EXtremely Early-onset Type 1 Diabetes EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)

Launched by UNIVERSITY OF EXETER · Dec 10, 2017

Keywords

ClinConnect Summary

The EXtremely Early-onset Type 1 Diabetes study aims to understand why some babies develop type 1 diabetes before they even turn 2 years old. This form of diabetes happens when the body's immune system mistakenly attacks the insulin-producing cells in the pancreas. By studying these very young patients, researchers hope to learn more about how and why this happens, focusing on their immune system, genetics, and possible environmental factors that could contribute to the disease. The study will also include infants without diabetes to compare how their immune systems develop normally.

To participate in the study, individuals must be diagnosed with type 1 diabetes before the age of 24 months, or be between 0 to 6 years old without diabetes. Participants can expect to provide blood samples for various tests that investigate their immune function and genetic background. This research is crucial because it may help uncover new insights into type 1 diabetes and improve understanding of this rare condition, ultimately benefiting future patients. If you or someone you know might be eligible, your healthcare provider will reach out for more information.

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Eligibility criteria

• Inclusion Criteria:
• Study 1:
• • EET1D
• • 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.
• • T1D Controls
• • Age 0-70 years (matched to above)
• • Clinical diagnosis of T1D (diagnosed age 1-20 years)
• • Insulin treated from diagnosis.
• • Monogenic / NDM controls
• • Diagnosis of diabetes \<12 months
• • Diagnosis of monogenic / NDM (confirmed by Exeter Molecular Genetics Laboratory).
• Study 2:
• • EET1D
• • Aged 0 to 24 months at recruitment
• • Clinical diagnosis of diabetes \<24 months (+ evidence of WHO diabetes criteria)
• • Negative genetic test for mutations causing non-autoimmune neonatal diabetes
• • Type 1 diabetes genetic risk score \>50th centile of T1D reference group, or monogenic cause of T1D.
• • Monogenic/NDM controls
• • Diagnosis of diabetes \<24 months
• • Age 0 to 18 months at recruitment
• • Diagnosis of monogenic/NDM (confirmed by Exeter Molecular Genetics Laboratory).
• • Non-diabetic controls
• • Aged 0-6 years
• • Attending specified participating hospital sites for elective surgery, including but not limited to: inguinal hernia repair, umbilical/midline hernia repair, orchidopexy, gastrostomy insertion/change, hypospadias repair, cleft palate repair, excision of accessory digit, laryngoscopy, adenoidectomy, tonsillectomy, MRI under general anaesthesia, eye surgery.
• Exclusion Criteria:
• Study 1:
• • Aged \>70 years
• • No diagnosis of diabetes
• • MODY (e.g. caused by HNF1A/HNF4A/HNF1B/GCK mutations), type 2 diabetes or diabetes related to pancreatic insufficiency or syndromic diabetes
• • Intercurrent illness at time of sampling for PBMCs (see below).
• Study 2:
• • Aged \>24 months
• • Clinical diagnosis of diabetes \>24 months
• • Intercurrent illness at time of sampling for PBMCs or RNA (see below).
• Non-diabetic controls:
• • Aged \>6 years
• • Diagnosis of diabetes or other autoimmune condition
• • Known immunological disorder
• • On immunosuppressive medication
• • Ongoing infections/sepsis
• • Major congenital abnormality or significant systemic illness that may affect the immune system, e.g. metabolic disease, 22q deletion syndrome
• • Recent (within two weeks) febrile illness
• • Renal failure.
• • For PBMC and RNA sampling: Exclusion for factors that may alter T cell function and RNAseq
• Review the following exclusion criteria carefully at time of appointment as some details may have changed since initial contact:
• • Recreational drug use (excluding cannabis use more than 1 week prior to blood sampling) - drug abuse may alter T cell function
• • Alcohol related illness (excessive alcohol consumption may alter T cell function)
• • Renal failure: Creatinine \>200 (as 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.
• Factors that if temporary would lead to rearrangement of study visit but if long duration, may lead to exclusion subject to the CI's discretion:
• • 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).