Developmental Trajectory of Hypoglycemia’s Impact on Cognition and the Brain

Tamara Hershey, Ph.D.

Washington University School of Medicine, St. Louis, MO

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

September 2002, for 3 years

Funding Amount:


Lay Summary

Does New Intensive Treatment for Juvenile Diabetes Affect Cognitive Development?

Juvenile (Type I) diabetes is an autoimmune disease in which the child’s immune system identifies pancreatic cells as foreign” and attacks them, making them less able to rid the body of excess sugar.  The newest treatment strategy of intensive therapy greatly reduces sugar levels, which has significant benefits for controlling diabetes in these children.  While some researchers consider the consequences of this severe hypoglycemia (low sugar level) to be negligible, the investigators hypothesize that it may present an increased risk for damage to the hippocampus, a region particularly sensitive to metabolic insults.  They predict that the hippocampus will be smaller in children with a history of repeated severe hypoglycemia, and that this atrophy will correlate with reduced long-term memory function.  Additionally, they anticipate that damage will be greater in younger, compared to older, children due to interruption of critical developmental processes or increased susceptibility for neuronal impact.

The researchers propose to test this hypothesis using MRI scans and cognitive testing in children with diabetes and in healthy controls, all aged 8 to 14.  They would measure hippocampal volumes using MRI and long-term memory using cognitive tests, and would compare the results in diabetic children with severe hypoglycemia at the younger versus older ages and compare both of these groups to age-matched healthy controls.  If there is an effect, this finding would be an important contribution to informing difficult treatment decisions.

Investigator Biographies

Tamara Hershey, Ph.D.

Assistant Professor, Washington University School of Medicine



We hypothesized that severe hypoglycemia in children with type 1 diabetes would have a deleterious and specific effect on the hippocampus, a region particularly sensitive to metabolic insults, and on long-term memory, a skill that relies upon the integrity of the hippocampus.

The overall aim of this project was to determine the effects of severe hypoglycemia, a particularly common complication in children with T1DM, on the hippocampus and memory skills. We assessed this risk in a hypothesis-driven manner using sensitive structural neuroimaging techniques and selective experimental cognitive tools.

The power of modern structural neuroimaging data collection and analysis techniques and experimental cognitive tools were brought to bear on these issues. We used high resolution structural neuroimaging techniques to acquire brain images in children with T1DM and controls and tested memory with sensitive cognitive neuroscience tools.

We found that hypoglycemia affected memory, but did not affect the hippocampus in the expected manner. We were able to use this information to obtain a larger grant from NIH. With this larger award, we have been able to examine other parts of the brain. Current results indicate that prior hypoglycemia and hyperglycemia was related to changes in specific regions of gray and white matter in the cortex. We are now following these youth prospectively to determine how these regions respond to further exposure to glycemic extremes and how they relate to cognitive changes in T1DM.

Selected Publications

Hershey T., Perantie D.C., Warren S.L., Zimmerman E.C., Sadler M., and White N.H.  Frequency and timing of severe hypoglycemia affects spatial memory in children with type 1 diabetes.  Diabetes Care. 2005 Oct;28(10):2372-7 .

Lyons-Warren A., Lillie R., and Hershey T.   Short and long-term spatial delayed response performance across the lifespan.  Dev Neuropsychol. 2004;26(3):661-78 .