Relationships Between Hyperglycemia and Cognitive Performance Among Adults With Type 1 and Type 2 Diabetes

Abstract

OBJECTIVE -Hyperglycemia is a common event among patients with type 1 and type 2 diabetes. While the cognitive-motor slowing associated with hypoglycemia is well documented, the acute effects of hyperglycemia have not been studied extensively, despite patients' reports of negative effects. This study prospectively and objectively assessed the effects of hyperglycemia on cognitive-motor functioning in subjects' natural environment.RESEARCH DESIGN AND METHODS -Study 1 investigated 105 adults with type 1 diabetes (mean age 37 years and mean duration of diabetes 20 years), study 2 investigated 36 adults with type 2 diabetes (mean age 50 years and mean duration of diabetes 10 years), and study 3 investigated 91 adults with type 1 diabetes (mean age 39 years and mean duration of diabetes 20 years). Subjects used a hand-held computer for 70 trials over 4 weeks, which required them to complete various cognitive-motor tasks and then measure and enter their current blood glucose reading.RESULTS -Hyperglycemia (blood glucose Ͼ15 mmol/l) was associated with slowing of all cognitive performance tests (P Ͻ 0.02) and an increased number of mental subtraction errors for both type 1 and type 2 diabetic subjects. The effects of hyperglycemia were highly individualized, impacting ϳ50% of the subjects.CONCLUSIONS -Acute hyperglycemia is not a benign event for many individuals with diabetes, but it is associated with mild cognitive dysfunction. Diabetes Care 28:71-77, 2005P atients with diabetes often report acute and transient cognitive disruptions associated with hyperglycemia. The impact of such effects could influence quality of life and daily functioning, as well as indicate cues to aid patients in better recognizing the presence of hyperglycemia. Holmes et al. (1) reported significant slowing of visual reaction time during a hospital clamp study at a blood glucose level of 16.7 mmol/l but were unable to replicate this subsequently using an auditory reaction-time task (2). Davis et al. (3) reported that blood glucose in the 20-to 30-mmol/l range was associated with a 9.5% reduction in type 1 diabetic children's performance IQ. Performance IQ was worsened in 67% of the children studied. Summerfield et al. (4) used a hyperinsulinic glucose clamp to test cognitive functioning at 14.5 and 16 mmol/l in adults with type 2 diabetes. During hyperglycemia, significant disruptions occurred in the performance of complex tests of cognitive functioning, such as four-choice reaction time. However, other investigators (5,6) were unable to detect decay in cognitive-motor performance on selected neuropsychological tests during hyperglycemia.Contrary to hypoglycemia and its associated neuroglycopenia, a major barrier to the investigation of the effects of hyperglycemia on cognitive-motor performance is the absence of a clear physiological mechanism that explains how hyperglycemia negatively influences brain functioning. However, research suggests several possible mechanisms (6).

Hyperglycemia alters E-NTPDases, ecto-5′-nucleotidase, and ectosolic and cytosolic adenosine deaminase activities and expression from encephala of adult zebrafish (Danio rerio)

“…Our results demonstrated that ecto-ADA activity was significantly increased in 111-mM glucose group, suggesting a decrease in adenosine levels in synaptic cleft. There is some consensus that a decrease of adenosine levels could be related with cognitive impairment observed in diabetic rats [8,55,56], which also could be suggested occurring in the zebrafish hyperglycemic model.…”

Cognitive dysfunction associates with white matter hyperintensities and subcortical atrophy on magnetic resonance imaging of the elderly diabetes mellitus Japanese elderly diabetes intervention trial (J‐EDIT)

“…However, the results of our study do not support the notion of any relationship between cognitive dysfunction and diabetic clinical characteristics. Whether variations in glucose homeostasis influence cognitive function remains controversial [49][50][51], although it has been found that the cognitive function of diabetic and nondiabetic subjects fluctuates in accordance with the serum glucose levels [50,51]. At the same time, increased insulin resistance is associated with atrophy of medial temporal lobe structures in elderly diabetic patients [52].…”

Redução da mobilidade funcional e da capacidade cognitiva no diabetes melito tipo 2

“…Evidências apontam para a relação positiva entre DM2 e declínio cognitivo, o qual também está implicado na inabilidade motora, devido ao comprometimento da atenção, da memória e de respostas protetoras, apraxia, desorientação espacial e deterioração das funções executivas e motoras (marcha alterada, desequilíbrio, instabilidade postural, alteração de tônus muscular); além do fato de os pacientes com essas condições não poderem julgar adequadamente sua própria capacidade, tomando atitudes arriscadas que levam a acidentes (7). Os défi-cits cognitivos, quando somados à presença de hiperglicemia, também podem aumentar a incapacidade física, trazendo dificuldades na realização de atividades da vida diária (AVD).…”

“…Entretanto, pouco se sabe sobre a relação entre distúrbio cognitivo e incapacidade física nos pacientes com DM2 (8). Estudos prévios sugerem que a alteração cognitivo-motora pode não apresentar uma relação linear com a glicemia, mas sim que pode haver um limite por volta de 270 mg/dL a partir do qual a função cognitivo-motora começaria a ser afetada (7). Embora se saiba a respeito da hipoglicemia e sua neuroglicopenia, um dos principais obstáculos para a investigação dos efeitos da hiperglicemia sobre o desempenho cognitivo-motor é a ausência de um mecanismo fisiológico claro que explique sua influência negativa sobre o funcionamento cerebral.…”