsuda formula.	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	Body composition will be addressed by whole-body MRI and liver MRS.	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	Memory function, food reward behavior and mood will be assessed by questionnaires, neuropsychological testing and a snack test.	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	Insulin secretion will be estimated from a frequent-sampling 75 g oral glucose tolerance test.	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.

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2018
• Primary Completion (Actual): March 10, 2020
• Study Completion (Actual): March 10, 2020

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: July 5, 2018
• First Posted (Actual): July 18, 2018

Study Record Updates

• Last Update Posted (Actual): May 20, 2020
• Last Update Submitted That Met QC Criteria: May 19, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 813/2017BO2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We will not able to share individual participant data due to data protection restraints.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No