Overseen ByJason Winnick, PhD
Age: 18 - 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Cincinnati
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.
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.
13568What 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.
12469Is 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.
235710Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications.
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.Exclusion Criteria
I have hepatitis.
I am HIV positive.
I have a heart condition.
I have small blood vessel disease.
Participant Groups
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.
4Treatment groups
Active Control
Placebo Group
Group I: Healthy Control- C-peptideActive Control1 Intervention
C-peptide will be infused in healthy control subjects during insulin-induced hypoglycemia
Group II: T1D- C-peptideActive Control1 Intervention
C-peptide will be infused in T1D subjects during insulin-induced hypoglycemia
Group III: Healthy Control- SalinePlacebo Group1 Intervention
Saline will be infused in healthy control subjects during insulin-induced hypoglycemia
Group IV: T1D- SalinePlacebo Group1 Intervention
Saline will be infused in T1D subjects during insulin-induced hypoglycemia
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of CincinnatiCincinnati, OH
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Who is running the clinical trial?
University of CincinnatiLead Sponsor
References
C-peptide. [2019]C-peptide is a polypeptide originating from proinsulin after its cleavage in the B-cell. It is secreted equimolarly with the other cleavage product, insulin, into the portal circulation. Only a minimal fraction of C-peptide is extracted by the liver; it is supposed to be mainly removed by the kidney. A small, constant proportion is excreted in the urine. C-peptide is measured in serum and urine by radioimmunoassay. The major sources of error of the assay are related to standard, tracer, antiserum specificity and reactivity with proinsulin, and to degradation of C-peptide. Many secretagogues are used to evaluate the B-cell function, of which glucagon is the most simple. Clinical applications of C-peptide include differentiating between endogenous and exogenous hyperinsulinism and establishing the need of insulin therapy in diabetic patients already treated with insulin. The primary value of C-peptide, however, is in clinical research, where it offers a unique opportunity to follow the B-cell secretion in diabetic subjects and to evaluate the difference that various factors may exert on its activity.
Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. [2022]In patients with type 1 diabetes, measurement of connecting peptide (C-peptide), cosecreted with insulin from the islets of Langerhans, permits estimation of remaining beta-cell secretion of insulin. In this retrospective analysis to distinguish the incremental benefits of residual beta-cell activity in type 1 diabetes, stimulated (90 min following ingestion of a mixed meal) C-peptide levels at entry in the Diabetes Control and Complications Trial (DCCT) were related to measures of diabetic retinopathy and nephropathy and to incidents of severe hypoglycemia. Based on the analytical sensitivity of the assay (0.03 nmol/l) and study entry criteria, the DCCT subjects were divided into four groups of stimulated C-peptide responses: 40 mg/24 h once and repeated at the next annual visit). There were also differences in severe hypoglycemia across C-peptide levels in both treatment groups. In the intensively treated cohort there were essentially identical prevalences of severe hypoglycemia ( approximately 65% of participants) in the first three groups; however, those subjects with mixed-meal stimulated C-peptide level >0.20 nmol/l for at least baseline and the first annual visit in the DCCT experienced a reduced prevalence of approximately 30%. Therefore, even modest levels of beta-cell activity at entry in the DCCT were associated with reduced incidences of retinopathy and nephropathy. Also, continuing C-peptide (insulin) secretion is important in avoiding hypoglycemia (the major complication of intensive diabetic therapy).
[Physiological effects of C-peptide]. [2019]Connecting peptide (C-peptide) is a product of proinsulin cleavage. New findings demonstrate, that it may serve to understand the mechanisms involved in the development of long-term complications in type 1 diabetic patients. The present review focuses on: 1. Making a point about C-peptide-induced tubular effects on the basis of clinical and experimental experiments, 2. Precising the molecular mechanisms involved in C-peptide-induced tubular Na,K-ATPase effects.
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]C-peptide is a main outcome measure in treatment trials of diabetes. C-peptide also has a role in the classification of diabetes, which is often difficult in adults and this is also increasingly recognised in adolescents and elders.
Physiological effects and therapeutic potential of proinsulin C-peptide. [2021]Connecting Peptide, or C-peptide, is a product of the insulin prohormone, and is released with and in amounts equimolar to those of insulin. While it was once thought that C-peptide was biologically inert and had little biological significance beyond its role in the proper folding of insulin, it is now known that C-peptide binds specifically to the cell membranes of a variety of tissues and initiates specific intracellular signaling cascades that are pertussis toxin sensitive. Although it is now clear that C-peptide is a biologically active molecule, controversy still remains as to the physiological significance of the peptide. Interestingly, C-peptide appears to reverse the deleterious effects of high glucose in some tissues, including the kidney, the peripheral nerves, and the vasculature. C-peptide is thus a potential therapeutic agent for the treatment of diabetes-associated long-term complications. This review addresses the possible physiologically relevant roles of C-peptide in both normal and disease states and discusses the effects of the peptide on sensory nerve, renal, and vascular function. Furthermore, we highlight the intracellular effects of the peptide and present novel strategies for the determination of the C-peptide receptor(s). Finally, a hypothesis is offered concerning the relationship between C-peptide and the development of microvascular complications of diabetes.
Detection of C-Peptide in Urine as a Measure of Ongoing Beta Cell Function. [2022]C-peptide is a protein secreted by the pancreatic beta cells in equimolar quantities with insulin, following the cleavage of proinsulin into insulin. Measurement of C-peptide is used as a surrogate marker of endogenous insulin secretory capacity. Assessing C-peptide levels can be useful in classifying the subtype of diabetes as well as assessing potential treatment choices in the management of diabetes.Standard measures of C-peptide involve blood samples collected either fasted or, most often, after a fixed stimulus (such as oral glucose, mixed meal, or IV glucagon). Despite the established clinical utility of blood C-peptide measurement, its widespread use is limited. In many instances this is due to perceived practical restrictions associated with sample collection.Urine C-peptide measurement is an attractive noninvasive alternative to blood measures of beta-cell function. Urine C-peptide creatinine ratio measured in a single post stimulated sample has been shown to be a robust, reproducible measure of endogenous C-peptide which is stable for three days at room temperature when collected in boric acid. Modern high sensitivity immunoassay technologies have facilitated measurement of C-peptide down to single picomolar concentrations.
[Molecular mechanisms of action and physiological effects of the proinsulin C-peptide (a systematic review)]. [2020]The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new information has appeared on the physiological effects of the C-peptide, indicating its positive effect on many organs and tissues, including the kidneys, nervous system, heart, vascular endothelium and blood microcirculation. Studies on experimental models of diabetes mellitus in animals, as well as clinical trials in patients with diabetes, have shown that the C-peptide has an important regulatory effect on the early stages of functional and structural disorders caused by this disease. The C-peptide exhibits its effects through binding to a specific receptor on the cell membrane and activation of downstream signaling pathways. Intracellular signaling involves G-proteins and Ca2+-dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+/K+-ATPase and important transcription factors involved in apoptosis, anti-inflammatory and other intracellular defense mechanisms. This review gives an idea of the C-peptide as a bioactive endogenous peptide that has its own biological activity and therapeutic potential.
A C-peptide complex with albumin and Zn2+ increases measurable GLUT1 levels in membranes of human red blood cells. [2021]People with type 1 diabetes (T1D) require exogenous administration of insulin, which stimulates the translocation of the GLUT4 glucose transporter to cell membranes. However, most bloodstream cells contain GLUT1 and are not directly affected by insulin. Here, we report that C-peptide, the 31-amino acid peptide secreted in equal amounts with insulin in vivo, is part of a 3-component complex that affects red blood cell (RBC) membranes. Multiple techniques were used to demonstrate saturable and specific C-peptide binding to RBCs when delivered as part of a complex with albumin. Importantly, when the complex also included Zn2+, a significant increase in cell membrane GLUT1 was measured, thus providing a cellular effect similar to insulin, but on a transporter on which insulin has no effect.
C-peptide, glycaemic control, and diabetic complications in type 2 diabetes mellitus: A real-world study. [2022]To explore the relationship between C-peptide and glycaemic control rate and diabetic complications (microvascular complication and cerebral infarction) and provide evidence for stratified treatment of type 2 diabetes mellitus (T2DM)-based C-peptide.
The actions of C-peptide in HEK293 cells are dependent upon insulin and extracellular glucose concentrations. [2022]Connecting peptide, or C-peptide, is a part of the insulin prohormone and is essential for the proper folding and processing of the mature insulin peptide. C-peptide is released from the same beta cell secretory granules as insulin in equimolar amounts. However, due to their relative stabilities in plasma, the two peptides are detected in the circulation at ratios of approximately 4:1 to 6:1 (C-peptide to insulin), depending on metabolic state. C-peptide binds specifically to human cell membranes and induces intracellular signaling cascades, likely through an interaction with the G protein coupled receptor, GPR146. C-peptide has been shown to exert protective effects against the vascular, renal, and ocular complications of diabetes. The effects of C-peptide appear to be dependent upon the presence of insulin and the absolute, extracellular concentration of glucose. In this study, we employed HEK293 cells to further examine the interactive effects of C-peptide, insulin, and glucose on cell signaling. We observed that C-peptide's cellular effects are dampened significantly when cells are exposed to physiologically relevant concentrations of both insulin and C-peptide. Likewise, the actions of C-peptide on cFos and GPR146 mRNA expressions were affected by changes in extracellular glucose concentration. In particular, C-peptide induced significant elevations in cFos expression in the setting of high (25 mmol) extracellular glucose concentration. These data indicate that future experimentation on the actions of C-peptide should control for the presence or absence of insulin and the concentration of glucose. Furthermore, these findings should be considered prior to the development of C-peptide-based therapeutics for the treatment of diabetes-associated complications.