This article is more than 5 years old. Information may no longer be current.
Upcoming study will target optimal treatment of diabetic ketoacidosis
Click Here to Manage Email Alerts
A husband-and-wife research team was awarded a 5-year, $3.3 million grant to conduct a prospective, multicenter clinical study of the prevention of neurological injuries and death in children with diabetic ketoacidosis.
Nicole Glaser, MD, associate professor of pediatric endocrinology, and Nathan Kuppermann, MD, MPH, professor of emergency medicine and pediatrics, both at University of California, Davis, will lead the study, which is slated to begin in the fall. The study will enroll about 1,500 children who will be randomly assigned to one of four groups and receive different rates of rehydration with varying sodium content. Mental status will be monitored hourly for signs of cognitive decline and brain swelling. Older children will be re-evaluated at 3 months with memory and IQ tests. The researchers will then assess the effects of fluid infusion rates and their sodium content on the risks for short- and long-term neurological injury.
“This type of study has never been conducted before, not even in a smaller sample,” Glaser told Endocrine Today. “A prospective, randomized clinical study such as this is the gold standard for determining the best way to rehydrate children with diabetic ketoacidosis.”
It is estimated that about 1% of children with diabetic ketoacidosis develop serious brain swelling, and about one-quarter of them die as a result. More subtle neurological injuries resulting from diabetic ketoacidosis, such as memory problems, are much more common, according to the researchers.
“The topic of fluid rehydration rate in children with diabetic ketoacidosis is one of the pressing and lingering issues in the management of these patients. With this study, we hope to help resolve this conundrum,” Kuppermann said.
Evaluation of current approaches
Current approaches to treating diabetic ketoacidosis in children are diverse, and the data are expected to provide a clearer picture of the best method of alleviating diabetic crisis.
The study will evaluate opposing theories of fluid treatment and the effects on neurological outcomes.
Glaser said there are strong arguments for aggressive vs. conservative fluid resuscitation, and she has no preconceived notion regarding the yet-to-be-determined results.
“Until now, the debates have been based in theory and our knowledge of physiology. Guidelines are fairly general and allow for quite a bit of variation in the rate of fluid replacement and sodium content,” she said. “We hope that this study will provide the definitive data that have been missing for years and will be able to guide and standardize clinical care.”
The issue of hydration is just one aspect of the treatment of diabetic ketoacidosis, Kupperman said, adding that it has never been investigated in such a comprehensive and rigorous way.
Intersecting research
Glaser and Kuppermann have collaborated on many studies pertaining to diabetic ketoacidosis in children during the past decade.
“As a pediatric emergency physician and a pediatric endocrinologist, the place that our worlds intersect is diabetic ketoacidosis,” both Glaser and Kuppermann said. “Our joint interest in the area has had us working together through various, different types of studies — some clinical epidemiological, others more lab-based, and many involving sophisticated MRI techniques.”
Their study published in The New England Journal of Medicine in 2001 found that treatment with sodium bicarbonate may increase the risk for cerebral edema in children with diabetic ketoacidosis. Glaser was the co-author of a study published in Pediatrics in 2009 that found that most children who have had an episode of diabetic ketoacidosis also have persistent memory problems.
The new study will be conducted at 10 study sites in addition to University of California, Davis. It will be funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and will be conducted through the Pediatric Emergency Care Applied Research Network. – by Matthew Brannon
Follow
EndocrineToday.com on Twitter.