Approaches to Measuring Beta Cell Reserve and Defining Partial Clinical Remission in Paediatric Type 1 Diabetes

Context: Type 1 diabetes (T1D) results from the autoimmune T-cell mediated destruction of pancreatic beta cells leading to insufficient insulin secretion. At the time of diagnosis of T1D, there is residual beta cell function that declines over the subsequent months to years. Recent interventions have been approved to preserve beta cell function in evolving T1D. Objective: The aim of this review is to summarise the approaches used to assess residual beta cell function in evolving T1D, and to highlight potential future directions. Methods: Studies including subjects aged 0 to 18 years were included in this review. The following search terms were used; "(type 1 diabetes) and (partial remission)" and "(type 1 diabetes) and (honeymoon)". References of included studies were reviewed to determine if additional relevant studies were eligible. Results: There are numerous approaches to quantifying beta cell reserve in evolving T1D. These include c-peptide measurement after a mixed meal or glucagon stimuli, fasting c-peptide, the urinary c-peptide/creatinine ratio, insulin dose-adjusted haemoglobin A1c, and other clinical models to estimate beta cell function. Other biomarkers may have a role, including the proinsulin/c-peptide ratio, cytokines, and microRNA. Studies using thresholds to determine if residual beta cell function is present often differ in values used to define remission. Conclusions: As interventions are approved to preserve beta cell function, it will become increasingly necessary to quantify residual beta cell function in research and clinical contexts. In this report, we have highlighted the strengths and limitations of the current approaches.