Clinical trial NCT06470295: Effect of C-peptide on Hypoglycemic Counterregulation
Official title: On the Regulation of Hepatic Glucose Metabolism During Insulin-induced Hypoglycemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Hypoglycemia
Type 1 Diabetes
Keywords: glucagon
hepatic glucose production
C-peptide
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2024-06-24
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each subject will undergo two metabolic studies, one where they receive an IV infusion of C-peptide during insulin-induced hypoglycemia, and one where they will receive an IV infusion of saline instead.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* BMI less than 30 kg/m2

Exclusion Criteria:

* pregnant or lactating women cigarette smoking presence of HIV or hepatitis presence of cardiovascular disease presence of microvascular disease

Primary outcomes:
measure: Glucagon
timeFrame: During procedure, up to 2.5 hours
measure: Hepatic glucose production
timeFrame: During procedure, up to 2.5 hours
measure: Glucose infusion rate
timeFrame: During procedure, up to 2.5 hours
Secondary outcomes:
measure: epinephrine
timeFrame: During procedure, up to 2.5 hours
measure: peripheral glucose uptake
timeFrame: During procedure, up to 2.5 hours
measure: cortisol
timeFrame: During procedure, up to 2.5 hours
measure: C-peptide
timeFrame: During procedure, up to 2.5 hours
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Jason Winnick, PhD
role: PRINCIPAL_INVESTIGATOR
References: