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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: Mixed meal stimulated urinary C peptide for the assessment of residual beta cell function

• Study Type: Observational
• Enrollment (Actual): 17

Contacts and Locations

Study Locations

• United Kingdom
  • Avon
    • Bristol, Avon, United Kingdom, BS1 8HW
      • Joint Clinical Research Unit, UHBristol NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with Type 1 diabetes diagnosed in the last 5 years

Description

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

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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

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Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Stimulated urinary C peptide; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospitals Bristol and Weston NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: October 22, 2010
• First Submitted That Met QC Criteria: October 22, 2010
• First Posted (Estimate): October 25, 2010

Study Record Updates

• Last Update Posted (Estimate): January 7, 2016
• Last Update Submitted That Met QC Criteria: January 6, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Beta cell reserve, urinary C peptide
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: ME/2010/3452; 10/H0505/87 (Other Identifier: Berkshire REC)