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A predictive model for lack of partial clinical remission in new-onset pediatric type 1 diabetes
Katherine R Marino1, Rachel L Lundberg1, Aastha Jasrotia1
1Division of Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Insights
Over half of new type 1 diabetes (T1D) patients don't achieve partial clinical remission (PCR), increasing long-term complication risks. Early identification of non-remitters using clinical factors can guide targeted therapies for better glycemic control.
Area of Science:
- Pediatric Endocrinology
- Diabetes Mellitus Research
- Autoimmune Disease Studies
Background:
- More than 50% of children and adolescents with new-onset type 1 diabetes (T1D) fail to achieve partial clinical remission (PCR).
- Lack of PCR in T1D is linked to increased risk of long-term diabetes mellitus complications.
- Early identification of non-remitters is crucial for improving initial glycemic control.
Purpose of the Study:
- To identify routinely obtainable clinical parameters that predict non-remission in pediatric patients with new-onset T1D.
- To develop a predictive model for non-remission in children and adolescents with T1D.
Main Methods:
- A cohort of 204 children and adolescents (ages 2-14) with new-onset T1D were monitored for 36 months.
- Partial clinical remission (PCR) was defined as an insulin-dose adjusted hemoglobin A1c of ≤9.
- Clinical parameters including autoantibody levels and bicarbonate levels at diagnosis were analyzed.
Main Results:
- 57.8% of subjects did not achieve non-remission.
- Predictors of non-remission included 4+ diabetes-associated autoantibodies (OR=9.90), age <5 years (OR=5.38), and bicarbonate <15 mg/dL at diagnosis (OR=3.71).
- A predictive model using bicarbonate <15 mg/dL, age <5 years, female sex, and >3 autoantibodies demonstrated an AUC of 0.73 for predicting non-remission.
Conclusions:
- A significant proportion of children and adolescents with new-onset T1D do not achieve partial clinical remission.
- A predictive model incorporating bicarbonate levels, age, sex, and autoantibody count can identify non-remitters with 73% accuracy.
- Early identification of non-remitters allows for targeted therapies to mitigate dysglycemia and reduce long-term complications.
Importance:
>50% of patients with new-onset type 1 diabetes (T1D) do not enter partial clinical remission (PCR); early identification of these patients may improve initial glycemic control and reduce long-term complications.
Aim:
To determine whether routinely obtainable clinical parameters predict non-remission in children and adolescents with new-onset T1D.
Subjects And Methods:
Data on remission were collected for the first 36 months of disease in 204 subjects of ages 2-14 years with new-onset type 1 diabetes. There were 86 remitters (age 9.1±3.0y; male 57%), and 118 non-remitters (age 7.0±3.1y; male 40.7%). PCR was defined as insulin-dose adjusted hemoglobin A1c of ≤9.
Results:
Non-remission occurred in 57.8% of subjects. Univariable analysis showed that the risk for non-remission was increased 9-fold in patients with 4 diabetes-associated auto-antibodies (OR = 9.90, p = 0.010); 5-fold in patients <5 years old (odds ratio = 5.38, p = 0.032), 3-fold in those with bicarbonate of <15 mg/dL at diagnosis (OR = 3.71, p = 0.008). Combined estimates of risk potential for HC03 and the number of autoantibodies by multivariable analysis, adjusted for BMI standard deviation score, showed HC03 <15 mg/dL with a clinically significant 10-fold risk (OR = 10.1, p = 0.074); and the number of autoantibodies with a 2-fold risk for non-remission (OR = 1.9, p = 0.105). Male sex and older age were associated with decreased risk for non-remission. A receiver-operating characteristic curve model depicting sensitivity by 1-specificity for non-remission as predicted by bicarbonate <15 mg/dL, age <5y, female sex, and >3 diabetes-associated autoantibodies had an area under the curve of 0.73.
Conclusions:
More than 50% of children and adolescents with new-onset T1D do not undergo partial clinical remission and are thus at an increased risk for long-term complications of diabetes mellitus. A predictive model comprising of bicarbonate <15 mg/dL, age <5y, female sex, and >3 diabetes-associated autoantibodies has 73% power for correctly predicting non-remission in children and adolescents with new-onset T1D. Early identification of these non-remitters may guide the institution of targeted therapy to limit dysglycemia and reduce the prevalence of long-term deleterious complications.
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