A husband-and-wife research team at the UC Davis School of Medicine has been awarded a five-year, $3.3 million grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to lead the first prospective, nationwide, multi-site clinical study of how to prevent the neurological injuries and, in rare cases, death caused by brain swelling in children in diabetic crisis.
Twenty-five to 40 percent of children with type-1 diabetes are diagnosed following an episode of diabetic crisis, or diabetic ketoacidosis, which occurs when the body releases acidic ketones into the blood as a byproduct of burning fat stores for energy. Symptoms of diabetic crisis include vomiting, fatigue, confusion and dehydration. Approximately 1 percent of children in diabetic crisis develop serious brain swelling, and about a quarter of them die as a result. However, more subtle neurological effects of diabetic ketoacidosis, such as memory problems, are much more common, the researchers said.
Nathan Kuppermann, professor of emergency medicine and pediatrics and chair of the Department of Emergency Medicine, and Nicole Glaser, associate professor of pediatric endocrinology, will lead the investigation into the potentially life-threatening condition, in collaboration with researchers at nine other medical centers around the country in the Pediatric Emergency Care Applied Research Network (PECARN). The team will enroll approximately 1,500 children in the study, which will examine the best way to rehydrate children in diabetic crisis in hospital emergency departments, in order to minimize adverse neurological outcomes.
“While it is only one aspect of the treatment of patients with diabetic ketoacidosis, the important issue of whether to rehydrate patients quickly or slowly has been debated for some time but never in such a comprehensive and rigorous way,” Kuppermann said.
The couple has been studying how to prevent brain swelling in diabetic ketoacidosis for more than a decade. Their research, published in 2001 in the New England Journal of Medicine, found that treatment with a solution of sodium bicarbonate contributed to adverse neurological outcomes in children with diabetic ketoacidosis.
Pediatric endocrinologist Glaser is co-author of a 2009 study published in the journal Pediatrics that found that most children who have had an episode of diabetic ketoacidosis also have persistent memory problems.
“Severe injury and death in diabetic ketoacidosis happens very rarely. But more worrisome is that much more subtle changes happen in many more children,” Glaser said. “That makes it all the more important to figure out the safest way to treat these children.”
The new study will be conducted through PECARN, which is funded by the Emergency Medical Services for Children Program within the Maternal and Child Health Bureau of the Health Resources and Services Administration.
In addition to UC Davis, the nine other study sites include:
- Nationwide Children’s Hospital in Columbus, Ohio
- Children’s National Medical Center, Washington, D.C.
- University of Utah, Salt Lake City
- Children’s Hospital of Philadelphia
- Columbia University, New York
- Children’s Memorial Hospital, Chicago
- Children’s Hospital of Boston
- Washington University and St. Louis Children’s Hospital
- Women and Children’s Hospital of Buffalo, N.Y.
Starting in the fall of 2010, 3- to 18-year-old children who are evaluated in participating emergency departments for diabetic crisis will be placed in one of four groups of study subjects. Each will receive different rates of rehydration with fluids with different levels of salinity. Researchers will assess participants’ mental status every hour while hospitalized, the appearance of any signs of cognitive decline and any overt symptoms of brain swelling. Older children will return for additional evaluation after three months, including testing of memory function and IQ. The researchers then will assess the effects of fluid infusion rates and their sodium content on the risks of both short- and long-term neurological injury.
“This type of study never has been done before, not even in a smaller sample,” Glaser said. “A prospective randomized clinical study like this really is the gold standard for determining the best way to rehydrate children with diabetic ketoacidosis.”
The UC Davis School of Medicine is among the nation’s leading medical schools, recognized for its specialty- and primary-care programs. The school offers fully accredited master’s degree programs in public health and in informatics, and its combined M.D.-Ph.D. program is training the next generation of physician-scientists to conduct high-impact research and translate discoveries into better clinical care. Along with being a recognized leader in medical research, the school is committed to serving underserved communities and advancing rural health. For further information, visit www.ucdmc.ucdavis.edu/medschool.
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UC Davis press release