MARCH 31 2021

Amy Reyes


Patients with diabetic ketoacidosis and a COVID-19 diagnosis died at increasingly higher rates than diabetic ketoacidosis patients without COVID-19, shows an analysis recently published in JAMA Network Open.

Published online March 10 as a research letter, physicians led by Francisco J. Pasquel, MD, MPH, of Emory University School of Medicine, Atlanta, conducted an analysis of data from the Glytec national database. The analysis included 5,029 patients with diabetic ketoacidosis who were treated at 175 hospitals in 17 states between Feb. 1-Sept. 15, 2020. Most of the patients were COVID-19 free (4,819 or 96%), but 210 (4%) patients were positive for COVID-19 and of these, 64 (or, 30%) died as compared to 262 of 4,819 (5%) without COVID-19.

Why a COVID-19 diagnosis was more deadly for patients with diabetic ketoacidosis is not known, but researchers suspect the presence of other factors—such as advanced age or a high BMI—may be at play.

“The cause for the considerably higher mortality in the COVID-19–positive population is unknown. Contributing factors could include obesity and a more severe stress state (as suggested by higher insulin requirements). These findings are worrisome and warrant further investigation,” the authors wrote.

Diabetic ketoacidosis occurs as a result of high blood sugar levels and insulin deficiency so treatment usually includes continuous insulin infusions. The condition can be aggravated by ensuing hyperglycemia, dehydration, and acidosis-producing derangements in intermediary metabolism.

In recent years, more people have been hospitalized as a result of diabetic ketoacidosis, however, in-hospital deaths have fallen for this group of patients. Yet, this study shows that a COVID-19 diagnosis for diabetic ketoacidosis reversed that trend.

Pasquel et al. analyzed severity markers of diabetic ketoacidosis, insulin requirements, complications, and in-hospital case fatalities of patients with and without COVID-19.

Patients with COVID-19 were older on average (56 years mean age) as compared to the mean age of 47 years for the study overall. Patients with COVID-19 also had a higher body mass index (31 (P < .001) as compared to the study average of 28 (P < .001). Older patients with COVID-19 (65 years and older) were more likely to have complications from cardiovascular disease and diabetes as compared to patients who were 45 years old or younger (cardiovascular disease: 16 [22%] vs 1 [2%] (P < .001). Diabetes complications occurred in 10 [14%] patients with COVID-19 as compared to 1 [2%] without (P = .02). Metabolic parameters (glucose, hemoglobin A1c, potassium, sodium, bicarbonate, and anion gap) were similar between patients with and without COVID-19. COVID-19 patients were more likely to have acute kidney injury (64 of 210 [30%]) as compared to patients without COVID-19 (498 of 4,819 [10%]).

Regardless of COVID-19 status, mortality was aligned with advanced age. For patients 65 years and older with COVID-19, mortality was 45% (33 of 73 patients) and 13% (110 of 860 patients) for patients without COVID-19.

Pasquel et al. found that a COVID-19 diagnosis was aligned with a higher death rate (19% or 10 of 54 patients) in younger patients (45 years and younger) as compared with 2% (41 of 2,290 patients) of patients without COVID-19.

COVID-19 patients had more insulin requirements and a prolonged duration of continuous insulin infusions in order to resolve diabetic ketoacidosis status. Hypokalemia and hyperosmolality were common in both groups. And, hypoglycemia rates were similar in both groups.

“In this analysis, the mortality observed in patients with COVID-19 was high and increased across age strata, with older adults (>65 years) having a mortality of 45%,” the authors wrote.

Among the limitations noted in this study included the lack of data on admission diagnosis, race, duration of diabetes, additional disease severity markers, or COVID-19–specific therapy, such as the use of corticosteroids.

“Several transformations in diabetes care are occurring during the COVID-19 pandemic to reduce the number of patient interactions. However, it is not known whether fewer interactions may increase mortality by causing a delay in the resolution [of diabetic ketoacidosis.

Disclosures: Dr. Pasquel reported receiving research support from Dexcom and Merck and personal fees from Boehringer Ingelheim, AstraZeneca, Eli Lilly and Co, and Merck outside the submitted work. Some other authors also noted receiving grants from pharmaceutical companies.


Pasquel FJ, Messler J, Booth R, et al. Characteristics of and Mortality Associated With Diabetic Ketoacidosis Among US Patients Hospitalized With or Without COVID-19. JAMA Netw Open. 2021;4(3):e211091. doi:10.1001/jamanetworkopen.2021.1091

– This article originally appeared on Endocrinology Advisor

ECO #01105-A