Acute Hyperglycemia Impairs Spatial Working Memory in Adolescents With T1D

girl teenager measures blood sugar level
Acute hyperglycemia affects brain metabolite concentration and performance on spatial working memory tasks in adolescents with type 1 diabetes.

Acute hyperglycemia negatively affects spatial working memory in adolescents with type 1 diabetes (T1D), according to results of a study published in Diabetes Care.

In pediatric and adult patients, T1D has been shown to affect the structure and function of the brain. To investigate the correlation between acute hyperglycemia and spatial working memory in adolescents with T1D, data from 34 patients aged 11 to 19 years were analyzed. Included participants had a duration of T1D of 5 to 10 years and had not had a severe hypoglycemic episode or diabetic ketoacidosis within the previous year. Overall, 15 adolescents with T1D and 19 age-matched control participants were included.

After an overnight stay to maintain stable glycemia, individuals in the T1D group received a euglycemic clamp and performed a spatial working memory task while undergoing a functional magnetic resonance imaging (fMRI) scan and MRI spectroscopy. Capillary blood glucose concentrations were measured every 15 minutes and maintained at 90 to 180 mg/dL (mean, 137±36 mg/dL). The scanning protocol was repeated while the participants with T1D received a hyperglycemic clamp and blood glucose concentrations were maintained at 270 to 450 mg/dL (mean, 362±43 mg/dL) through intravenous glucose bolus for 2 hours. Healthy age-matched individuals who did not have T1D followed the same experimental protocol without any changes made to their glycemic levels.

Whereas the spatial memory task performance of adolescents in the control group improved from the first to second session, the performance of adolescents with T1D worsened between sessions (P =.048). Activation of the a priori regions of interest, such as the medial temporal lobe, dorsolateral prefrontal cortex, medial intraparietal area, and anterior intraparietal region, decreased significantly in adolescents with T1D from the first to second session compared with a moderate increase in an overall lower activation from session 1 to session 2 in adolescents in the control group (P =.014).

Further analysis showed this difference in change in activation was significant for each phase of working memory (encoding, delay, and response) in both the left (P =.046) and right hemispheres (P =.016). Significant decreases in N-acetylaspartate (P <.01), choline (P <.005), and creatine (P <.01) were observed in the frontal cortex of participants with T1D after the hyperglycemic clamp compared with levels at euglycemia, and a correlation of blood glucose levels and N-acetylaspartate (P <.01), choline (P <.01), and creatine (P <.05) was observed in these patients. No significant change in metabolite levels were observed in the control group.

The results of this study suggested that acute hyperglycemia has a direct effect on spatial working memory. The significantly higher overall brain activation in adolescents with T1D during spatial working memory tasks, which may be a compensation mechanism for inefficient encoding, significantly decreased during hyperglycemia, which may have explained the significantly poorer performance in the T1D group compared with the control group. The significant decrease in metabolite concentrations may have been due to the effect of hyperglycemia on the blood-brain barrier and an increase in local water content.

Limitations to this study included its single-center design, small cohort, and limited magnetic resonance acquisitions. Future studies investigating other potential causes of impaired working memory in T1D are warranted.

Disclosure: One study author reported affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

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Omladič JS, Ozimič AS, Vovk A, et al. Acute hyperglycemia and spatial working memory in adolescents with type 1 diabetes [published online May 29, 2020]. Diabetes Care. doi:10.2337/dc20-0171