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

NCT ID: NCT05264727

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-30
• Study Completion Date: 2025-12-31

Brief 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.

Detailed 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.

Conditions

Healthy; Type 2 Diabetes; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Saline and Glucose

Study visit: Subjects will receive a caffeine free, standardized evening meal and remain fasting overnight. An IV infusion of saline and glucose (50%) will be given the next morning and continue until the end of study. Blood draws will be collected frequently from the IV line to monitor blood glucose levels.

Group Type: EXPERIMENTAL

Dextrose

Intervention Type: DRUG

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

Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Amino Acid and Glucose

Study visit: Subjects will receive a caffeine free, standardized evening meal and remain fasting overnight. An IV infusion of glucose (50%) will be given the next morning together with an IV infusion of Clinisol 15% (an amino acid mixture) will be given the next morning and continue until the end of study. Blood draws will be collected frequently from the IV line to monitor blood glucose levels.

Group Type: EXPERIMENTAL

Dextrose

Intervention Type: DRUG

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%

Intervention Type: DRUG

Intravenous infusion 0.003ml/kg/min infused from 0 to 240 minutes

Interventions

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

Intervention Type: DRUG

Clinisol 15%

Intravenous infusion 0.003ml/kg/min infused from 0 to 240 minutes

Intervention Type: DRUG

Other Intervention Names

Amino Acid Mixture

Eligibility Criteria

Inclusion Criteria

• 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.

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

• BMI ≤ 25 Kg/M^2).

Exclusion Criteria

• 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.

• 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.

• 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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Adrian Vella

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adrian Vella, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Jeanette Laugen

Role: primary

Laugen.Jeanette@mayo.edu

507-255-8110

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

R01DK116231

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22-000306

Identifier Type: -

Identifier Source: org_study_id