Prospective Cohort Study of Genetic, Immunologic, and Environmental Risk Factors for Type 1 Diabetes in Children and Their Healthy Siblings
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 1,034
- Locations
- 1
Study Overview
Brief Summary
This prospective observational cohort study evaluated genetic, immunologic, and environmental factors associated with type 1 diabetes in children. Children with newly diagnosed type 1 diabetes and their healthy siblings were enrolled between October 2017 and June 2021. Data collection included HLA class I and class II genotyping, measurement of diabetes-associated autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), zinc transporter 8 (ZnT8A), and islet cell antibodies (ICA), as well as C-peptide and glycated hemoglobin (HbA1c). Healthy siblings underwent annual follow-up assessments for three years, while children with type 1 diabetes were evaluated every three months during the first year after diagnosis. Information on environmental risk factors was collected using an investigator-developed questionnaire based on anamnestic data. The study aimed to identify biomarkers and risk factors associated with the development and progression of type 1 diabetes in children.
Detailed Description
Type 1 diabetes is a chronic autoimmune disease resulting from immune-mediated destruction of pancreatic beta cells. Genetic susceptibility, autoimmune processes, and environmental exposures are believed to contribute to disease development and progression.
This prospective observational cohort study included children with newly diagnosed type 1 diabetes and their healthy siblings. Participants were enrolled between October 2017 and June 2021. Baseline assessment included HLA class I and class II genotyping, measurement of diabetes-associated autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), zinc transporter 8 (ZnT8A), and islet cell antibodies (ICA), as well as C-peptide and glycated hemoglobin (HbA1c).
Children with type 1 diabetes underwent follow-up clinical and laboratory assessments every three months during the first year after diagnosis. Healthy siblings underwent annual follow-up assessments for three years, including repeated evaluation of diabetes-associated autoantibodies, C-peptide, and glycated hemoglobin. HLA genotyping was performed only at baseline.
Parents completed an investigator-developed questionnaire designed to collect anamnestic information on environmental risk factors for type 1 diabetes identified in the scientific literature. The questionnaire included data on prenatal and perinatal history, infant feeding practices, infectious diseases, family history, and other environmental exposures potentially associated with type 1 diabetes risk.
Follow-up of healthy siblings continued until January 25, 2026, through telephone contact to determine whether type 1 diabetes had developed during the observation period. The collected data were used to evaluate associations among genetic, immunologic, laboratory, and environmental factors and to identify biomarkers associated with the risk and progression of type 1 diabetes in children.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 4 Months to 29 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •For children with newly diagnosed type 1 diabetes:
- •Age 0 to 17 years, inclusive; Diagnosis of type 1 diabetes mellitus established according to World Health Organization (WHO) diagnostic criteria applicable during the study period.
- •For healthy siblings:
- •Biological brothers or sisters of a participant with type 1 diabetes mellitus; Absence of laboratory criteria for type 1 diabetes at enrollment, including blood glucose and glycated hemoglobin (HbA1c) values below diagnostic thresholds for type 1 diabetes.
- •For all participants:
- •Written informed consent obtained from parents or legal guardians prior to study enrollment.
Exclusion Criteria
- •Monogenic diabetes mellitus; Secondary diabetes mellitus; Refusal or withdrawal of informed consent.
Investigators
Anastasia E. Bolshakova
Associate Professor
Privolzhsky Research Medical University