NEW ORLEANS – Recurrent episodes of diabetic ketoacidosis (DKA) resulted in altered brain metabolite concentration, as well as differences in mental processing speed, compared with healthy controls, judging from the results from a small pilot study.
While previous work examining the relationship of DKA to cognition and neural structure has focused upon children and adolescents, researchers at Emory University and the Georgia Institute of Technology, both in Atlanta, set out of evaluate for the first time acute neuroanatomical and cognitive changes in adult patients with first and recurrent episodes of DKA. In an interview in advance of the annual scientific sessions of the American Diabetes Association, one of the researchers, Gilda E. Ennis, Ph.D., said that DKA is the most serious diabetic emergency in patients with type 1 and 2 diabetes and results in an estimated health care cost of $2.4 billion annually. “While we know that one of the major precipitating causes of DKA in adult patients is poor adherence to insulin therapy, we do not understand why patients are noncompliant,” said Dr. Ennis, who is a postdoctoral fellow in the Georgia Institute of Technology’s school of psychology.
Dr. Gilda Ennis
She and her associates conducted a pilot study examining advanced MRI metrics and cognitive measures 72 hours after resolution of DKA in 10 patients with a first episode of DKA and 11 patients with three or more episodes of DKA. The same MRI and cognitive measures were collected from 10 healthy controls and 10 patients with type 1 diabetes and no history of DKA.
MRI spectroscopy revealed reduced N-acetylaspartate concentrations in diabetes patients with multiple episodes of DKA, compared with healthy controls, but no significant differences were seen between diabetes patients with and without DKA. Cognitive testing revealed that patients with recurrent DKA had significantly worse processing speed, compared with healthy controls (P = .02), while processing speed deficits in patients with a single DKA and those with diabetes and no DKA was intermediate between healthy controls and those with recurrent DKA.
“We were surprised to find significant cognitive and neural deficits in the recurrent DKA group relative to healthy controls in such a small sample,” Dr. Ennis said. “This suggests that statistical differences in cognition and neural structure between patients with recurrent DKA and healthy controls may be large. We found that recurrent DKA was associated with significant deficits in processing speed and memory, decreases in right putamen volume, regionally decreased white matter integrity, and altered brain metabolite concentrations, suggestive of CNS inflammatory changes and neuronal injury.”
The findings may explain the high rates of medication noncompliance commonly seen in this patient population. “If this proposition is true, conventional education and standard care approaches to the treatment of type 1 diabetes, especially in patients with a history of DKA, may need to change,” she said. “Strategies to improve insulin adherence may require a special insulin compliance intervention that includes persistent medication adherence reminders, such as text messaging and nurse-telephone follow-up.”
Dr. Ennis acknowledged that the findings require replication in a prospective longitudinal study with a larger sample size. “It will be important to determine if acute neuroanatomical and cognitive deficits in patients with recurrent DKA persist over time,” she said. “Duration of type 1 diabetes could produce similar findings and would need to be controlled in future research.” She reported having no financial disclosures.