Integration of Routine Parameters of Glycemic Variability in a Simple Screening Method for Partial Remission in Children with Type 1 Diabetes

Abstract

Although different criteria were used to define partial remission in type 1 diabetes, the IDAA1C formula has prevailed as it correlates with stimulated C-peptide levels. Our retrospective study evaluated clinical variables associated with the occurrence of IDAA1C-defined partial remission in a series of 239 pediatric patients. Diabetic ketoacidosis and age at diagnosis, but no other clinical feature, influenced the occurrence of remission. We then evaluated whether parameters of glycemic variability used in clinical routine may reliably define partial remission, as these would alleviate confounding factors related to insulin treatment. Using multiple linear regression, we observed that HbA1C levels and percentage of normoglycemia were efficient and sufficient to predict partial remission. These parameters were entered into a formula, called glycemic target-adjusted HbA1C (GTAA1C), that corresponded to HbA1C(%) − (3 × % of normoglycemic values(70–180 mg/dL)). With a threshold of 4.5, this alternative formula predicted partial remission with a sensitivity and a specificity of 72.3% and 92%, respectively, and yielded strong correlation with IDAA1C levels and BETA-2 score, which is a correlate of β-cell function after islet transplantation. We propose GTAA1C, based on routine and objective markers of glycemic variability, as a valid alternative for definition of partial remission in type 1 diabetes.

Features of partial remission in children with type 1 diabetes using the insulin dose-adjusted A1c definition and risk factors associated with nonremission

“…In this study, the frequency of PR in our cohort was 45.6%. This number is comparable to that reported by other published studies that also defined PR using the IDAA1c criteria (range, 35%–71.1%) [ 16 - 21 ]. IDAA1c is an easy-to-use formula in a clinic setting that gives reasonable sensitivity and specificity in identifying PR status and guiding management planning.…”

“…However, in general, more studies have suggested that an older age of onset is associated with a greater chance of PR, especially when compared to the group of those younger than 5 years of age. 1,4,17,20,21,27,33) In particular, prepubertal children older than 5 years of age appeared to have the greatest likelihood of PR. There were several postulations of why very young children often do not enter into PR.…”

“…This number is comparable to that reported by other published studies that also defined PR using the IDAA1c criteria (range, 35%-71.1%). [16][17][18][19][20][21] IDAA1c is an easy-to-use formula in a clinic setting that gives reasonable sensitivity and www.e-apem.org specificity in identifying PR status and guiding management planning. However, it has not yet been validated in patients using insulin pumps who often require lower TDDs relative to patients receiving multiple daily injections.…”

“…Using the TDD of less than 0.3 unit/kg/day definition might demonstrate a lower sensitivity in the Asian population and therefore would not be applicable in our locality. Meanwhile, a more recent study published in 2018 proposed another definition for PR, referred to as the glycemic target-adjusted HbA1c [ 21 ], but more research is required for its validation, including its applicability in populations similar to our study cohort.…”

Capturing residual beta cell function in type 1 diabetes

“…This algorithm was validated in subsequent studies, and the IDAA 1c has prevailed as a measurement for partial remission [29][30][31][32][33]. It has also been proposed that a total daily dose of insulin of ≤0.3 U kg −1 day −1 performed equally well as IDAA 1c in predicting remission [34], though not thoroughly tested.…”