Background: Several studies have shown that type 1 diabetes mellitus (T1DM) may contribute to the early onset or acceleration of cognitive impairment (intelligence, psychomotor efficiency, information management speed, visual attention, visual perception and cognitive flexibility). Tear proteomics seems to provide useful information for understanding the molecular mechanisms of various ocular and systemic diseases.
Objective and Hypotheses: The purpose of this prospective study was to identify the proteomic profile in tear samples in children and adolescents with T1DM that are followed at the Diabetes Center of the First Department of Pediatrics of the National and Kapodistrian University of Athens, at "Aghia Sophia" Children's Hospital, and to correlate with the level of cognitive functions of these patients.
Methods and Results: Seventy children and adolescents, aged 6-17 years, with T1DM and seventy healthy age- and gender-matched children and adolescents were recruited by recording clinical and laboratory data (glycosylated hemoglobin, high sensitivity CRP, IL-6, TNF-α, BDNF, salivary amylase and lipidogram). The assessment of the level of cognitive functions were performed using the Wechsler Intelligence Scale for Children (WISC-V), Achenbach and Stroop. Tear sampling was performed with Schirmer strips. The tear proteins were isolated and trypsinised, and then peptides were separated by high performance liquid chromatography. The identification and quantification of the peptides and therefore the corresponding proteins were achieved using a Q Exactive HF mass spectrometer. The results of the bioinformatics analysis of the differentially expressed proteins and the results of the psychometric tools were combined with the clinical and laboratory parameters of the patients in order to identify and use biomarkers in tears that will show an increased risk in a first-diagnosed child or adolescent with T1DM. Preliminary data showed that children and adolescents with T1DM had higher concentrations of cystatin S, extracellular glycoprotein lacritin, beta-2-microglobulin and mesothelin, and lower concentrations of galectin-3, alpha-1-antitrypsin, neutrophil gelatinase-associated lipocalin and leukocyte elastase inhibitor, compared with the control group.
Conclusions: These preliminary data showed differential expression of tear proteins in children and adolescents with T1DM. Further bioinformatics analysis will identify tear biomarkers that might be used in assessing the risk of cognitive dysfunction early in diagnosis of T1DM.
15 Sep 2022 - 17 Sep 2022