Effect of C-peptide on Hypoglycemic Counterregulation

University of Cincinnati

Status and phase: Enrolling; Early Phase 1

Conditions: Hypoglycemia; Type 1 Diabetes

Treatments: Biological: C-peptide; Other: Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT06470295

2022-0236

Details and patient eligibility

About

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.

Full 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.

Enrollment: 38 estimated patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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38 participants in 4 patient groups, including a placebo group

Healthy Control- Saline

Placebo Comparator group

Description:

Saline will be infused in healthy control subjects during insulin-induced hypoglycemia

Treatment:

Other: Saline

Healthy Control- C-peptide

Active Comparator group

Description:

C-peptide will be infused in healthy control subjects during insulin-induced hypoglycemia

Treatment:

Biological: C-peptide

T1D- Saline

Placebo Comparator group

Description:

Saline will be infused in T1D subjects during insulin-induced hypoglycemia

Treatment:

Other: Saline

T1D- C-peptide

Active Comparator group

Description:

C-peptide will be infused in T1D subjects during insulin-induced hypoglycemia

Treatment:

Biological: C-peptide