C-peptide for Low Blood Sugar

Overseen By Natalie Whitsett

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Cincinnati

Disqualifiers: Pregnancy, Smoking, HIV, Cardiovascular, others

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment C-peptide for low blood sugar?

Research shows that C-peptide, which is released with insulin, can help reduce severe low blood sugar episodes in people with diabetes by maintaining some insulin production. This suggests it might help manage low blood sugar by supporting the body's natural insulin production. ^{1 2 3 4 5}

Is C-peptide safe for humans?

C-peptide, a part of insulin, has shown positive effects on organs like the kidneys and heart, and may help with diabetes complications. It is generally considered safe, but its effects depend on insulin and glucose levels. ^{3 6 7 8 9}

How does the drug C-peptide differ from other treatments for low blood sugar?

C-peptide is unique because it is a naturally occurring peptide released with insulin and can bind to cell membranes, initiating specific signaling pathways. Unlike traditional treatments that focus on insulin replacement, C-peptide may offer additional benefits by reversing damage caused by high glucose levels in tissues like the kidneys and nerves, and it can be measured noninvasively through urine tests. ^{2 5 6 7 10}

Research Team

Jason Winnick, PhD

Principal Investigator

University of Cincinnati

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• C-peptide (Hormone Therapy)

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.

Participant Groups

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+

Findings from Research

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 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 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 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 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, 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

C-peptide, glycaemic control, and diabetic complications in type 2 diabetes mellitus: A real-world study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Detection of C-Peptide in Urine as a Measure of Ongoing Beta Cell Function. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. [2022]

4. England 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

C-peptide. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Physiological effects of C-peptide]. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Physiological effects and therapeutic potential of proinsulin C-peptide. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

The actions of C-peptide in HEK293 cells are dependent upon insulin and extracellular glucose concentrations. [2022]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

A C-peptide complex with albumin and Zn2+ increases measurable GLUT1 levels in membranes of human red blood cells. [2021]