Study of the Effects of Overfeeding on Glucocorticoids in Lean and Obese Subjects (Gluco-Food)

The Acute Response of Glucocorticoids Upon Food Intake

Investigators suggest that in lean subjects cortisol increases in response to overfeeding and that this increase is blunted in obese subjects. A group of 18 male healthy lean subjects and another group of 18 male healthy obese subjects will undergo a high-calorie meal test. Prior to the meal intake, an indirect calorimetry, bioelectrical impedance, heart rate variability, a fasting blood sample and a perceived stress questionnaire will be assessed. After intake of the study meal, blood tests will be performed in order to measure the secretion of cortisol, glucose and lipid metabolism and inflammatory markers. Indirect calorimetry will be assessed again 60 and 180 minutes after the meal intake.

Study Overview

• Status: Completed
• Conditions: Overweight and Obesity
• Intervention / Treatment: Other: High-calorie meal

Detailed Description

Obesity is one of the most serious health problems in the 21st century. High energy food and a sedentary lifestyle are driving the current obesity pandemic. These factors activate the hypothalamic-pituitary-adrenal (HPA) axis, the key regulatory pathway of energy homeostasis. Activation of the HPA-axis leads to secretion of glucocorticoids from the adrenal glands, which control energy homeostasis by mobilizing and redistributing energy substrates.

Animal models of obesity have shown that glucocorticoids play a key role in the development of the metabolic syndrome. However, studies in humans yielded conflicting results. These studies have a major limitation in common. They do not consider glucocorticoid rhythmicity but rather investigate a snapshot of glucocorticoid secretion. Rhythmicity, however, is crucial because already minor glucocorticoid phase disturbances cause disease and could contribute to obesity.

Interestingly, excessive food intake may increase cortisol levels in healthy subjects . The consequence of this food-induced cortisol peak is not understood, but it may be key to restoring energy homeostasis after a meal. Whether the food-induced cortisol peak in obese subjects is disturbed is not known

With this study, investigators aim to better understand the role played by glucocorticoids in the origin of overweight and obesity. Researchers will investigate, in lean and obese subjects, whether the pulsatile release of cortisol increases after intake of a high-calorie meal. 36 subjects will take part in the study: a group of 18 male lean subjects and a second group of 18 male obese patients.

• Study Type: Observational
• Enrollment (Actual): 36

Contacts and Locations

Study Locations

• Switzerland
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4031
      • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Community sample. The obese group will be both a community and a clinical sample.

Description

Inclusion Criteria:

• Body mass index (BMI) >18,5 and <25 kg/m2
• BMI >30 kg/m2

Exclusion Criteria:

• Any clinically significant concomitant diseases in lean subjects
• Any clinically significant concomitant diseases in obese subjects apart from features of the metabolic syndrome (dyslipidemia, arterial hypertension and insulin resistance)
• Lactose intolerance
• Severe food allergy
• Regular alcohol consumption (>30 g/d)
• Regular fitness training (>4 hours/week)
• Previous enrolment in a clinical trial within the last 3 months
• Inability or contradictions to undergo the investigated intervention
• Inability to follow the procedures of the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lean subjects; 24 hours before the study visit, participants will be asked to refrain from alcohol and strenuous exercise. Patients will be asked to remain fasted 10 hours before the study visit takes place. On the day of the study visit, patients will be admitted to the hospital and, after intake of the study meal, blood samples will be taken.	Other: High-calorie meal; Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.
Obese subjects; 24 hours before the study visit, participants will be asked to refrain from alcohol and strenuous exercise. Patients will be asked to remain fasted 10 hours before the study visit takes place. On the day of the study visit, patients will be admitted to the hospital and, after intake of the study meal, blood samples will be taken.	Other: High-calorie meal; Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulsatile secretion of cortisol in response to a high-calorie meal (nmol/l)	Blood test	195 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thyroid hormones (nmol/l)	Blood test	195 minutes
Growth Hormone (mIU/l)	Blood test	195 minutes
Catecholamines (pg/ml)	Blood test	195 minutes
Adrenocorticotropic Hormone (ACTH) (pg/ml)	Blood test	195 minutes
Glucagon-like-peptide-1 (GLP-1) (pg/ml)	Blood test	195 minutes
Gastric inhibitory polypeptide (GIP) (pg/ml)	Blood test	195 minutes
Peptide YY (PYY) (pg/ml)	Blood test	195 minutes
Glucose (mmol/l)	Blood test	195 minutes
Insulin (mIU/l)	Blood test	195 minutes
C-Peptide (pmol/l)	Blood test	195 minutes
Total cholesterol (mmol/l)	Blood test	195 minutes
Low density lipoprotein (LDL)-cholesterol (mmol/l)	Blood test	195 minutes
High density lipoprotein (HDL)-cholesterol (mmol/l)	Blood test	195 minutes
Triglycerides (mmol/l)	Blood test	195 minutes
Growth differentiation factor 15 (GDF15) (ng/l)	Blood test	195 minutes
High-sensitive c-reactive Protein (hsCRP) (mg/l)	Blood test	195 minutes
Interleukin-6 (IL-6) (pg/ml)	Blood test	195 minutes
Interleukin-8 (IL-8) (pg/ml)	Blood test	195 minutes
Interleukin-1 receptor Antagonist (IL-1Ra) (pg/ml)	Blood test	195 minutes
Heart rate (bpm)	Heart rate variability analysis	5 minutes
Blood pressure: diastolic and systolic blood pressure (mmHg)	Standard blood pressure monitor	1 minute
Weight: kilogram body weight (kg)	Standard scale	1 minute
Energy expenditure: basal metabolic rate	Indirect calorimetry	200 minutes
Substrate utilisation: respiratory quotient	Indirect calorimetry	200 minutes
Fat and lean mass (kg)	Body impedance analysis	20 minutes
Total body water (l)	Body impedance analysis	20 minutes
Appetite: visual analogue scale rating	Visual analogue scale	3 hours
Stress: perceived stress Levels (0-56)	Perceived stress questionnaire	5 minutes

Collaborators and Investigators

• Sponsor: Eleonora Seelig
• Collaborators: Novartis
• Investigators: Principal Investigator: Eleonora Seelig, MD, University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

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• van der Klaauw AA, Farooqi IS. The hunger genes: pathways to obesity. Cell. 2015 Mar 26;161(1):119-132. doi: 10.1016/j.cell.2015.03.008.
• Vgontzas AN, Lin HM, Papaliaga M, Calhoun S, Vela-Bueno A, Chrousos GP, Bixler EO. Short sleep duration and obesity: the role of emotional stress and sleep disturbances. Int J Obes (Lond). 2008 May;32(5):801-9. doi: 10.1038/ijo.2008.4. Epub 2008 Feb 5.
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• Ibrahim M, Bonfiglio S, Schlogl M, Vinales KL, Piaggi P, Venti C, Walter M, Krakoff J, Thearle MS. Energy Expenditure and Hormone Responses in Humans After Overeating High-Fructose Corn Syrup Versus Whole-Wheat Foods. Obesity (Silver Spring). 2018 Jan;26(1):141-149. doi: 10.1002/oby.22068. Epub 2017 Nov 28.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2020
• Primary Completion (Actual): February 20, 2021
• Study Completion (Actual): February 20, 2021

Study Registration Dates

• First Submitted: March 30, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: obesity; overweight; cortisol; glucocorticoids; overfeeding
• Additional Relevant MeSH Terms: Body Weight; Overweight
• Other Study ID Numbers: 202000384

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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