Having COVID-19 appears to drastically increase the risk of death in people hospitalized for diabetic ketoacidosis (DKA) — a life-threatening condition in which high blood glucose levels lead to toxic levels of chemicals called ketones in the bloodstream — according to a new study published in the journal JAMA Network Open.
The study’s authors noted that even though rates of hospitalization for diabetic ketoacidosis have gone up in recent years, the age-adjusted death rate has actually gone down at the same time. This most likely reflects better treatment for DKA patients, people with less severe DKA seeking hospital care, or both. But the trend of lower hospital death rates for DKA appears not to apply to people with COVID-19, according to patient data from multiple hospitals in the United States.
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The effect of COVID-19 on DKA death risk
In the latest study, researchers used anonymous individual-level data on hospitalizations for DKA to look at the severity of the condition, how much insulin patients required, any complications that developed, and the rate of death during the hospital stay. The data came from 175 hospitals in 17 U.S. states and was collected from February 1 to September 15, 2020. Every single patient, in each of the 175 hospitals, received insulin according to the same computerized program, so insulin requirements reflected their actual health condition rather than the judgment of any healthcare providers.
The researchers found that our of a total of 5,029 patients with DKA during the study period who were treated with insulin for at least four hours, 210 (4%) tested positive for COVID-19 while 4,819 (96%) tested negative. Those with COVID-19 tended to be older, with an average age of 56 compared with 47 for those without COVID-19. They also tended to have a higher body-mass index (BMI, a measure of body weight that takes height into account), with an average BMI of 31 compared with 28 for those without COVID-19. Not surprisingly, older patients with DKA and COVID-19 — those over age 65 — were more likely to have diabetes complications or cardiovascular disease than those younger than 65.
But the researchers also found that at the time of hospital admission for DKA, blood glucose and A1C (a measure of long-term glucose control) levels were similar between people with and without COVID-19. These similarities in blood glucose control didn’t translate, though, into a similar rate of complications or death during the hospital stay. While only 5% (262 out of 4,819) of DKA patients without COVID-19 died, 30% (64 out of 210) of those with COVID-19 died during their hospital stay. While 30% of those with COVID-19 developed acute kidney injury in the hospital, only 10% of those without COVID-19 did the same. The risk of death was higher in older patients both with and without COVID-19, climbing to 45% (33 out of 73) for those over age 65 with COVID-19 and 13% (110 out of 860) for those over age 65 without COVID-19.
The higher risk of death associated with COVID-19 also applied to younger people hospitalized for DKA, those under age 45. For those with COVID-19, the death rate in this age group was 19% (10 out of 54), while it was only 2% (41 out of 2,290) for those without COVID-19. Even among patients who didn’t die or develop serious complications, having COVID-19 resulted in overall higher insulin requirements and a longer duration of insulin treatment, along with a longer duration before DKA was resolved.
Despite these clear differences based on COVID-19 status, the researchers noted that “the cause for the considerably higher mortality in the COVID-19–positive population is unknown.” Contributing factors, they wrote, might include a higher rate of obesity and a more severe overall stress state, as indicated by higher insulin requirements. “These findings are worrisome and warrant further investigation,” the researchers concluded.
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