Effect of C-peptide on Hypoglycemic Counterregulation
- Conditions
- Type 1 DiabetesHypoglycemia
- Interventions
- Other: Saline
- Registration Number
- NCT06470295
- Lead Sponsor
- University of Cincinnati
- Brief Summary
Iatrogenic hypoglycemia is the most prominent barrier to the safe, effective management of blood sugar in people with type 1 diabetes due to periodic over-insulinization. During insulin-induced hypoglycemia, glucagon secretion is diminished in type 1 diabetes which, in turn, reduces hepatic glucose production and increases the depth and duration of hypoglycemic episodes. We have observed that the naturally occurring protein C-peptide increases glucagon secretion in dogs during insulin-induced hypoglycemia, which increases hepatic glucose production; the experiments in this application will shed light on the translation of this finding to the human.
- Detailed Description
Iatrogenic hypoglycemia is recognized as a primary barrier to the safe, effective management of blood glucose in people with type 1 diabetes (T1D). In previous experiments in the dog, we observed that C-peptide infusion augmented glucagon secretion and hepatic glucose production during insulin-induced hypoglycemia. The proposed experiments will determine the translational impact of this finding in patients with and without T1D.
Specific Aim #1 is to determine, in healthy control subjects, the effect of C-peptide co-infusion with insulin on endogenous glucose production (EGP) and counterregulatory hormone levels during hypoglycemia. This will be addressed by studying a single group of healthy subjects two times. In both studies, hypoglycemia will be induced with an intravenous (IV) infusion of insulin. During one study, C-peptide will be infused during the hypoglycemic period, and in the other study, saline will be infused. EGP is our primary variable, with secondary analyses including counterregulatory hormones and metabolic substrates.
Specific Aim #2 is to determine, in T1D patients, the effect of C-peptide co-infusion with insulin on EGP and counterregulatory hormone levels during hypoglycemia. The research plan for this Aim is very similar to that of Aim #1, with the main exception being that we will study T1D patients instead of healthy controls (e.g., two hypoglycemic clamp studies where C-peptide is administered during one study and saline during the other). In addition, the glycemic levels of these T1D patients will be monitored for 10 days prior to this visit to ensure that they do not experience hypoglycemia which could confound the data for the metabolic studies. Similar to Aim #1, EGP is our primary outcome variable, with secondary analyses including hormone and substrate levels.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 38
- BMI less than 30 kg/m2
- pregnant or lactating women cigarette smoking presence of HIV or hepatitis presence of cardiovascular disease presence of microvascular disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Healthy Control- C-peptide C-peptide C-peptide will be infused in healthy control subjects during insulin-induced hypoglycemia T1D- C-peptide C-peptide C-peptide will be infused in T1D subjects during insulin-induced hypoglycemia Healthy Control- Saline Saline Saline will be infused in healthy control subjects during insulin-induced hypoglycemia T1D- Saline Saline Saline will be infused in T1D subjects during insulin-induced hypoglycemia
- Primary Outcome Measures
Name Time Method Hepatic glucose production During procedure, up to 2.5 hours from plasma
Glucagon During procedure, up to 2.5 hours from plasma
Glucose infusion rate During procedure, up to 2.5 hours Amount of glucose required to maintain glycemia at 55 mg/dL
- Secondary Outcome Measures
Name Time Method peripheral glucose uptake During procedure, up to 2.5 hours from plasma
cortisol During procedure, up to 2.5 hours from plasma
C-peptide During procedure, up to 2.5 hours from plasma
epinephrine During procedure, up to 2.5 hours from plasma
Trial Locations
- Locations (1)
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States