The Effects of Glucagon on Hepatic Metabolism

Obesity Clinical Trial

Official title:

The Effects of Glucagon on Hepatic Metabolism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05500586
• Other study ID #: 22-000113
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 20, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Mayo Clinic
• Contact: Jeanette Laugen
• Phone: 5072558110
• Email: Laugen.Jeanette[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell function, or a combination of both are important, unanswered questions. NAFLD is associated with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying degrees of hepatic steatosis).

Description:

T2DM and prediabetes are characterized by abnormal post-prandial suppression of glucagon, which contributes to postprandial hyperglycemia by increasing EGP. Although these effects are magnified by decreased and delayed insulin secretion, they are also apparent when insulin secretion is intact. In rodents, altered glucagon signaling changes α-cell function and mass - an effect mediated by changes in circulating AA concentrations. Are the elevated concentrations of branched-chain AA and other AA metabolites in T2DM a cause or an effect of global α-cell dysfunction? Could altered glucagon signaling precipitate a vicious cycle resulting in T2DM?

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria:

• Willing to participate
• Able to give consent

Exclusion Criteria:

• History of prior upper abdominal surgery e.g. gastric banding, pyloroplasty, vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.
• Contraindications to MRI (e.g. metal implants, claustrophobia).
• Hematocrit < 35%
• TSH < 0.4 or > 5.5.
• Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire

Related Conditions & MeSH terms

• NAFLD
• Obesity

Intervention

Drug:
• Glucagon response study
Please see information in group descriptions

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Adrian Vella

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Amino acid catabolism in the presence / absence of glucagon	Tracer-dependent measurement of amino-acid clearance	240 minutes of study
Secondary	Effect of Diabetes on amino-acid catabolism	Tracer-dependent measurement of amino-acid clearance	240 minutes of study

External Links

•   Mayo Clinic Clinical Trials