Brief Summary

Type 1 diabetes (T1D) results from destruction of insulin-producing beta cells in the pancreas by the body's own immune system (autoimmunity). It is not fully understood what causes this type of diabetes and why there is variation in age of onset and severity between people who develop the disease. The aim of this work is to study very unusual people who develop T1D extremely young, as babies under 2 years of age (EET1D). The investigators think that, for the condition to have developed that early, they must have an unusual or extreme form of autoimmunity. Studying people with EET1D will enable us to look at exactly what goes wrong with the immune system because they have one of the most extreme forms of the disease. Much may be learned about the disease from a small number of rare individuals. The investigators aim to confirm that they have autoimmune type 1 diabetes and then try to understand how they have developed diabetes so young by studying their immune system genes, the function of their immune system, and environmental factors (such as maternal genetics) that may play a role in their development of the disease. People with diabetes diagnosed under 12 months are very rare, live all over the world. and are usually referred to Exeter for genetic testing. Individuals will be contacted via their clinician to ask for more information about their diabetes and their family history. Samples will be collected to study whether they still make any of their own insulin and whether they make specific antibodies against their beta cells in the pancreas. Separately, their immune system will be studied in depth using immune cells isolated from a blood sample. These cells will undergo cutting edge techniques by Dr Tim Tree at King's College London, by Professor Bart Roep at Leiden University Medical Center, Netherlands, and Dr Cate Speake, Benaroya Research Institute, Seattle (USA). Some of these tests have never been used in people of young ages around the world, so an aim of this project will be to develop methods that can be used to study people even if they live far away. Additional funding extended the study for a further 3 years (Phase 2) to include recruitment of infants without diabetes, aged 0-6 years, as controls to enable assessment of how the abnormalities found in autoimmune and non-autoimmune diabetes compare to normal early life development of the immune system. An additional funding award extended the study (Phase 3) until November 2028, to advance the EXE-T1D program into its third phase, building on major discoveries from phases 1 and 2 to identify, validate, and target immune pathways that drive extremely early-onset type 1 diabetes (eeT1D) and are likely relevant to T1D across all ages. eeT1D cases, diagnosed within the first two years of life, represent particularly aggressive onset of beta-cell autoimmunity. They offer a unique lens to uncover mechanisms of immune dysregulation, informed by both polygenic and monogenic causes. The central aim is to move from pathway discovery to demonstration of novel druggable targets with potential to delay or prevent T1D onset across all ages.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

300

participants targeted

Target at P75+ for all trials

Timeline

31mo left

Started Sep 2017

Longer than P75 for all trials

Geographic Reach

3 countries

4 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

11.2 years study duration

Study Progress77%

Sep 2017Nov 2028

Study Start

First participant enrolled

September 19, 2017

Completed

2 months until next milestone

First Submitted

Initial submission to the registry

November 16, 2017

Completed

26 days until next milestone

First Posted

Study publicly available on registry

December 12, 2017

Completed

10.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2028

Expected

1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2028

Last Updated

December 19, 2025

Status Verified

December 1, 2025

Enrollment Period

11.1 years

First QC Date

November 16, 2017

Last Update Submit

December 12, 2025

Conditions

Type1 Diabetes Mellitus

Keywords

type 1 diabetesmonogenic diabetesautoimmune diabetesearly-onset autoimmune diabetesbeta cell (β-cell) destructiontype 1 diabetes genetic riskextremely early-onset Type 1 diabetesneonatal diabetes

Outcome Measures

Primary Outcomes (1)

Measure beta cell function in EET1D compared to T1D, NDM and non-diabetic controls.
C-peptide and GAD, IA2, ZnT8 autoantibody measurement
Within 12 months of last participant's final visit.

Secondary Outcomes (3)

Immune phenotyping in EET1D compared to T1D, NDM and non-diabetic controls.
Within 12 months of last participant's final visit.
Difference in immune gene expression
Within 12 months of last participant's final visit.
Association of maternal and paternal non-inherited HLA alleles with EET1D
Within 12 months of last participant's final visit.

Study Arms (5)

Study 1: Existing EET1D (Case)

* Aged 0 to 70 years * Clinical diagnosis of diabetes \<24 months (+ evidence of WHO diabetes criteria) * Negative genetic test for mutations causing non-autoimmune neonatal diabetes if diagnosed \<12 months * Type 1 diabetes genetic risk score \>50th centile of T1D reference group, or monogenic cause of T1D (e.g. STAT3 or FOXP3 mutation).