OBJECTIVES, MATERIALS AND METHODS
This retrospective study described the partial remission phase (as defined by the IDAA1C definition) in a group of 239 children followed in UCL’s department of pediatric endocrinology. The factors potentially associated with the occurrence of remission (age at diagnosis, gender, biological parameters) were evaluated, as was the influence of partial remission on the frequency of severe hypoglycemic episodes during the first 2 years of diabetes. In the second part of this work, an alternative formula defining partial remission was elaborated. This new definition aims at replacing the “insulin doses” parameter of the IDAA1C definition by measurable parameters easily accessible during routine clinical follow-up. For this purpose, the capacity of different parameters reflecting glycemic variability to predict IDAA1C values was assessed using multiple linear regression.
RESULTS
In the 239 patients included in this study, partial remission, as defined by the IDAA1C, occurred in 71.1% of children, with a mean duration of 8.9 months (range: 1.8–44.3 months, median: 4.7 months). The highest prevalence of remission was observed 3 months after diagnosis (62.4%). Children aged 5 to 10 years at diagnosis were significantly more likely to present remission as compared to younger children (<5 years). At diagnosis, the factors significantly associated with higher remission rates were the absence of ketoacidosis and high C-peptide levels. No association was found between gender, the presence of anti-islet cell and anti-transglutaminase antibodies, the month of the year and season when the diagnosis was made, and the occurrence of a remission. Children who experienced remission in the first months of diabetes had significantly reduced HbA1C values at 1 and 2 years following diagnosis and significantly increased C-peptide values. A lower frequency of severe hypoglycemic episodes was observed among the children in the remission group, but only in boys and children younger than 10 years at diagnosis. In the second part of this study, the following formula was elaborated: GVAA1C (Glycemic Variability-Adjusted A1C) = HbA1C – 3 x p-normoglycemic values [2]. It predicts IDAA1C values with a R2 of 0.71. With a threshold of 4.5, this alternative formula identifies the presence of remission, as defined by the IDAA1C, with a sensitivity and specificity of 72.3% and 92%, respectively.
DISCUSSION AND CONCLUSION
Many authors have already attempted to characterize the remission phase, allowing to outline some factors significantly associated with the occurrence of partial remission. In line with previous findings, this study points out the negative influence of ketoacidosis, younger age, and lower residual insulin secretion at diagnosis, these three factors being associated with reduced remission rates. However, the consequences of remission on the disease course remains unclear. Some of our results suggest that the occurrence of a remission at the onset of diabetes might be associated with lower rates of complications, even after the end of this period. However, studies with a longer follow-up are required to confirm and specify this hypothesis. In order to propose a more objective and reproducible definition of remission by reducing the confounding factors influencing the IDAA1C, this study elaborated the GVAA1C as a valid alternative definition of partial remission in type 1 diabetes. This new formula identifies the presence of a remission in clinical routine and approaches the IDAA1C values relying exclusively on routinely measured clinical parameters.
[1] P. Mortenson et al., “New Definition for the Partial Remission Period in Children and Adolescents with Type 1 Diabetes,” Diabetes Care. 2009.
[2] N. Nielens et al., “Integration of Routine Parameters of Glycemic Variability in a Simple Screening Method for Partial Remission in Children with Type 1 Diabetes,” J Diabetes Res. 2018.