News & Research

University of California Davis Medical Center Sacramento, California

Cerebral edema and cerebral injury in pediatric diabetic ketoacidosis

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Other, Pediatrics\Type 1

Type of Grant: Basic Science

Project Start Date: January 1, 2009

Project End Date: June 30, 2012

Research Description

Funded by the Order of the Amaranth

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes which may occur at onset of diabetes, or during episodes of illness.  During DKA, blood glucose levels are high and fat breaks down rapidly, resulting in high levels of fat breakdown products (ketones).  Although most children recover from DKA, approximately 1% develop cerebral edema (brain swelling), which often causes permanent brain damage or death.  DKA-related cerebral edema is the most frequent diabetes-related cause of death in children.  Previous studies by our group suggest that cerebral edema may result from poor blood flow to the brain during DKA.  Our data suggest that even a modest decrease in brain blood flow may cause brain injury, if this decrease occurs under the conditions present during DKA (elevated blood glucose and ketone levels and acidosis). 

Exactly why the conditions of DKA increase the damaging effects of a reduction in brain blood flow is not known.   In our proposal, we aim to investigate which of the metabolic alterations occurring during DKA predispose children to brain injury and brain swelling.   We plan to induce various metabolic alterations in rats to determine which factor, or combination of factors, leads to brain swelling.  These data will allow us to develop a more complete understanding of the mechanisms responsible for cerebral edema and to determine which treatments might be used to prevent cerebral edema.   In addition, data from the proposed studies are applicable to other common conditions which may affect individuals with diabetes, such as stroke and head trauma.

Reseacher Profile

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes? 

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes which may occur at onset of diabetes, or during episodes of illness.  During DKA, blood glucose levels are high and fat breaks down rapidly, resulting in high levels of fat breakdown products (ketones).  Although most children recover from DKA, approximately 1% develop cerebral edema (brain swelling), which often causes permanent brain damage or death.  DKA-related cerebral edema is the most frequent diabetes-related cause of death in children.  Previous studies by our group suggest that cerebral edema may result from poor blood flow to the brain during DKA.  Our data suggest that even a modest decrease in brain blood flow may cause brain injury, if this decrease occurs under the conditions present during DKA (elevated blood glucose and ketone levels and acidosis). 

Exactly why the conditions of DKA increase the damaging effects of a reduction in brain blood flow is not known.   In our proposal, we aim to investigate which of the metabolic alterations occurring during DKA predispose children to brain injury and brain swelling.   The data gathered in our study will allow us to develop a more complete understanding of the mechanisms responsible for cerebral edema and to determine which treatments might be used to prevent cerebral edema in children with DKA.   In addition, data from this study might help us to better understand other common conditions, such as stroke and head trauma, which may affect people with diabetes.  The data will help us to determine how best to help individuals with diabetes recover from these conditions. 

If a person with diabetes were to ask you how your project will help them in the future, how would you respond? 

Even individuals who are very careful about their diabetes care can develop diabetic ketoacidosis (DKA) in some situations, especially during episodes of illness.  In addition, people with new onset of diabetes often have DKA at the time of diagnosis, especially children.  DKA can cause injury to the brain, but the mechanism behind this injury is not well understood.  The data gathered in our project will help us learn how best to help people with diabetes recover from DKA without damage to the brain.   In addition, our project will help us to understand how different factors affect the brain in people with diabetes.   

At present, we do not have a good understanding of how high glucose concentrations, elevated blood ketone concentrations and other factors affect the brain's blood flow and metabolism.  These studies will help us to gain a broader understanding of the effects of metabolic changes resulting from diabetes on the brain and will help us to learn how best to help people with diabetes recover from other brain injuries such as stroke or traumatic injuries. 

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts? 

When I was doing my residency training in pediatrics, a beautiful 2 year old boy was admitted to the pediatric intensive care unit with cerebral edema (brain swelling) resulting from diabetic ketoacidosis.  Tragically, he did not survive the episode.  Disheartened by the tragedy of this child's death, I searched the medical literature to try to better understand why this had happened to him and whether there was anything that could have been done to prevent it.   I was surprised to find out how little was understood about how diabetic ketoacidosis effects the brain and why cerebral edema sometimes occurs.  The sense that there was a gap in our understanding of diabetic ketoacidosis stayed with me through my residency training in pediatrics and my fellowship in pediatric endocrinology.  

When it came time to choose a research path, it was clear to me what my path should be.  For the past 10 years, I have been studying the effects of diabetic ketoacidosis on the brain.  We now have a large, multi-disciplinary group working on projects aimed at understanding the changes in brain metabolism and blood flow that occur during DKA and how best to prevent brain injury in this setting.  The current award will allow us to further study the basic mechanisms underlying brain injury in DKA with the ultimate goal of preventing brain damage or death in children with DKA.  

In what direction do you see the future of diabetes research going? 

For type 1 diabetes, I am hopeful that the future will allow for early detection of the immune system abnormalities responsible for causing the disease and intervention at that stage to prevent type 1diabetes from occurring.  Early studies indicate that this could be possible in the future.  It would be a joy to be able to see type 1 diabetes become a condition of the past.