Ketoacidosis in Kids With Type 1 Diabetes Tied to Worse Memory, IQ

Marlene Busko

October 15, 2020

Children who had a single episode of moderate/severe diabetic ketoacidosis (DKA) and were newly diagnosed with type 1 diabetes had a subtle decline in a long-term memory task when they were tested a few months later in a new study.

And other children with a known diagnosis of type 1 diabetes who had repeated DKA episodes had a sizable decline in IQ, "suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia," the authors write.

"Diabetes care providers have worried primarily about hypoglycemia as a risk factor for cognitive decline," lead author Simona Ghetti, PhD, told Medscape Medical News in an email.

However, "more recent data have underscored that hyperglycemia may be more important."

The "current data are the first to show that not only is chronic hyperglycemia important, but exposure to DKA is also very important," stressed Ghetti, professor of psychology at University of California, Davis.

Ghetti and colleagues publish their findings in Diabetes Care.

"Need More Focus on Preventing DKA"

According to Ghetti, this latest research shows that clinicians need to focus more on preventing DKA.

"A common practice is to have families try and monitor mild DKA at home and only go to the [emergency department (ED)] if DKA seems unlikely to be resolved at home," she noted. "Our findings might encourage diabetologists to send patients to the ED with milder DKA."

"Conversely, ED providers should also focus more on making sure mild DKA is fully resolved (or unlikely to worsen) before sending anyone home."  

And to prevent DKA in children and adolescents who may not realize they have type 1 diabetes, we need to "increase community understanding of the early signs of type 1 diabetes before DKA occurs," according to Ghetti.

"Some of these signs are not specific (eg, irritability, weakness) and could be mistaken for flu-like symptoms, but others are more telling such as increased thirst, frequent urination, [and] increased hunger but weight loss."

Among children already diagnosed with type 1 diabetes, she continued, the risk of DKA can be reduced by improving diabetes control.

This includes monitoring blood "glucose levels frequently to ensure that they are as stable as possible (blood sugar levels before meals between 80 and 130 mg/dL and after-meal numbers no higher than 180 mg/dL [10 mmol/L] 2 hours after eating)."

"Kids should also learn how to count carbs, fats, and proteins in their meals to make better predictions about their glucose levels," she noted.

Similarly, senior study author Nicole S. Glaser, MD, professor of pediatrics at UC Davis Health, said: "The results from the study emphasize the importance of prevention of DKA in children with known type 1 diabetes and of timely diagnosis during new onset before the development of DKA." 

"There is an opportunity to prevent DKA with proper management of the glucose level in the blood," she observed in a press release from her institution.

Impact of DKA on Cognition May Accumulate Over Time

Children with known type 1 diabetes may have an episode of DKA as a result of poor adherence to insulin regimens, illness, or malfunction of an insulin pump, and in other children, DKA may be the first symptom that leads to a diagnosis of type 1 diabetes, the investigators explain.

DKA is associated with changes in memory, attention, verbal intelligence quotient, and brain microstructure, but it was previously unclear how these effects may differ between children with new-onset versus longstanding type 1 diabetes.

The team analyzed data from 758 children and adolescents aged 6 to 18 who presented with DKA in 2011 to 2016 and were enrolled at multiple sites that participated in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) randomized clinical trial that compared four rehydration protocols to treat DKA.

Of these study participants, 430 had moderate or severe DKA, 328 had mild DKA, while approximately half (n = 392) had new-onset type 1 diabetes, and the remainder (n = 366) had been previously diagnosed with type 1 diabetes.

A comparison group of 376 children with type 1 diabetes but no DKA were also enrolled.

The participants had a neurocognitive assessment 2 to 6 months after the DKA episode, which included an item-color (spatial memory) task that evaluated long-term memory; the Wechsler Abbreviated Scale of Intelligence (IQ test); and the digit span forward and backward task that evaluated short-term and working memory.   

Overall, moderate/severe DKA was associated with lower IQ (P < .001) and lower scores on the item-color recall score (P = .01) and forward digit-span tasks (P = .04).

Among participants with newly diagnosed type 1 diabetes, moderate/severe DKA was associated with lower scores on the item-color recall test (P = .04).

And among previously diagnosed patients, repeated DKA exposure and higher A1c levels were independently associated with a lower IQ (P < .01), and higher A1c was also associated with a lower item-color recall score (P = .007) after correcting for hypoglycemia, diabetes duration, and socioeconomic status. 

"We think that these decreases [in cognitive function] are long-lasting and may accumulate and be stronger over time," said Ghetti.

The deficits "may be subtle at first, but over time they may become sizeable. For example, among previously diagnosed patients, there was a difference of about 8 IQ points between children who experienced DKA and children who did not. That is over half of a standard deviation difference which would be considered clinically significant."

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and partly funded by the Health Resources and Services Administration, Maternal and Child Health Bureau, and Emergency Medical Services for Children. The authors have reported no relevant financial relationships.

Diabetes Care. Published online September 22, 2020. Abstract

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