What can we learn from β-cell failure biomarker application in diabetes in childhood? A systematic review

Abstract

Background: The prevalence of diabetes as a catastrophic disease in childhood is growing in the world. The search for novel biomarkers of β-cell failure has been an elusive task because it requires several clinical and biochemical measurements in order to integrate the risk of metabolic syndrome.

Aim: To determine which biomarkers are currently used to identify β-cell failure among children and adolescents with high risk factors for diabetes mellitus.

Methods: This systematic review was carried out using a modified version of the PICO protocol (Participants/Intervention/Comparison/Outcome). Once our research question was established, terms were individually researched on three different databases (PubMed, BIREME and Web of Science). The total articles obtained underwent a selection process from which the 78 most relevant articles were retrieved to undergo further analysis. They were assessed individually according to quality criteria.

Results: First, we made the classification of the β-cell-failure biomarkers by the target tissue and the evolution of the disease, separating the biomarkers in relation to the types of diabetes. Second, we demonstrated that most biomarkers currently used as early signs of β-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes. Third, we explored the novelties of diabetes as a protein conformational disease and the novel biomarker called real human islet amyloid polypeptide amyloid oligomers. Finally, we ended with a discussion about the best practice of validation and individual control of using different types of biomarkers in type 1 and type 2 diabetes in order to assess the role they play in the progress of diabetes in childhood.

Conclusion: This review makes widely evident that most biomarkers currently used as early signs of β-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes. Landing in the clinical practice we propose that real human islet amyloid polypeptide amyloid oligomers is good for identifying patients with β-cell damage and potentially could substitute many biomarkers.

Keywords: Adolescents; Biomarker; Children; Diabetes mellitus; Metabolic syndrome; β-cell failure.

Figure 1

Modified PICO (PIO) approach for the systematic review. P (Participants) I (Intervention) and O (Outcome). Flowchart review process for the analyzed articles.

Figure 2

Global view of the main biomarkers analyzed on the articles included for this review. The biomarkers are divided into the ones that substantially appear on early beta cell damage (characterized by increased insulin and lipid and islet amyloid polypeptide secretion) and increased insulin resistance and of late beta cell damage (characterized by increased oxidative stress and insulin resistance, a markedly insulin secretion and an impaired mitochondrial function, which translates into islet amyloid polypeptide fibrillation). RIAO: Real human islet amyloid polypeptide amyloid oligomers; FMD: Flow-mediated dilatation; CAM: Cytoadhesive molecule; hs-CRP: High-sensitivity C-reactive protein.

Figure 3

Diagnostic methods found in the articles included for this review. The methods are ordered from the most used to the least used. The enzyme-linked immunosorbent assay was the most commonly used method; a total of 8 articles used it as a diagnostic method. ELISA: Enzyme-linked immunosorbent assay; qt-PCR: Quantitative polymerase chain reaction.