Effects of Obesity and Intensity of Exercise on Ghrelin Levels

Obesity Clinical Trial

Official title:

Modulation of Ghrelin Release by Exercise Intensity: The Role of Obesity and Prediabetes Status

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04581980
• Other study ID #: 200241
• Secondary ID: 5R01DK129510-02
• Status: Recruiting
• Phase: N/A
• Start date: October 14, 2020
• Est. completion date: July 2024

Study information

• Verified date: May 2023
• Source: University of Virginia
• Contact: Arthur Weltman, PhD
• Phone: (434) 924-6191
• Email: ALW2V[@]hscmail.mcc.virginia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is investigating the effect of different intensities of exercise on levels of the hormone, ghrelin. In addition, we will be examining the relationship between any exercise induced changes in ghrelin and insulin sensitivity, obesity, and vascular function.

Description:

The goal of this proposal is to characterize the effects of two exercise "intensity doses" on total ghrelin, acyl ghrelin, and des-acyl ghrelin in lean and obese adults with and without prediabetes. Ghrelin (TG) is involved in the regulation of appetite, energy balance, glucose metabolism and insulin sensitivity. Ghrelin exists in the blood in a des-acyl form (DAG ~78% of TG), and in an acylated form (AG ~22% of TG). Despite being less abundant, AG is has multiple actions that promote energy storage, including stimulation of appetite, inhibition of insulin release from the pancreas, and increases in adiposity via a widely characterized growth hormone secretagogue receptor. Conversely, DAG often opposes AG promoting negative energy balance (appetite suppression and reduced fat mass (FM)) and improving insulin sensitivity, acting through a receptor not yet identified. The optimal ratios of TG, DAG, and AG are not clear. Likewise, there is a need for targeted approaches that can effectively manipulate these peptides to aid in the prevention and/or treatment of obesity, metabolic syndrome, prediabetes and type 2 diabetes. Exercise provides a unique therapeutic approach in the treatment of dysregulated ghrelin. Limited animal and human studies examining exercise and ghrelin release are mostly equivocal or only document TG and/or a single (e.g. AG) form of ghrelin. As DAG and AG can act synergistically, antagonistically, or have independent effects, the quantification of these peptides in response to exercise is critical to understanding the role of exercise on ghrelin release and ghrelin's exercise induced influence on overall glucose regulation and energy balance. Exercise intensity may be key, as exercise that elevates levels of lactate suppress AG and appetite post exercise. Here we propose to address this gap in knowledge by defining the role of acute exercise intensity, at doses above and below the lactate threshold, on TG, AG, and DAG release in lean and obese individuals with and without prediabetes. Specific Aim 1: Examine effects of exercise intensity on ghrelin, insulin, glucose and self-reported appetite. Hypothesis: Higher exercise intensity will result in differential effects on TG, AG, DAG, AG/DAG, insulin, and glucose AUC's, and appetite; affected by sex, obesity, abdominal visceral fat (AVF), and prediabetes status. Specific Aim 2: This is an exploratory aim using regression modeling to examine exercise-induced changes in ghrelin on glucose, insulin and appetite. Hypothesis: TG, AG, DAG and AG/DAG alterations will differentially predict changes in glucose metabolism, insulin sensitivity, and appetite. These alterations vary by sex, levels of obesity, AVF, and prediabetes. Results from this pilot/feasibility application will inform a larger submission that defines therapeutic exercise targets for TG, AG, and DAG, and examines the effects of individualized exercise training using precision exercise prescription techniques on ghrelin release.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 18-55 years of age
• BMI between 18-40 kg/m2
• Untrained (reports less than 2 days/week of exercise)
• Weight stable (no significant loss/gain of more than 3kg in the past 3 months)
• Females must be premenopausal and report normal menstrual cycles

Exclusion Criteria:

• History of diabetes, gastrointestinal disease, or endocrine disorder
• Smoking (must have quit at least 6 months prior)
• Disordered eating
• Females currently pregnant or undergoing fertility treatments
• The following medications (due to their effect on insulin sensitivity ,endothelial function and/or ghrelin secretion): Synthetic growth hormone, metformin, synthetic insulin, sulfonylureas, meglitinides, Thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors , biguanides, alpha-glucosidase inhibitors, phosphodiesterase inhibitors, beta-blockers, alpha-blockers, ACE-inhibitors, ARB's, fibrates, glucocorticoids, olanzapine

Related Conditions & MeSH terms

• Cardiovascular Risk Factor
• Insulin Resistance
• Obesity

Intervention

Other:
• Exercise
Participants will exercise on a cycle ergometer

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
University of Virginia	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Insulin Sensitivity	We want to create a linear regression model to explore the relationship between exercise induced changes in ghrelin and insulin sensitivity	Insulin and glucose will be collected at 5 timepoints during the OGTT, and 11 timepoints during each testing visit. The Matsuda index (mathematical model) will be used to calculate insulin sensitivity
Other	Body Composition	We want to create a linear regression model to explore the relationship between exercise induced changes in ghrelin and body composition (i.e. fat mass)	Body composition will be measured twice during a DEXA and CT scan (takes about 30 minutes)
Primary	Ghrelin	We will be analyzing plasma levels of acylated and deacylated ghrelin	Measured at 6 timepoints over 2-3 hours during each experimental visit
Secondary	Appetite Questionnaire (VAS)	We will see how appetite may or may not change in response to exercise	Measured at 6 timepoints over 2-3 hours during each experimental visit
Secondary	Vascular Function (brachial flow mediated dilation)	We will be measuring how the arteries respond (i.e. dilate) in response to exercise	Measured at 5 timepoints over 2-3 hours during each experimental visit