Characteristics and determinants of partial remission in children with type 1 diabetes using the insulin-dose-adjusted A1C definition

Abstract

To evaluate the characteristics and determinants of partial remission (PR) in Belgian children with type 1 diabetes (T1D), we analyzed records of 242 children from our center. Clinical and biological features were collected at diagnosis and during follow-up. PR was defined using the insulin-dose-adjusted A1C definition. PR occurred in 56.2% of patients and lasted 9.2 months (0.5 to 56.6). 25.6% of patients entered T1D with DKA, which correlated with lower PR incidence (17.6% versus 82.3% when no DKA). In our population, lower A1C levels at diagnosis were associated with higher PR incidence and in young children (0-4 years) initial A1C levels negatively correlated with longer PR. Early A1C levels were predictive of PR duration since 34% of patients had long PRs (>1 year) when A1C levels were ≤ 6% after 3 months whereas incidence of long PR decreased with higher A1Cs. C-peptide levels were higher in patients entering PR and remained higher until 3 years after diagnosis. Initial antibody titers did not influence PR except for anti-IA2 titers that correlated with A1C levels after 2 years. Presence of 2 versus 1 anti-islet antibodies correlated with shorter PR. PR duration did not influence occurrence of severe hypoglycemia or diabetes-related complications but was associated with lower A1C levels after 18 months. We show that, at diagnosis of T1D, parameters associated with β-cell mass reserve (A1C, C-peptide, and DKA) correlate with the occurrence of PR, which affects post-PR A1C levels. Further research is needed to determine the long-term significance of PR.

Figure 1

Characteristics of PR, A1C at diagnosis and during follow-up. (a) Box plots with ranges showing no difference in PR duration between gender and age subgroups. [+] shows means for each group. (b) Distribution of PR durations among remitters (n = 136). (c) Evolution of A1C levels during follow-up. (d) A1C levels at diagnosis among gender and age subgroups. (e) Graphs showing correlation between PR duration and A1C levels 2, 3, and 5 years after follow-up (resp., A1C+2y, A1C+3y, and A1C+5y). PR durations were grouped to correspond to 3 months ± 15 days and 6, 9, 12, and 18 months ± 30 days. All bars were shown with SEM. *P < 0.05, ***P < 0.001, and ****P < 0.0001 compared with indicated groups.

Figure 2

Influence of early A1C levels on PR duration and characteristics of C-peptide levels among PR, age, and gender subgroups. (a) Graph showing negative correlation between A1C levels (subgroups indicated) at 3-, 6-, 9-, and 12-month follow-up and PR duration. (b) C-peptide levels were higher in patients entering PR when evaluated at diagnosis and after 1, 2, and 3 years. (c) Differences in C-peptide levels among PR, gender, and age subgroups. All bars were shown with SEM. *P < 0.05, **P < 0.01, and ****P < 0.0001 compared with indicated groups.