HbA1c Variability as a Predictor of Neurocognitive Decline in Children With Type 1 Diabetes

Children with type 1 diabetes mellitus (T1DM) are vulnerable to neurocognitive impairments due to fluctuating glycemic control. Recent evidence suggests that long-term variability in HbA1c, rather than mean HbA1c alone, may be a more sensitive indicator of metabolic instability contributing to cognitive decline.

This study aimed to evaluate the association between HbA1c variability and neurocognitive performance in children with T1DM and to determine whether HbA1c variability serves as an independent predictor of neurocognitive decline.

A retrospective analysis was conducted at Khyber Teaching Hospital, Peshawar, Pakistan, including 180 children with T1DM (96 males, 53.3%; 84 females, 46.7%) aged 12.6 ± 3.4 years. Data from the preceding 24 months were reviewed, including serial HbA1c values, clinical characteristics, and standardized neurocognitive test scores. HbA1c variability was quantified using standard deviation (SD) and coefficient of variation (CV). Participants were categorized into high-variability (CV > 8%) and low-variability (CV ≤ 8%) groups. Cognitive domains assessed included full-scale intelligence quotient (IQ), working memory, processing speed, attention, and executive function. Statistical analyses included correlation and multiple linear regression to identify independent predictors of cognitive outcomes.

The mean duration of diabetes was 5.8 ± 2.1 years, and the mean HbA1c was 8.6 ± 1.2%. Children in the high-variability group (n = 89, 49.4%) showed significantly lower full-scale IQ (89.0 ± 10.1 vs. 95.8 ± 9.4, p < 0.001), working memory (85.9 ± 9.1 vs. 93.6 ± 10.3, p = 0.001), processing speed (86.7 ± 10.7 vs. 94.1 ± 11.5, p = 0.003), and executive function (86.5 ± 8.8 vs. 92.9 ± 9.5, p = 0.012) compared with the low-variability group. HbA1c CV showed the strongest negative correlation with full-scale IQ (r = -0.562, p < 0.05). In multivariate regression, HbA1c CV (β = -0.42, p < 0.001) and hypoglycemia frequency (β = -0.21, p = 0.008) independently predicted lower IQ scores.

Higher HbA1c variability is significantly associated with poorer neurocognitive outcomes in children with T1DM, independent of mean HbA1c levels. Long-term glycemic stability may therefore be a crucial target to preserve cognitive function in pediatric diabetes care.