Author: Maya Palmer, PharmD. Candidate, Florida A&M University College of Pharmacy
Exposure to glycemic extremes has been shown to negatively impact healthy brain development and cognitive function, including spatial working memory.
The brain is a complex organ; in childhood and adolescent development, it undergoes a lot of rapid changes and synaptic pruning. With type 1 diabetes in this population, however, a child could be exposed to extended periods of severe hyperglycemia before official diagnosis, and insulin treatment, is rendered. This exposure to glycemic extremes has been shown to impact healthy brain development and even cognitive function negatively. This open-label study dives into investigating the effects of acute hyperglycemia on spatial working memory in adolescents with type 1 diabetes.
For this trial, researchers looked at outcomes from the difference in spatial working memory (sWM) capacity during acute hyperglycemia compared with euglycemia in adolescents with type 1 diabetes. One group of participants were aged between 11 and 19 years old, had type 1 diabetes between 5 and 10 years, and had not experienced a severe hypoglycemic episode or diabetic ketoacidosis within the last year. An intravenous euglycemic clamp was started on these participants, along with MRI spectroscopy performed. Every 15 minutes, blood glucose concentrations were measured and maintained between 90 and 180 mg/dL. Once completed, levels were raised by an intravenous glucose bolus, and a hyperglycemic clamp was kept between 270 and 450 mg/dL for two hours.
The other group of participants without type 1 diabetes followed the same protocol; however, they did not have any glycemic manipulations. The Sternberg item-recognition task was used to observe short-term and working memory among both groups. Differences and effects of induced hyperglycemia on sWM capacity estimates were assessed with a two-way mixed-design ANOVA test. Researchers also collected neuroimaging data—mostly images concurrent with sWM task performance. Functional data were analyzed according to selected regions of interest (ROIs) of the brain involved in forming spatial information. Within the frontal cortex, ratios of magnetic resonance surface areas of N-acetyl aspartate, choline, and creatine were assessed and compared between each group after the MRI sessions.
The number of retained positions in the sWM task showed a substantial decrease in the amount of successfully retained positions (P = 0.048) among the group of adolescents with type 1 diabetes. Findings from the MRI spectroscopy showed a significant decrease of N-acetyl aspartate, choline, and creatine (P < 0.01, P <0.005, and P < 0.01, respectively) after the hyperglycemia clamp in the adolescent cohort with type 1 diabetes. Researchers noticed that this significantly correlated with the increase in blood glucose levels. The reduced sWM capacity in adolescents with type 1 diabetes during acute hyperglycemia provided evidence that supported observations from a previous study conducted with young children (ages 4 to 10). This study examined the impact of dysglycemia on neuroanatomical growth and cognitive development on children with and without type 1 diabetes. The group with type 1 diabetes had significant differences in total and regional gray and white matter growth within critical brain regions involved in sensorimotor processing and cognition. Data from this related study also suggested that chronic hyperglycemia was detrimental to the developing brain of young children with type 1 diabetes.
This particular study was the first to provide evidence of acute hyperglycemia having direct effects on sWM. The study used restricted magnetic resonance imaging; therefore, results could have possibly been related to other factors as well, like the reduction of metabolites in the frontal cortex during hyperglycemia or even hyperglycemia effects on the blood-brain barrier. The study was single-centered and only included a small number of participants, limiting the amount of available data. Overall, nonetheless, the impact of acute hyperglycemia on sWM confirmed that it could be a direct indicator of school engagement and other cognitive challenges in the adolescent population with type 1 diabetes.
Practice Pearls:
- Teens with type 1 diabetes showed a significant decrease in performance of the Sternberg item-recognition task compared to the group without type 1 diabetes.
- A reduction of N-acetyl aspartate, choline, and creatine was found after the hyperglycemia clamp in adolescents with type 1 diabetes.
- This study was the first to show acute hyperglycemia negatively impacting sWM in teenagers with type 1 diabetes.
Omladič, Jasna Šuput, et al. “Acute Hyperglycemia and Spatial Working Memory in Adolescents with Type 1 Diabetes.” 2020, doi:10.2337/figshare.12152181.v1.
Ryan, Christopher M. “Cognition in Children and Adolescents with Type 1 Diabetes.” Diabetes and the Brain, 2009, pp. 251–275., doi:10.1007/978-1-60327-850-8_10.
Mauras, Nelly, et al. “Longitudinal Assessment of Neuroanatomical and Cognitive Differences in Young Children With Type 1 Diabetes: Association With Hyperglycemia.” Diabetes, vol. 64, no. 5, 2014, pp. 1770–1779., doi:10.2337/db14-1445.
Maya Palmer, PharmD. Candidate, Florida A&M University College of Pharmacy
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