Diabetic Ketoacidosis and Brain Function
Diabetic Ketoacidosis (DKA) is a life-threatening consequence of diabetes. DKA occurs when there is a lack of insulin in the body causing hyperglycemia. As a result of the inability of glucose to enter the cells, the body must find other means to obtain energy. As such, fat breakdown occurs resulting in the accumulation of fatty acids. The fatty acids are metabolized to ketones that cause the blood to become acidotic (pH less than7.3). Because glucose remains in the blood, there is an increase in thirst and drinking to eliminate the solute load of glucose, which also results in increased urination (polyuria and polydipsia). Thus, the combination of increased serum acidity, weight loss, polyuria, and polydipsia may lead to extreme dehydration, coma, or brain damage.
Without a doubt, the most severe acute complication of DKA is cerebral edema. Many cases of new onset type 1 diabetes present DKA (15-70 percent depending on age and geographic region, according to multiple studies), hence the importance of an early diagnosis of diabetes in order to avoid potential consequences.
Much research is being conducted to predict the development of severe complications of DKA, most notably on brain herniation, the swelling of the brain that causes it to push towards the spinal cord, as well as other neurological consequences. Fulminant cerebral edema, or swelling of the brain, is relatively rare and has an incidence rate of 0.5-0.9 percent. However, what about the subtler, less severe alterations in brain functions that occur after DKA?
Indeed, a recent paper published in Diabetes Care 2014; 37: 1554-1562by Cameron, Scratch, Nadebaum, Northum, Koves, Jennings, Finney, Neil, Wellard, Mackay, and Inder on behalf of the DKA Brain Injury Study Group entitled "Neurological Consequences of Diabetic Ketoacidosis at Initial Presentation of Type 1 Diabetes in a Prospective Cohort Study of Children" discusses the "impact of new onset DKA during childhood" on brain structure and function. The authors hypothesized that "just as there exists a continuum of clinical and subclinical cerebral edema there is also a continuum of brain injury in DKA and that the brain injury outside the context of cerebral edema is more common than previously recognized."
What were the methods of the study?
- Patients 6-18 years old with and without DKA at diagnosis
- Study timeframe used four time points post-diagnosis at:
- Less than 48 hours
- Five days
- 28 days
- Six months
- Patients received MRI and spectroscopy along with cognitive assessment at each time point
- Relationships between clinical characteristics at presentation, MRI results, and neurological outcomes were then evaluated using diverse statistical methods
What were the results of the study?
- 36 DKA and 59 non-DKA patients were recruited between 2004-2009
- In patients with DKA, "cerebral white motor showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal and parietal white mater."
- Total white matter volume decreased over the first six months
- In patients with DKA, gray matter volume was lower at baseline and increased over six months
- Lower levels of N-acetylaspartate were noted at baseline and at five days
- Most importantly, although changes in "total and regional brain volumes over the first five days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months"
- Age and time of presentation and pH level were predictors of neurological imaging evaluation and functioning
What may be learned from the study?
DKA at type 1 diagnosis results in structural and functional brain changes based on neurological imaging and functional evaluations. In addition, these changes are associated with adverse "neurocognitive" outcomes in the medium term. Thus, brain injury resulting from DKA should no longer be considered a rare complication.
As such, The Pediatric Emergency Care Applied Research NetworkFLUID’s (Fluid therapies Under Investigation in DKA) study in Pediatric Diabetes 2013: 14: 435-446 by Glaser et. al. and the PECARN study group is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. The 13-center nationwide design including our center at Children’s National Health System, will evaluate the effects of rehydration rate and fluid sodium content on neurological status during the DKA treatment and the frequency of clinically overt cerebral edema and long-term neurocognitive outcomes from DKA.
Thus, it is hoped that fluid rehydration choices in DKA will also assist in determining best practices by preventing cerebral edema and long-term neurological and functional problems.
More to come on this subject".
Fran Cogen, M.D., C.D.E., is the director of the Childhood and Adolescent Diabetes Program at Children’s National Health System. She wrote about diabetes for HealthCentral.