Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

Abstract

Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the β-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of β-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children. Shortly after diagnosis, T1D patients often experience partial remission called “honeymoon phase,” which lasts a few months, with minor requirements of exogenous insulin. In this stage, the remaining β-cells are still able to produce enough insulin to reduce the administration of exogenous insulin. A recovery of immunological tolerance to β-cell autoantigens could explain the regeneration attempt in this remission phase. This mini-review focuses on the remission phase in childhood T1D. Understanding this period and finding those peripheral biomarkers that are signs of immunoregulation or islet regeneration could contribute to the identification of patients with a better glycaemic prognosis and a lower risk of secondary complications. This remission phase could be a good checkpoint for the administration of future immunotherapies.

Remission phase in children diagnosed with type 1 diabetes in years 2012 to 2013 in Silesia, Poland: An observational study

“…Second, we revealed that although there was no difference in DKA prevalence between patients with and without PR, remitters had significantly higher first measured blood pH at T1D onset, and it was the most important predictor of PR occurrence. These results partially confirm the observations of other authors that children with DKA at first hospital admission are less probable to enter PR . It may be postulated that patients with higher pH were in a better clinical condition—probably because the amount or functional capacity of remaining beta cell was in these individuals higher at diagnosis.…”

“…Interestingly, also in a cohort of adolescents with T1D an autologous non‐myeloablative hematopoietic stem cell transplantation was more effective in patients without DKA at diagnosis . In this study, we proved additionally that with rising pH values the duration of PR increased; however, results from other cohorts are not unequivocal …”

“…It may be postulated that patients with higher pH were in a better clinical condition—probably because the amount or functional capacity of remaining beta cell was in these individuals higher at diagnosis. In addition, insulin treatment targeting at normoglycemia that is initiated directly at onset could have played a role in sustaining their function longer . Interestingly, also in a cohort of adolescents with T1D an autologous non‐myeloablative hematopoietic stem cell transplantation was more effective in patients without DKA at diagnosis .…”

“…Most of these young patients are using insulin pumps. It may be that such an intensive, aggressive approach results in higher remission rates, regardless of age . And this hypothesis may be partially supported by higher remission rates in Poland in general when compared with other countries—as it was discussed above.…”

“…Other studies investigating the pediatric T1D population documented a highly variable prevalence of PR—between 25% and 100% . This wide range may reflect country differences regarding the treatment model and target at T1D onset as well as the use of different definitions of PR …”