DKA rates decrease after 7-year rise
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Incidence rates of diabetic ketoacidosis in the U.S. decreased by an average of 6.1% in 2018 and 2019 after increasing from 2011 to 2017, according to a study published in the Journal of Diabetes and Its Complications.
“This study provides up-to-date estimates of incidence of DKA and its trends in a large U.S. commercially insured population with type 1 diabetes over a study period of 13 years, with implications for care planning and drug development,” Lin Li, MD, PhD, a pharmacoepidemiologist at Sanofi in Bridgewater, New Jersey, and colleagues wrote. “The data reaffirmed that the incidence of DKA was higher in the pediatric and female populations. Furthermore, the data showed that age-sex-standardized incidence of DKA significantly decreased during 2018-2019 after a steady increase since 2011.”
Researchers conducted a retrospective cohort study analyzing patient data from the IBM MarketScan database. Data on U.S. residents of all ages with type 1 diabetes were obtained from 2007 to 2019. Researchers extracted hospitalized DKA events occurring any time from index data to the end of follow-up. Consecutive DKA occurrences were considered distinct events if they were separated by at least 14 days.
The study included 455,423 people with type 1 diabetes (mean age, 38.9 years). The mean follow-up time was 2.7 years. The overall incidence rate of DKA from 2007 to 2019 was 55.5 cases per 1,000 person-years. The rate was higher for women and girls (62.9 cases per 1,000 person-years) compared with men and boys (48.6 cases per 1,000 person-years). Youths aged 10 to 19 years had the highest DKA incidence rates of any age group for both sexes, whereas adults aged 80 years or older had the lowest rates of any age group for both sexes.
After adjusting for age and sex, incidence rates of DKA decreased by a mean annual rate of 4% from 2007 to 2010, falling from 64.6 cases per 1,000 person years in 2007 to 54.1 per 1,000 person-years in 2010. From 2011 to 2017, DKA rates increased at an average annual rate of 2.9%, topping out at 67.3 cases per 1,000 person-years in 2017. DKA incidence rates fell by an average of 6.1% in the final 2 years of the study to 65.2 cases per 1,000 person-years in 2018 and 60.4 cases per 1,000 person-years in 2019.
“Although the causes for the increase in 2011-2017 are unclear, several possible explanations have been proposed, including changes in DKA case definition, increased hospitalization for mild DKA cases, and new antihyperglycemic medications that might increase the risk of DKA, such as sodium-glucose cotransporter 2 inhibitors,” the researchers wrote. “The triggers for the decrease in 2018-2019 are also unclear.”
The researchers said more study is needed to see whether the decrease in DKA cases continued in 2020 and how much of an impact the COVID-19 pandemic has on DKA trends.
Perspective
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Helena W. Rodbard, MD, FACP, MACE
A recent report from Li and colleagues examines the incidence of diabetic ketoacidosis in people with type 1 diabetes from 2007-2019 based on a large dataset describing claims arising in the privately insured community. The authors observed a 16% steady decline in age- and sex-standardized incidence of DKA between 2007 and 2010, followed by a 25% increase between 2010 and 2017, and then an 11% decline between 2017 and 2019. The study does not permit us to assign mechanisms for these trends.
These changes are very modest: The age- and sex-corrected incidence in 2019 was lower than in in 2007. Many possible mechanisms may be at play. The criteria for DKA may have changed, or the actual practice of reporting ICD codes may have changed. The authors did not examine the incidence of the original diagnosis of type 1 diabetes. DKA is often a presenting symptom of onset of type 1 diabetes, so a correction for that possibility should have been included.
The authors do not discuss the fact that the most important finding in their analysis is the very high risk for DKA in the age group from 0 to 29 years, with the highest frequency in the age group 10 to 19 years, and with the risk for girls being 20% to 50% higher than for boys for each age group. Between the ages of 30 to 80 years and older, the incidence of DKA drops off by a factor of 12 in men and 13 in women. This is consistent with DKA being associated with the onset and initial diagnosis of type 1 diabetes.
The authors speculate on possible reasons for the increase in incidence of DKA between 2010 and 2017. Based on a report from Benoit and colleagues (MMWR Morb Mortal Wkly Rep. 2018;doi:10.15585/mmwr.mm6712a3.), Li and colleagues speculate that the increase might be due to the appearance of new forms of therapy such as SGLT2 inhibitors that might increase the risk for DKA. That speculation appears to be entirely without merit as Benoit and colleagues had espoused the opposite point of view in 2018, stating that “because SGLT2 inhibitors were only recently approved, and DKA rates increased before their introduction, they are likely not a major contributor to the increasing DKA trend.” Of note is the fact that SGLT2 inhibitors are not approved for the treatment of people with type 1 diabetes, and they have not been widely used off label. Accordingly, I would regard the speculation of Li and colleagues that increasing use of SGLT2 inhibitors might have been responsible for an increased incidence of DKA in people with type 1 diabetes as being entirely unfounded.
On a positive note, the incidence of DKA in people with type 1 diabetes has decreased steadily from 2017 to 2019, as noted by the authors.
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