Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study

Abstract

OBJECTIVE To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia. RESEARCH DESIGN AND METHODS One hundred forty-four children with type 1 diabetes and 72 age-matched control subjects without diabetes (mean ± SD age at baseline 7.0 ± 1.7 years, 46% female) had unsedated MRI and cognitive testing up to four times over 6.4 ± 0.4 (range 5.3–7.8) years; HbA1c and continuous glucose monitoring were done quarterly. FreeSurfer-derived brain volumes and cognitive metrics assessed longitudinally were compared between groups using mixed-effects models at 6, 8, 10, and 12 years. Correlations with glycemia were performed. RESULTS Total brain, gray, and white matter volumes and full-scale and verbal intelligence quotients (IQs) were lower in the diabetes group at 6, 8, 10, and 12 years, with estimated group differences in full-scale IQ of −4.15, −3.81, −3.46, and −3.11, respectively (P < 0.05), and total brain volume differences of −15,410, −21,159, −25,548, and −28,577 mm3 at 6, 8, 10, and 12 years, respectively (P < 0.05). Differences at baseline persisted or increased over time, and brain volumes and cognitive scores negatively correlated with a life-long HbA1c index and higher sensor glucose in diabetes. CONCLUSIONS Detectable changes in brain volumes and cognitive scores persist over time in children with early-onset type 1 diabetes followed longitudinally; these differences are associated with metrics of hyperglycemia. Whether these changes can be reversed with scrupulous diabetes control requires further study. These longitudinal data support the hypothesis that the brain is a target of diabetes complications in young children.

The effect of do‐it‐yourself real‐time continuous glucose monitoring on psychological and glycemic variables in children with type 1 diabetes: A randomized crossover trial

“…Overall, time in hypoglycemia was similar with both interventions, and while DIY RT‐CGM did show small reductions in TBR, these were not statistically significant, this is possibly reflected in the FOH negative outcome. This improvement in TIR and time spent in hyperglycemia may be of particular importance in this younger age group due to the potentially damaging impacts of hyperglycemia on neuro‐developmental aspects 3,4 . These data are critical as families worldwide have adopted this cheaper RT‐CGM technology with no evidence of effectiveness to date 18 …”

“…Management of T1D is multifaceted and aims at controlling the risk of both acute and chronic complications as well as alleviating the impact of the disease and its management on the quality of life of affected children and their caregivers 2 . In addition, inadequate control of glucose levels and glucose variability, can have detrimental effect on brain development in children; thus improving time in range may help improve outcomes in this age group 3–5 . Current evidence‐based guidelines recommend intensive management with insulin of T1D to reduce and prevent diabetes‐related complications 2 .…”

Hybrid closed-loop insulin delivery versus sensor-augmented pump therapy in children aged 6–12 years: a randomised, controlled, cross-over, non-inferiority trial

“…1 Intensive diabetes treatment benefits all patients with type 1 diabetes but is even more crucial before 10 years of age, 2 when poor glycaemic control markedly increases the cardiovascular risk 2 and can adversely affect brain and cognitiveskills development. 3,4,5,6 The 2018 American Diabetes Association and International Society for Paediatric and Adolescent Diabetes (ISPAD) guidelines now recommend that glycated haemoglobin A 1c (HbA 1C ) be kept at less than 7% (<53 mmol/mol), 7 which corresponds to a time in range (TIR) greater than 65-75% as measured by CGM. 8,9 For patients with hypoglycaemia unawareness or limited access to insulin analogues or advanced insulin delivery devices, the target is a TIR greater than 60%.…”

Continuous glucose monitoring use and glucose variability in very young children with type 1 diabetes (VibRate): A multinational prospective observational real‐world cohort study

“…1 There is increasing evidence that both glycaemic excursions early in the disease course and high glucose concentrations have detrimental effects on the developing brain of young children, suggesting it is critical to mitigate exposure to hyperglycaemia and pronounced glucose fluctuations. [2][3][4] Whereas HbA1c goals must be personalized and tailored over time, reaching the HbA1c target of HbA1c below 7% (<53 mmol/mol) remains elusive for most children with T1D. Even fewer attain HbA1c below 6.5% (<48 mmol/mol), a newer consideration, because more stringent goals are associated with better glycaemic outcomes without an increased frequency of acute complications.…”