Glucagon Suppression by Hyperglycemia in the Presence and Absence of Amino Acid Infusion
- Conditions
- Type 2 DiabetesObesityHealthy
- Interventions
- Drug: Clinisol 15%
- Registration Number
- NCT05264727
- Lead Sponsor
- Mayo Clinic
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Amino Acid and Glucose Clinisol 15% 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. Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Saline and Glucose Dextrose 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. Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Amino Acid and Glucose Dextrose 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.
- Primary Outcome Measures
Name Time Method Change in Glucagon Suppression (G50) caused by amino acids vs. saline 240 minutes of study concentration of glucose necessary to suppress glucagon by 50%
- Secondary Outcome Measures
Name Time Method glucagon suppression (G50) is greater in obese compared to lean people without T2DM 240 minutes of study concentration of glucose necessary to suppress glucagon by 50%
Glucagon suppression (G50) is greater in people with T2DM 240 minutes of study concentration of glucose necessary to suppress glucagon by 50%
Trial Locations
- Locations (1)
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States