Type 1 Diabetes Mellitus
Conditions
Keywords
Type 1 Diabetes Children Siblings HLA Genotyping Autoantibodies Islet Autoimmunity C-Peptide HbA1c Risk Factors Prospective Cohort Study
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.
Interventions
None listed
Sponsors
Privolzhsky Research Medical University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
4 Months to 29 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of a Prediction Model for Type 1 Diabetes in Healthy Siblings | Up to January 25, 2026 | Development of a prediction model for type 1 diabetes based on HLA class I and class II genotypes, diabetes-associated autoantibodies (IAA, GADA, IA-2A, ZnT8A, and ICA), C-peptide, glycated hemoglobin (HbA1c), and environmental risk factors in healthy siblings of children with type 1 diabetes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Development of Type 1 Diabetes in Healthy Siblings | October 2017 to January 25, 2026 | Occurrence of type 1 diabetes among healthy siblings during follow-up. |
| Diabetes-Associated Autoantibody Profile | Up to 3 years | Assessment of diabetes-associated autoantibodies (IAA, GADA, IA-2A, ZnT8A, and ICA) in children with type 1 diabetes and their healthy siblings. |
| HLA Class I and Class II Genotypes | Baseline | Assessment of HLA class I and class II genotypes associated with susceptibility to type 1 diabetes. |
| C-Peptide and Glycated Hemoglobin (HbA1c) | Up to 3 years | Assessment of endogenous insulin secretion and glycemic status using C-peptide and glycated hemoglobin measurements. |
Countries
Russia
Contacts
PRINCIPAL_INVESTIGATORKsenia Georgievna Korneva, MD, PhD
Privolzhsky Research Medical University, Nizhny Novgorod, Russia
STUDY_CHAIROlga Borisovna Bezlepkina, MD, DSc
National Medical Research Center for Endocrinology, Moscow, Russia
Outcome results
None listed