ESPE Abstracts

Aims: In children with new-onset type 1 diabetes mellitus (T1D), insulin dose regimens vary substantially. According to current ISPAD recommendations, the initial total daily dose (TDD) should range from 0.7 to 1.0 IU/kg BW/day. Adjusting TDD to achieve normal blood glucose concentration can take several days. The primary objectives of our INSENODIAB (INsulin SEnsitivity in New Onset type 1 DIABetes) study were to assess how patient characteristics influence insulin dose requirements in children and adolescents with new-onset T1D and to establish a predictive model of their recommended TDD. The second objective was to evaluate potential correlations between insulin dose requirements and patient outcomes at 3 and 12 months after diagnosis.

Methods: INSENODIAB study is composed of two distinct cohorts: rINSENODIAB (retrospective) and pINSENODIAB (prospective). Chart review was conducted for children (6 months-18 years) admitted for new-onset T1D between 2013 and 2020. Descriptive statistics were computed for demographics, clinical and paraclinical data. Multivariable linear regression was performed using all baseline variables from admission, with a 5% nominal Type I error. Goodness of fit was characterized by the adjusted R-square and the Pearson correlation between the observed and predicted TDD. The model was then applied on pINSENODIAB for robustness assessment.

Results: Complete clinical records were available for 103 patients in rINSENODIAB and 80 patients in pINSENODIAB with a median age of 9.2 years old (IQR 6.9) and 10.6 years old (IQR 5.6) respectively. Median TDD was 1.1 IU/kg BW/day (IQR 0.5). Using a multivariable analysis, we computed a predictive model of optimal TDD as such: (TDD (IU/d) = [0,09 x Age2] + [0,68 x %Weight Loss] + [28,60 x Veinous pH] – [1,03 x Veinous bicarbonates] + [0,81 x Weight] – 194,63). This model was then independently validated in the multicentric pINSENODIAB cohort (r= 0.74, P<0.05). In our cohort, no correlation existed between TDD and glucose homeostasis markers (IDAA1C, C-peptide) at 3 and 12 months after diabetes onset. These results suggest that TDD at diagnosis mainly reflects an acute metabolic state rather than a particular patient phenotype.

Conclusions: In newly diagnosed children with T1D, the square of age, percentage of weight loss, weight, veinous pH and bicarbonates influenced the optimal insulin TDD. These results helped us develop a dosing algorithm to potentially reduce the time currently needed to stabilize glycemic control in children and adolescents with new-onset T1D as well as help to transition diabetes care to more individual treatment regimens.