Glucagon Suppression by Hyperglycemia in the Presence and Absence of Amino Acid Infusion

Healthy Clinical Trial

Official title:

Glucagon Suppression by Hyperglycemia in the Presence and Absence of Amino Acid Infusion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05264727
• Other study ID #: 22-000306
• Secondary ID: R01DK116231
• Status: Recruiting
• Phase: Phase 4
• Start date: May 30, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to better understand how amino acids alter the release of glucagon and insulin compared to glucose alone in health and disease.

Description:

T2DM and prediabetes are characterized by abnormal post-prandial suppression of glucagon, which contributes to postprandial hyperglycemia by increasing endogenous glucose production (EGP). 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? To measure glucagon secretion, as well as glucagon action, we have developed a population model of glucagon kinetics allowing us to deconvolve secretion from glucagon concentrations in a manner similar to Van Cauter's model for insulin secretion from C-peptide. This enables better characterization of α-cell function in humans. In addition to our novel methodology, we can characterize α-cell responsiveness to a graded glucose infusion, by quantifying (G50) - the change in glucose concentration necessary to suppress glucagon secretion by 50%. These experiments will determine if the glucagon secretion in response to AA differs in obese individuals with T2DM from that observed in obese individuals without T2DM.

Recruitment information / eligibility

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

Eligibility

Inclusion Criteria - Obese Subjects with Type 2 Diabetes:

• HbA1c = 8.5% (type 2 diabetic subjects).
• HbA1c = 6.5% (obese and lean subjects).
• BMI = 28 Kg/M^2 (Obese subjects with and without type 2 diabetes).
• BMI = 25 Kg/M^2 (Lean subjects without type 2 diabetes).
• Use of sulfonylureas or metformin only (type 2 diabetec subjects).
• For female subjects: negative pregnancy test at the time of enrollment or study.
• No history of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
• No active systemic illness or malignancy.
• No symptomatic macrovascular or microvascular disease.
• No 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 negative AUDIT questionnaire.

Exclusion Criteria - Obese Subjects with Type 2 Diabetes:

• HbA1c ³ 8.5%
• BMI = 28 Kg/M2
• Use of insulin or agents other than sulfonylureas or metformin.
• For female subjects: positive pregnancy test at the time of enrollment or study
• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and 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.

Inclusion Criteria - Obese Subjects without Type 2 Diabetes:

• BMI = 28 Kg/M2.
• > 5% liver fat content, as determined by MRI using the proton density fat fraction (PDFF) technique.

Exclusion Criteria - Obese Subjects without Type 2 Diabetes:

• HbA1c = 6.5%
• BMI = 28 Kg/M2
• Use of any glucose-lowering agents including metformin or sulfonylureas.
• For female subjects: positive pregnancy test at the time of enrollment or study
• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and 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.

Inclusion Criteria - Lean subjects without Diabetes:

• BMI = 25 Kg/M^2).

Exclusion Criteria - Lean Subjects without Diabetes:

• HbA1c = 6.5%.
• BMI = 25 Kg/M^2.
• Use of any glucose-lowering agents including metformin or sulfonylureas.
• For female subjects: positive pregnancy test at the time of enrollment or study.
• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and 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.
• Liver fat content = 5% as determined by MRI using the proton density fat fraction (PDFF) technique.

Related Conditions & MeSH terms

• Healthy
• Hyperglycemia
• Obesity
• Type 2 Diabetes

Intervention

Drug:
• Dextrose
Intravenous graded glucose infusion using 50% dextrose will commence at 1mg/kg/min and increase to 2 (0900), 4 (1000) and 8mg/kg/min (1100) every 60 minutes
• Clinisol 15%
Intravenous infusion 0.003ml/kg/min infused from 0 to 240 minutes

Locations

Country	Name	City	State
United States	Mayo Clinic Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	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
Primary	Change in Glucagon Suppression (G50) caused by amino acids vs. saline	concentration of glucose necessary to suppress glucagon by 50%	240 minutes of study
Secondary	Glucagon suppression (G50) is greater in people with T2DM	concentration of glucose necessary to suppress glucagon by 50%	240 minutes of study
Secondary	glucagon suppression (G50) is greater in obese compared to lean people without T2DM	concentration of glucose necessary to suppress glucagon by 50%	240 minutes of study

External Links

•   Mayo Clinic Clinical Trials