Clinical Aspects and Molecular Mechanisms of Cognitive Dysfunction in Children and Adolescents with Type 1 Diabetes

Type 1 diabetes (T1D) constitutes a chronic metabolic disorder attributed to the autoimmune destruction of insulin-producing pancreatic β cells, which most frequently occurs in childhood. Long-term complications of T1D are expected to occur mainly in adult life, whereas cognitive dysfunction can also occur in children and adolescents with T1D. Most studies demonstrate mild cognitive impairment, especially in the domains of memory, attention and executive functions, all of which affect academic performance, which may also negatively influence adherence to appropriate glucose monitoring and insulin treatment in children and adolescents with T1D. As a result, mild cognitive dysfunction can be an obstacle to both optimal glycemic control during childhood and adolescence and academic achievements for young individuals with T1D. The major metabolic changes occurring around the onset of diabetes, such as severe hyperglycemia and diabetic ketoacidosis, may have a negative impact on brain plasticity during this vulnerable period of neurodevelopment, especially in children diagnosed at a younger age. The pathophysiological mechanisms involved are closely related to increased oxidative stress and the accumulation of advanced glycation end products in the brain, thus leading to neuron cell damage and apoptosis. On the other hand, hypoglycemic episodes and glucose fluctuations may also impair neuronal integrity. The aim of the current narrative review is therefore to present the existing literature data on the clinical aspects, risk factors and molecular mechanisms associated with cognitive dysfunction in children and adolescents with T1D.