Towards Simple and Non-invasive Assessment of Residual Beta-cell Function in Type 1 Diabetes

Study Overview
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Brief Summary
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Type 1 diabetes is condition in which progressive autoimmune destruction of insulin-producing beta-cells leads to absolute insulin deficiency. At the time of clinical presentation, it is estimated that 50-80% of beta-cell function has been lost. Good glycaemic control from diagnosis has been shown to preserve beta-cell function. The recent identification of immuno-interventions able to reduce autoimmune destruction and preserve beta-cell function has lead to an increased urgency to develop such tools. With mixed-meal stimulated serum C-peptide being a gold standard, there are currently no tests that are suited for use in clinical practice to detect and monitor residual beta cell function. There is a therefore a need for a test that is sufficiently sensitive to assess beta cell function reserve in Type 1 diabetes for clinical practice purposes, which will be simple, reproducible and suitable for use even in the non-observed setting. Using mixed meal stimulation of plasma C-peptide (stable by-product in insulin secretion that reliably reflects insulin production) response as a reference, we propose to compare mixed meal stimulated urinary C-peptide as potential candidate for this application. This is a pilot investigation in which a sample of 30 participants will be recruited. It is anticipated that the current project will identify a simple method for analysing beta cell reserve in Type 1 diabetes. This will then be applied to screening clinic populations of recently diagnosed patients with type 1 diabetes. The aim will be to identify subjects who may be suitable for early intensified insulin regimes (e.g. insulin pump therapy) and novel immuno-intervention strategies designed to preserve residual beta cell function and improve long-term outcomes. Currently such immunointervention has been reserved for subjects within 3 months of diagnosis only, excluding a significant number of subjects who may potentially benefit.

Official Title
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Towards Simple and Non-invasive Assessment of Residual Beta-cell Function in Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Other: Mixed meal stimulated urinary C peptide for the assessment of residual beta cell function


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:1. 1. Type 1 diabetes diagnosed in the last 5 years 2. Age 18-45 years 3. BMI between 18.5 and 29.9 4. Insulin requirement less than 0.8 units/kg - Exclusion Criteria: 1. HbA1c higher than 10% 2. Ongoing steroid treatment or chemotherapy 3. Pregnancy and breast feeding 4. eGFR less than 50ml/min/1.73m2 -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Stimulated urinary C peptide<br>Study will be designed to assess stimulated urinary C-peptide in comparison to mixed-meal stimulated plasma C-peptide response in the same individual in 30 number of patients with Type 1 diabetes. | Other: Mixed meal stimulated urinary C peptide for the assessment of residual beta cell function<br>* Study will be designed to assess stimulated urinary C-peptide in comparison to mixed-meal stimulated plasma C-peptide response in the same individual in 30 number of patients with Type 1 diabetes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of whether two-hour urinary C-peptide response to mixed-meal (measured as area under the curve on the graph) can be used assess residual beta-cell function in the first 5 years after diagnosis of Type 1 diabetes. |  | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare fasting urinary C-peptide to plasma C-peptide response to mixed-meal |  | One year | 
| To compare urinary C-peptide response to mixed meal in each hour post stimulation to plasma C-peptide response to mixed-meal |  | One year | 
| To compare total four-hour urinary C-peptide (area under the curve) response to mixed meal to plasma C-peptide response to mixed-meal |  | One year | 
| To assess whether urinary C-peptide response to mixed-meal is reproducible in non-observed setting. |  | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta cell reserve, urinary C peptide