Type 1 Diabetes, Immunology, Genetics & Endogenous Insulin Production

NCT03490773 | Completed

• 3 other identifiers: CRF14214175613/SW/0312
• Study Type: observational
• Target: 287
• Locations: 2 countries
• Sites: 3

Brief Summary

Type I diabetes(T1D)T occurs when an individual loses the ability to make enough insulin to control their blood sugar levels. They need insulin injections to replace the insulin production that has been lost. Traditionally people with T1D are thought to make none of their own insulin after diagnosis, but we have recently identified that there are some people who have T1D but go one making insulin for many years. We would like to explore this in more depth and understand why some people with T1D go on making insulin and some do not. This will help us understand the causes of T1D and may help work out ways to protect this remaining insulin production, with improved blood sugar control, and reduced long-term complications of diabetes We aim to explore genetic and immunological factors which impact on the ability of an individual diagnosed with Type I diabetes (T1D) to produce their own insulin. We aim to study individuals who have been diagnosed with T1D with variable duration and assess the genetic and immunological profile of those whose are thought to be producing significant amounts of insulin despite a long duration and those who despite a very short duration, lose insulin production very quickly.

Conditions

Type 1 Diabetes Mellitus

Keywords

Cpeptide; Immunology

Outcome Measures

Primary Outcomes (1)

• Difference in immune function in Cpeptide negative and positive

  The frequency or suppressive function of regulatory T-cells and the frequency of auto reactive CD4 and CD8 T cells between C-peptide positive and C-peptide negative groups, (with patients and controls individually matched for age of diagnosis and duration).

  Within 6 months of last participant visit

Secondary Outcomes (1)

• Difference in HLA type in Cpeptide negative and positive groups

  Within 6 months of last participant visit

Eligibility Criteria

• Age: 5 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All potential participants will be identified from either routine clinical care or from existing research cohorts managed by the Peninsula Research Bank as part of the NIHR Exeter Clinical Research Facility (ECRF). Potential participants who appear to meet the entry criteria will be given written information on the project, followed by the opportunity to discuss the project in more detail with a member of the research team. The research team will be responsible for the recruitment process.

You may qualify if:

• Clinical diagnosis of Type 1 diabetes
• Insulin treated
• Known UCPCR status (positive/negative defined by UCPCR cut off of 0.2nmol/mmol)
• Age 5-65 years inclusive
• Able and willing to provide informed consent/assent

You may not qualify if:

• Pregnant or lactating (as this may limit blood sampling and affect T cell function)
• Any infectious illness within the last 2 weeks if it was a febrile illness, or within 2-3 days if it was non-febrile (as this may activate T cells non-specifically)
• Taking steroids or other immunosuppressive medications (as these may alter T cell function)
• Received any immunoglobulin treatments or blood products in the last 3 months (as these may alter T cell function)
• Any other medical condition which, in the opinion of the investigator, would affect the safety of the subject's participation.
• Recreational drug or alcohol abuse (excluding cannabis use more than 1 week prior to blood sampling) - drug abuse may alter T cell function.
• Severe complications of diabetes other than background retinopathy, uncomplicated neuropathy or proteinuria with creatinine in normal reference range (as more severe complications may affect T cell function)

Sponsors & Collaborators

• Royal Devon and Exeter NHS Foundation Trust: lead
• Leiden University Medical Center: collaborator
• King's College London: collaborator

Study Sites (3)

Leiden University Medical Center

Leiden, Netherlands

Location

Royal Devon & Exeter NHS Foundation Trust

Exeter, Devon, EX2 5DW, United Kingdom

Location

King's College London

London, SE1 9RT, United Kingdom

Location

Related Publications (6)

• Lawson JM, Tremble J, Dayan C, Beyan H, Leslie RD, Peakman M, Tree TI. Increased resistance to CD4+CD25hi regulatory T cell-mediated suppression in patients with type 1 diabetes. Clin Exp Immunol. 2008 Dec;154(3):353-9. doi: 10.1111/j.1365-2249.2008.03810.x.

  PMID: 19037920 BACKGROUND

• Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree TI. Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes. 2005 Jan;54(1):92-9. doi: 10.2337/diabetes.54.1.92.

  PMID: 15616015 BACKGROUND

• Hilbrands R, Huurman VA, Gillard P, Velthuis JH, De Waele M, Mathieu C, Kaufman L, Pipeleers-Marichal M, Ling Z, Movahedi B, Jacobs-Tulleneers-Thevissen D, Monbaliu D, Ysebaert D, Gorus FK, Roep BO, Pipeleers DG, Keymeulen B. Differences in baseline lymphocyte counts and autoreactivity are associated with differences in outcome of islet cell transplantation in type 1 diabetic patients. Diabetes. 2009 Oct;58(10):2267-76. doi: 10.2337/db09-0160. Epub 2009 Jul 14.

  PMID: 19602536 BACKGROUND

• Velthuis JH, Unger WW, Abreu JR, Duinkerken G, Franken K, Peakman M, Bakker AH, Reker-Hadrup S, Keymeulen B, Drijfhout JW, Schumacher TN, Roep BO. Simultaneous detection of circulating autoreactive CD8+ T-cells specific for different islet cell-associated epitopes using combinatorial MHC multimers. Diabetes. 2010 Jul;59(7):1721-30. doi: 10.2337/db09-1486. Epub 2010 Mar 31.

  PMID: 20357361 BACKGROUND

• Marren SM, Hammersley S, McDonald TJ, Shields BM, Knight BA, Hill A, Bolt R, Tree TI, Roep BO, Hattersley AT, Jones AG, Oram RA; TIGI consortium. Persistent C-peptide is associated with reduced hypoglycaemia but not HbA1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice? Diabet Med. 2019 Sep;36(9):1092-1099. doi: 10.1111/dme.13960. Epub 2019 Jun 27.

  PMID: 30955221 RESULT

• Shields BM, McDonald TJ, Oram R, Hill A, Hudson M, Leete P, Pearson ER, Richardson SJ, Morgan NG, Hattersley AT; TIGI Consortium. C-Peptide Decline in Type 1 Diabetes Has Two Phases: An Initial Exponential Fall and a Subsequent Stable Phase. Diabetes Care. 2018 Jul;41(7):1486-1492. doi: 10.2337/dc18-0465. Epub 2018 Jun 7.

  PMID: 29880650 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral Blood Mononuclear Cells (PBMCs) DNA Serum Plasma Urine

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Andrew Hattersley, Professor

  University of Exeter

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2018
• First Posted: April 6, 2018
• Study Start: November 1, 2014
• Primary Completion: March 31, 2021
• Study Completion: December 30, 2021
• Last Updated: June 23, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); GB (2)