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Poor glycaemic control is associated with increased risk of neurodevelopmental disorders in childhood-onset type 1
Shengxin Liu1, Ralf Kuja-Halkola2, Henrik Larsson2,3
1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden. Shengxin.liu@ki.se.
Insights
Childhood-onset type 1 diabetes increases neurodevelopmental disorder risk, especially with poor glycemic control (high HbA1c). Regular follow-ups are recommended for these patients.
Area of Science:
- Endocrinology
- Neuroscience
- Pediatrics
Background:
- Type 1 diabetes (T1D) is a chronic condition affecting children.
- Glycemic control is crucial in managing T1D and preventing complications.
- Neurodevelopmental disorders (NDDs) can have long-term impacts on individuals.
Purpose of the Study:
- To examine the association between childhood-onset T1D and the risk of subsequent NDDs.
- To investigate the role of glycemic control (HbA1c levels) in this association.
- To compare risks between T1D patients and the general population, and among T1D patients with varying glycemic control.
Main Methods:
- A Swedish population-based cohort study using health registers (1973-2013).
- Identified 8430 patients with childhood-onset T1D and 84,300 matched controls.
- Used Cox models to assess the effect of HbA1c on NDD risk (ADHD, ASD, intellectual disability).
Main Results:
- Individuals with childhood-onset T1D had a 1.31-fold increased risk of NDDs compared to the general population.
- Higher HbA1c levels correlated with increased NDD risk.
- Patients with mean HbA1c >8.6% showed significantly higher risks for NDDs, ADHD, ASD, and intellectual disability compared to those with HbA1c <7.5%.
Conclusions:
- Childhood-onset T1D is linked to a higher risk of NDDs.
- Poor glycemic control (high HbA1c) substantially elevates this risk.
- Consider routine neurodevelopmental follow-up for T1D patients, particularly those with suboptimal glycemic control.
Aims/Hypothesis:
The aim of this study was to investigate the effect of childhood-onset type 1 diabetes on the risk of subsequent neurodevelopmental disorders, and the role of glycaemic control in this association. We hypothesised that individuals with poor glycaemic control may be at a higher risk of neurodevelopmental disorders compared with the general population, as well as compared with individuals with type 1 diabetes with adequate glycaemic control.
Methods:
This Swedish population-based cohort study was conducted using data from health registers from 1973 to 2013. We identified 8430 patients with childhood-onset type 1 diabetes (diagnosed before age 18 years) with a median age of diabetes onset of 9.6 (IQR 5.9-12.9) and 84,300 reference individuals from the general population, matched for sex, birth year and birth county. Cox models were used to estimate the effect of HbA1c on the risk of subsequent neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability.
Results:
During a median follow-up period of 5.6 years, 398 (4.7%) individuals with type 1 diabetes received a diagnosis of any neurodevelopmental disorder compared with 3066 (3.6%) in the general population, corresponding to an adjusted HR (HRadjusted) of 1.31 (95% CI 1.18, 1.46) after additionally adjusting for other psychiatric morbidity prior to inclusion, parental psychiatric morbidity and parental highest education level. The risk of any neurodevelopmental disorder increased with HbA1c levels and the highest risk was observed in patients with mean HbA1c >8.6% (>70 mmol/mol) (HRadjusted 1.90 [95% CI 1.51, 2.37]) compared with reference individuals without type 1 diabetes. In addition, when compared with patients with diabetes with HbA1c <7.5% (<58 mmol/mol), patients with HbA1c >8.6% (>70 mmol/mol) had the highest risk of any neurodevelopmental disorder (HRadjusted 3.71 [95% CI 2.75, 5.02]) and of specific neurodevelopmental disorders including ADHD (HRadjusted 4.16 [95% CI 2.92, 5.94]), ASD (HRadjusted 2.84 [95% CI 1.52, 5.28]) and intellectual disability (HRadjusted 3.93 [95% CI 1.38, 11.22]).
Conclusions/Interpretation:
Childhood-onset type 1 diabetes is associated with an increased risk of neurodevelopmental disorders, with the highest risk seen in individuals with poor glycaemic control. Routine neurodevelopmental follow-up visits should be considered in type 1 diabetes, especially in patients with poor glycaemic control.
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