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

Abstract

We sought to evaluate features of partial remission (PR) in children with type 1 diabetes mellitus (T1DM) using the insulin-dose adjusted A1c (IDAA1c) definition and to identify risk factors associated with nonremission. Methods: Medical records of patients with newly diagnosed T1DM between January 1, 2008, and June 30, 2018, were retrospectively reviewed. Hemoglobin A1c (HbA1c) readings and insulin total daily doses (TDDs) of each patient at each follow-up visit were obtained with IDAA1c values calculated. PR was defined as an IDAA1c score of 9 points or less within 6 months of diagnosis. The trends of HbA1c and TDD within 2 years after diagnosis were compared between remitters and nonremitters. Factors that may predict the occurrence of PR were studied, with their relative risks of nonremission calculated. Results: PR occurred in 26 patients (45.6%), including 8 girls and 18 boys, with a median duration of 8 months. The frequency of remission in male patients was significantly higher (P=0.002) and the relative risk of female sex with nonremission was 2.20 (95% confidence interval [CI], 1.24-3.91), which remained significant when adjusted by multivariate regression modeling. The initial HbA1c level at diagnosis was also significantly higher in the nonremission group (P=0.029), with a relative risk of 1.12 (95% CI, 1.01-1.25). Both HbA1c (P=0.012) and TDD (P=0.006) were significantly lower within 2 years after diagnosis among remitters than in nonremitters. TDD was significantly lower in male patients (P=0.029) during the same period, while there was no significant difference in HbA1c level between male and female patients (P=0.163). Conclusion: Both the initial HbA1c level at diagnosis and sex were factors associated with the occurrence of PR. Female sex was an independent risk factor of nonremission, likely resulting from a higher insulin requirement in female T1DM patients.

Complete remission in children and adolescents with type 1 diabetes mellitus—prevalence and factors

“…Another factor of remission identified by our study was the severity of diabetes at the onset, as the remitters had significantly lower HbA1c levels at the time of diagnosis. Higher HbA1c levels reflect longer duration and higher values of hyperglycaemia prior to the diagnosis of diabetes and was also described by Wong et al as a negative factor for remission 22 . In our univariate analyses we also found other factors of remission onset linked to the lower severity of diabetes previously described by others, i.e.…”

Candidate Biomarkers for the Prediction and Monitoring of Partial Remission in Pediatric Type 1 Diabetes

“…In general, children experience remission to a higher extend than adults, and within the first group, the probability of remaining in remission is greater as the onset age increased (70). Different regression analyses showed that higher pH and bicarbonate levels, higher BMI, male sex, and lower HbA1c, insulin dose, and numbers of islet antibodies at T1D onset are predictors of remission (13,14,(70)(71)(72). However, the prediction of remission using immunological data is rather scarce.…”

“…Unfortunately, the mechanisms underlying the PR phase are poorly characterized, but this natural phenomenon has been attributed to both the reduction of glucose toxicity after the initiation of the insulin therapy and the consequent β-cell rest, recovery, and regeneration with improved endogenous insulin production ( 12 ). At a clinical level, bicarbonate concentrations >15 mg/dl, age >5 years, male sex, higher body mass index (BMI) values, lower HbA1c levels, and <3 diabetes-associated autoantibodies can predispose to PR in children and adolescents with new-onset T1D ( 13 , 14 ). Furthermore, mechanisms of immune regulation are non-linear along the natural history of T1D—matching well with the proposed relapsing-remitting character of the disease course—and the PR phase is associated with these immunomodulatory changes ( 15 , 16 ).…”

Early weight gain after diagnosis may have an impact on remission status in children with new‐onset type 1 diabetes mellitus

“…Previous studies investigating the epidemiology of remission in children with T1DM demonstrated that various parameters could affect the development of PR. 2,[23][24][25][26] In some publications, it has been reported that female patients with T1DM need more exogenous insulin than males during both the prepubertal and pubertal periods. 27,28 Furthermore, it is known that the insulin sensitivity of patients with T1DM differs in a wide range and is lower in female patients.…”

“…However, after adjustment, the only independent factor facilitating the development of PR was male sex. Previous studies investigating the epidemiology of remission in children with T1DM demonstrated that various parameters could affect the development of PR 2,23–26 . In some publications, it has been reported that female patients with T1DM need more exogenous insulin than males during both the prepubertal and pubertal periods 27,28 .…”