C-peptide for Low Blood Sugar

Overseen By Natalie Whitsett

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Cincinnati

Disqualifiers: Pregnancy, Smoking, HIV, Cardiovascular, others

Compensation: Varies

Number of Visits: 2

Duration: 2.5 hours per session

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether C-peptide, a natural protein, can boost glucagon levels and improve blood sugar management in people with type 1 diabetes during low blood sugar episodes. The study includes different groups: healthy individuals and those with type 1 diabetes, each receiving either C-peptide or a placebo (a substance with no active effect). The goal is to determine if C-peptide can help the liver produce more sugar when blood sugar levels drop too low. Individuals with type 1 diabetes and a BMI under 30, who do not have conditions like heart disease or smoking habits, might be suitable for this study. As an Early Phase 1 trial, this research focuses on understanding how C-peptide works in people, offering participants a chance to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that C-peptide is likely to be safe for humans?

Research has shown that C-peptide might help with low blood sugar caused by insulin by increasing glucagon levels, based on studies conducted on dogs. Detailed information from human studies is not yet available regarding its safety. The current study is in an early stage, with C-peptide still undergoing safety testing in people. However, as a natural protein in the body, C-peptide is generally considered safe. Existing data has not revealed any specific safety issues. Prospective trial participants might find this information reassuring, but discussing any concerns with trial organizers or a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about C-peptide for treating low blood sugar because it offers a novel approach compared to standard treatments like glucose tablets or glucagon injections. C-peptide, a peptide naturally produced in the body alongside insulin, may help stabilize blood sugar levels during insulin-induced hypoglycemia without the need for additional glucose intake. This treatment is particularly promising for people with Type 1 Diabetes (T1D), as it could provide a more physiological way to manage low blood sugar by enhancing the body's natural response. Unlike traditional treatments that only address immediate symptoms, C-peptide could offer longer-lasting regulation of blood sugar levels.

What evidence suggests that C-peptide might be an effective treatment for low blood sugar in type 1 diabetes?

Research has shown that C-peptide may help manage low blood sugar in people with type 1 diabetes. In studies with dogs, C-peptide increased the release of glucagon, a hormone that raises blood sugar, during insulin-induced low blood sugar episodes. This glucagon increase helped the liver produce more glucose, potentially preventing or reducing the severity of these episodes. Additionally, people with higher C-peptide levels often experience fewer severe low blood sugar incidents. In this trial, some participants with type 1 diabetes will receive C-peptide to evaluate its potential in improving blood sugar control by supporting the body's natural ability to regulate glucose. ^{1 4 5 6 7}

Who Is on the Research Team?

Jason Winnick, PhD

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

This trial is for individuals with type 1 diabetes who have a body mass index (BMI) under 30. It's not open to pregnant or breastfeeding women, smokers, or those with HIV, hepatitis, cardiovascular disease, or microvascular complications.

Inclusion Criteria

BMI less than 30 kg/m2

Exclusion Criteria

I have small blood vessel disease.

Pregnant or lactating women

Cigarette smoking

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-study Monitoring

Glycemic levels of T1D patients are monitored for 10 days prior to the main study to ensure no hypoglycemia occurs

10 days

Treatment

Participants undergo two hypoglycemic clamp studies with either C-peptide or saline infusion during insulin-induced hypoglycemia

2.5 hours per session

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• C-peptide

Trial Overview The study investigates whether C-peptide can help prevent severe low blood sugar in people with type 1 diabetes by increasing glucagon secretion and liver glucose production. Participants will receive either C-peptide or saline as a comparison.

How Is the Trial Designed?

Group I: Healthy Control- C-peptide Active Control 1 Intervention

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

Group II: T1D- C-peptide Active Control 1 Intervention

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

Group III: Healthy Control- Saline Placebo Group 1 Intervention

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

Group IV: T1D- Saline Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Published Research Related to This Trial

C-peptide, once thought to be biologically inactive, is now recognized for its role in initiating specific signaling pathways in various tissues, suggesting it has important physiological functions beyond insulin production.

C-peptide may help reverse harmful effects of high glucose levels in tissues like the kidneys and nerves, indicating its potential as a therapeutic agent for treating long-term complications associated with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological effects and therapeutic potential of proinsulin C-peptide. Yosten, GL., Maric-Bilkan, C., Luppi, P., et al.[2021]

C-peptide, when delivered in a complex with albumin and Zn2+, can significantly increase GLUT1 levels on red blood cell membranes, providing a potential alternative mechanism for glucose transport in type 1 diabetes patients.

This finding suggests that C-peptide may enhance glucose uptake in cells that are not directly responsive to insulin, potentially improving glucose management in individuals with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A C-peptide complex with albumin and Zn2+ increases measurable GLUT1 levels in membranes of human red blood cells. Geiger, M., Janes, T., Keshavarz, H., et al.[2021]

C-peptide, a byproduct of insulin production, is primarily cleared by the kidneys and can be measured in serum and urine to assess pancreatic B-cell function.

C-peptide testing is clinically useful for distinguishing between natural and injected insulin in patients, and it plays a crucial role in diabetes research by tracking B-cell secretion and evaluating the effects of different treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C-peptide. Hoekstra, JB., van Rijn, HJ., Erkelens, DW., et al.[2019]

C-peptide, a fragment of proinsulin, has been shown to have beneficial effects on various organs and tissues, including the kidneys and nervous system, particularly in the context of diabetes mellitus.

The C-peptide exerts its effects by binding to specific cell membrane receptors, activating signaling pathways that enhance protective mechanisms in cells, suggesting its potential as a therapeutic agent in diabetes-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Molecular mechanisms of action and physiological effects of the proinsulin C-peptide (a systematic review)]. Poteryaeva, ON., Usynin, IF.[2020]

In patients with type 1 diabetes, even modest levels of C-peptide, which indicate residual insulin secretion from beta cells, are linked to lower rates of diabetic complications such as retinopathy and nephropathy, based on a retrospective analysis of the Diabetes Control and Complications Trial involving multiple patient groups.

Sustained C-peptide secretion (greater than 0.20 nmol/l) significantly reduces the prevalence of severe hypoglycemia, highlighting the importance of maintaining some beta-cell function to improve safety in intensive diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Steffes, MW., Sibley, S., Jackson, M., et al.[2022]

In a study of 1180 adults with newly diagnosed diabetes, C-peptide levels were found to be significantly higher in non-autoimmune diabetes (Ab(-)) compared to autoimmune diabetes (Ab(+)), indicating its potential as a key biomarker for classification.

C-peptide was more effective than age and BMI in distinguishing between autoimmune and non-autoimmune diabetes, with a receiver operating characteristic (ROC) analysis showing the highest area under the curve (AUC) for C-peptide at 0.78.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levels of C-peptide, body mass index and age, and their usefulness in classification of diabetes in relation to autoimmunity, in adults with newly diagnosed diabetes in Kronoberg, Sweden. Thunander, M., Törn, C., Petersson, C., et al.[2021]

C-peptide, a byproduct of proinsulin, may help explain the long-term complications faced by patients with type 1 diabetes, highlighting its potential role in understanding diabetic complications.

The review discusses how C-peptide affects kidney function by influencing tubular Na,K-ATPase activity, suggesting specific molecular mechanisms that could be targeted for therapeutic interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physiological effects of C-peptide]. Tsimaratos, M.[2019]

C-peptide measurement is a valuable tool for assessing insulin secretion and can help classify diabetes subtypes and inform treatment options, but its use is often limited by practical challenges in blood sample collection.

Urine C-peptide measurement offers a noninvasive alternative that is reliable and stable, allowing for effective assessment of beta-cell function without the need for blood draws.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of C-Peptide in Urine as a Measure of Ongoing Beta Cell Function. McDonald, TJ., Perry, MH.[2022]

In a study of 1377 patients with type 2 diabetes mellitus (T2DM), those with fasting C-peptide levels between 1.71 and 2.51 ng/ml had the best glycaemic control and the lowest incidence of diabetic complications like diabetic kidney disease (DKD) and diabetic retinopathy (DR).

Higher levels of C-peptide were associated with improved chances of achieving glycaemic control, but excessive C-peptide may increase the risk of DKD while providing some protection against DR, indicating a complex role of C-peptide in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C-peptide, glycaemic control, and diabetic complications in type 2 diabetes mellitus: A real-world study. Huang, Y., Wang, Y., Liu, C., et al.[2022]

C-peptide, released alongside insulin, plays a crucial role in cellular signaling and has protective effects against complications from diabetes, but its effectiveness is influenced by the presence of insulin and glucose levels.

In experiments with HEK293 cells, C-peptide's ability to induce cellular responses was significantly reduced in the presence of insulin and varied with glucose concentration, suggesting that these factors must be carefully controlled in future studies and therapeutic developments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The actions of C-peptide in HEK293 cells are dependent upon insulin and extracellular glucose concentrations. Rossiter, JL., Redlinger, LJ., Kolar, GR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5446389/

A Practical Review of C-Peptide Testing in Diabetes - PMC C-peptide levels are associated with diabetes type and duration of disease. Specifically a c-peptide level of less than 0.2 nmol/l is associated ...

2. diabetesjournals.org diabetesjournals.org/diabetes/article/73/6/823/154235/Evidence-for-C-Peptide-as-a-Validated-Surrogate-to

Evidence for C-Peptide as a Validated Surrogate to Predict ... Participants with C-peptide levels of 30–200 pmol/L had about one-half the incidence of admissions for severe hypoglycemia and about two-thirds ...

3. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14785

C‐peptide determination in the diagnosis of type of diabetes ... Effect on C-peptide. Blood glucose concentrations. Low blood glucose may result in low C-peptide concentrations; When blood glucose >7.8 mmol/L ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1262363619300291

Glycaemic variability and hypoglycaemia are associated ... Patients with ≥ 1 episode of hypoglycaemia had significantly lower median C-peptide levels than patients without hypoglycaemia (274 (136–620) pmol/L vs. 675 ( ...

5. thelancet.com thelancet.com/journals/landia/article/PIIS2213-8587(23)00267-X/fulltext

C-peptide and metabolic outcomes in trials of disease ... C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06470295

Effect of C-peptide on Hypoglycemic Counterregulation We have observed that the naturally occurring protein C-peptide increases glucagon secretion in dogs during insulin-induced hypoglycemia, which increases ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4916002/

Correlation Between Hypoglycemia, Glycemic Variability ... Measures of glycemic variability and control, including rates of hypoglycemia, are significantly correlated with preservation of C-peptide.