A predictive model for lack of partial clinical remission in new-onset pediatric type 1 diabetes

Abstract

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.AimTo determine whether routinely obtainable clinical parameters predict non-remission in children and adolescents with new-onset T1D.Subjects and methodsData 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.ResultsNon-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.ConclusionsMore 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.

Remission phase in children diagnosed with type 1 diabetes in years 2012 to 2013 in Silesia, Poland: An observational study

“…First, children that achieved the PR period had higher weight and BMI SDS, as in another cohort studied in Poland . Our findings stay in controversy to results from other researches . Nevertheless, our result may be a significant observation that would stand in accordance with the acceleration hypothesis (Terry Wilkin 2001) .…”

Bringing Stem Cell‐Based Therapies for Type 1 Diabetes to the Clinic: Early Insights from Bioprocess Economics and Cost‐Effectiveness Analysis

“…The finding that the therapy would be cost saving for patients for whom ESRD is avoided is consistent with the current clinical development of devices allowing direct vascularization for the treatment of patients with a high risk of ESRD . The development of predictive models of diabetes‐related complications would help optimize the allocation of resources of these high‐value, high‐cost therapies under budget limitations. The cell‐loaded device price is one of the critical factors influencing the probability of cost‐effectiveness, and increased likelihood of reimbursement by healthcare payers in budget‐constrained scenarios.…”

Sex as a determinant of type 1 diabetes at diagnosis

“…The longer duration of symptoms before diagnosis has been shown to be associated with short or no clinical remission, a period characterized by a conspicuous fall in the exogenous insulin requirement and near normalization of glycemic control . According to earlier reports, boys have experienced partial clinical remission more often than girls, and the duration of the remission has been longer in male patients . This has been presumed to be due to a less aggressive disease process in males .…”