Effect of Glucagon on Fasting Insulin Secretion and Glucose Metabolism in Subjects Without Type 2 Diabetes
- Conditions
- PreDiabetes
- Interventions
- Other: GlucagonOther: Glucose
- Registration Number
- NCT06424106
- Lead Sponsor
- Mayo Clinic
- Brief Summary
Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.
- Detailed Description
The interaction between α-cell and β-cell function to regulate fasting glucose is incompletely understood. This is an important gap in our knowledge as fasting glucose contributes disproportionately to HbA1c and the microvascular complications of type 2 diabetes (T2DM). The regulation of fasting glucose in health and disease is relatively understudied.
Insulin and glucagon should regulate glucose reciprocally through direct interaction; insulin restrains α-cell secretion while glucagon directly stimulates β-cell secretion. In addition, there are indirect interactions via changes in glucose. Glucagon increases endogenous glucose production (EGP) increasing glucose (and insulin secretion). Conversely, insulin stimulates glucose disappearance (Rd) and suppresses EGP, lowering glucose (and stimulating glucagon).
However, this does not appear to occur uniformly in prediabetes. For example, in impaired fasting glucose (IFG), glucagon secretion rate (GSR) is inappropriate for the prevailing glucose. This is not accompanied by reciprocal changes in insulin secretion rate (ISR). Variability in the hepatic response to glucagon and to insulin further compound the dysregulation of fasting glucose. The net effect of these variables is unknown. This experiment is intended to test the hypothesis that impaired glucagon-induced insulin secretion contributes to fasting hyperglycemia in IFG.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Individuals with normal or impaired fasting glucose and normal or impaired glucose tolerance
- HbA1c less than 6.5%
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Glucagon Infusion Glucagon A glucagon infusion (0.2 ng/kg/min) will start at 0900 (0 min), increasing to 0.4 (1000), 0.6 (1100) and 0.8 ng/kg/min (1200) at 60-minute intervals - ending at 1300 (240 min). Glucose Infusion Glucose At 0900 (0 min) a glucose infusion will commence, and the infusion rate varied to replicate (± 5mg/dL) that individual's glucose concentrations observed during the Glucagon Infusion Day. The experiment will end at 1300 (240 min) when infusions are stopped.
- Primary Outcome Measures
Name Time Method Change in beta-cell responsivity induced by glucagon Beta-cell responsivity will be calculated as the gradient of the relationship between glucose concentrations and insulin secretion rate during the study day over the 4 hours (0 to 240 minutes) of the study The beta-cell responsivity observed during glucagon infusion will be compared to that observed during glucose infusion
- Secondary Outcome Measures
Name Time Method change in endogenous glucose production induced by glucagon The rate of endogenous glucose production at the end of the study (240 minutes) will be expressed as a percentage of that at the beginning of the study (0 minutes). The % change for each study day will then be compared The endogenous glucose production observed during glucagon infusion will be compared to that observed during glucose infusion
change in glucose disappearance induced by glucagon The rate of glucose disappearance at the end of the study (240 minutes) will be expressed as a percentage of that at the beginning of the study (0 minutes). The % change for each study day will then be compared The glucose disappearance observed during glucagon infusion will be compared to that observed during glucose infusion
Trial Locations
- Locations (1)
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States