Determinants of Glycaemic Control in Children With Type 1 Diabetes

NCT06325111 — Unknown, 800 participants, IRCCS Burlo Garofolo

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Exploring Genetic, Epigenetic and Environmental Determinants of Glycaemic Control in Children and Young Individuals With Type 1 Diabetes

Registry	NCT06325111
Status	Unknown
Study type	Observational
Enrollment	800 (Estimated)
Sponsor	IRCCS Burlo Garofolo (Other)
Conditions	Diabetes Mellitus, Type 1
Interventions	Determinants of T1D glycaemic control (Other)
Dates	start 2023-05-29, primary completion 2026-04-30 (estimated), completion 2026-04-30 (estimated), first posted 2024-03-22, last updated 2024-03-22
Locations	1 site in Italy

-Summary

Type 1 diabetes (T1D) is a common chronic disease of childhood associated with a significantly increased risk of micro- and macro-vascular complications, including neuropathy, nephropathy and cardiovascular diseases. The risk of development T1D comorbidities is associated with glycaemic control, a complex mechanism involving biological, physiological environmental factors.

While more than 60 genetic variants were already associated with Glycated hemoglobin (HbA1c) in healthy subjects, very few genes have been identified in T1D individuals. Also, hyperglycaemia could be the cause of epigenetic changes at specific target genes, such as DNA methylation, histone modifications and microRNAs, correlated to accelerated development of diabetes-related complications. Most recently, increasing evidence also suggested that human microbiome may play a crucial role in the onset and progression of T1D and dysbiosis of the gut and oral microbiota was reported as a typical feature of hyperglycaemia.

However, potential differences among poorly and good managed T1D subjects have not been still studied. Also, the exact mechanism by long-term hyperglycaemia's acts in T1D remains poorly understood. Therefore, this project will explore an emerging area of research by the study of possible genetic, epigenetic and environmental biomarkers among T1D subjects with different glycaemic control.

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+Arms and interventions

Arm	Type	Interventions	Description
Patients with T1D and optimal glycaemic control		Other: Determinants of T1D glycaemic control	Optimal glycaemic control will be defined as HbA1c values <7%
Patients with T1D and poor glycaemic control		Other: Determinants of T1D glycaemic control	Poor glycemic control will be defined as HbA1c value ≥7%

Determinants of T1D glycaemic control (Other): DNA genotyping, microbiome, DNA methylation and microRNAs analysis

+Outcome measures

Primary outcomes

Identification of genes involved in T1D glycaemic control [Through study completion, an average of 18 months]: DNA will be isolated from saliva by Genefix Saliva DNA/RNA collection kit (Isohelix, UK) and whole genome genotyping will be performed using Illumina chip arrays (CA, USA).
Identification of DNA methylation patterns involved in T1D glycaemic control [Through study completion, an average of 18 months]: Peripheral blood will be collected from each participant into EDTA-containing tubes and Genome-wide DNA methylation will be performed using the Illumina Infinium Human Methylation EPIC BeadChip array
Identification of microRNAs involved in T1D glycaemic control [Through study completion, an average of 18 months]: Peripheral blood will be collected from each participant into Ethylenediaminetetraacetic acid (EDTA)-containing tubes for microRNAs sequencing. Illumina TruSeq Small RNA Sample Preparation kit will be used for library preparation, and sequencing will be conducted by Illumina platform (CA, USA).
Identification of oral microbiome characteristics associated to T1D glycaemic control [Through study completion, an average of 18 months]: Bacterial DNA will be extracted from saliva and a 500 base pair region of the V1-V3 portion of the 16S ribosomal RNA gene as well as the 200 base pair region of the V3 portion will be amplified. The V3 amplicon will be used for template preparation and will be sequenced using the Ion PGM Hi-Q View sequencing kit (Life Technologies, New York, NY, USA) with the IonPGM™System technology

+Eligibility

Sex: All, ages: 6 Years to 20 Years

Inclusion Criteria:

* Type 1 diabetes subjects
* Age from 6 to 20 years old
* At least 5 years of duration of disease

Exclusion Criteria:

* Type 1 diabetes subjects incapable of giving valid informed consent or whose parents are incapable of giving valid informed consent.
* Type 1 diabetes subjects for whom it is not possible to collect information on the clinical history, starting from the onset of diabetes
* Subjects with other types of diabetes (i.e. type 2, monogenic diabetes, cystic fibrosis related diabetes)

+Locations (1)

Facility	City	Country	Status
Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"	Trieste	Italy	Recruiting