Cognitive disorders in type 1 diabetes: Role of brain glucose variation, insulin activity and glucocorticoid exposure

Background: The number of patients with type 2 diabetes (T2D) and type 1 diabetes (T1D) is on the rise, partly due to a global increase in new T1D cases among children. Beyond the well-documented microvascular and macrovascular complications, there is now substantial evidence indicating that diabetes also impacts the brain, leading to neuropsychological impairments. The risk of developing neuropsychiatric symptoms is notably higher in childhood due to the ongoing maturation of the brain, which makes it more susceptible to damage. Despite this awareness, the specific effects of diabetes on cognitive function remain poorly understood. Summary: This review synthesizes literature on the impact of diabetes on cognition and its relationship with brain structural changes. It presents data and hypotheses to explain how T1D contributes to cognitive dysfunction, with a particular focus on children and adolescents. The emphasis on the pediatric population is intentional, as young diabetic patients typically have fewer comorbidities, reducing confounding factors and simplifying the investigation of cognitive alterations. Key Message: We examine the roles of hypo- and hyperglycemia, as well as the emerging role of glucocorticoids in the development of neuropsychological disorders. When specific mechanisms related to T1D are available, they are highlighted; otherwise, data and hypotheses applicable to both T1D and T2D are discussed.