Understanding glucagon release in diabetes and obesity

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

This study tests how amino acids affect the release of glucagon and insulin in people with Type 2 Diabetes and obesity to see if there are differences between those who have diabetes and those who don't.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 25 Years to 65 Years
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Locations: 1 site (Rochester, Minnesota)
• Trial ID: NCT05264727 on ClinicalTrials.gov

What this trial studies

This study investigates how amino acids influence glucagon and insulin release in individuals with Type 2 Diabetes (T2DM) and obesity. It aims to determine the differences in glucagon secretion in response to amino acids between obese individuals with and without T2DM. Utilizing a novel population model of glucagon kinetics, the study will measure glucagon secretion and action, providing insights into α-cell function. The research will also assess how glucose infusions affect glucagon suppression in these populations.

Who should consider this trial

Good fit: Ideal candidates include obese individuals with Type 2 Diabetes and those without diabetes but with specific BMI criteria.

Not a fit: Patients with severe diabetes (HbA1c ≥ 8.5%) or those using insulin or other non-allowed medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of glucagon-related dysregulation in Type 2 Diabetes and obesity.

How similar studies have performed: Other studies have shown promise in understanding glucagon dynamics, but this approach is novel in its specific focus on amino acid effects in T2DM.

Eligibility criteria

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.

Where this trial is running

Rochester, Minnesota

• Mayo Clinic Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Adrian Vella, MD — Mayo Clinic

Conditions Healthy; Type 2 Diabetes; Obesity