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December 22, 2020
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Treating hyperglycemia decreases COVID-19 mortality in non-ICU patients

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Severe hyperglycemia after hospital admission for COVID-19 significantly increased mortality odds among individuals not in the ICU, according to a study published in Diabetes Care.

“Patients in the non-ICU setting that did not have their glucose managed early in the hospital stay had a seven times higher risk of death compared to patients who did have their glucose controlled,” Jordan Messler, MD, SFHM, FACP, executive director of clinical practice at Glytec Inc., told Healio. “Patients with COVID-19 with hyperglycemia should promptly receive treatment to improve their glucose in the hospital, like they would receive any other treatment to manage their COVID-19. Glucose control can save lives.”

Messler is the executive director of clinical practice at Glytec Inc.

Messler and colleagues analyzed pool data from Glytec’s national database of 1,544 individuals admitted to 91 hospitals in 12 states for COVID-19 from March 1 to May 8. Of the study population, 360 were admitted to the ICU and 1,184 were not directly admitted to the ICU. Data on HbA1c were analyzed where they were available from hospital records or transferred into hospital records from an outside laboratory.

Participants were broken into four groups as defined by mean glucose level on days 2 and 3 of admission for the non-ICU group and day 2 for those in the ICU cohort. The reference group included individuals with a mean glucose of less than 7.77 mmol/L (139.9 mg/dL). An alternate reference group included participants with a mean glucose from 7.83 mmol/L to 10 mmol/L (140.9 mg/dL to 180 mg/dL). Hyperglycemia was defined as blood glucose of greater than 10 mmol/L, and severe hyperglycemia as a mean glucose of greater than 13.88 mmol/L (249.8 mg/dL).

David C. Klonoff

“Prior studies have shown hyperglycemia on admission to the hospital is a predictor of death and other severe outcomes of COVID-19,” David C. Klonoff, MD, medical director at the Diabetes Research Institute at Mills-Peninsula Medical Center in San Mateo, California, and clinical professor of medicine at UCSF, told Healio. “I believe this is the first study reporting on the impact of achieved glycemia early in hospitalization in ICU and non-ICU settings. This retrospective study asked whether improved glycemia within the first 2 to 3 days of a hospitalization will better predict outcomes than admission glycemia. The mean blood glucose on days 2 and 3 was used as a surrogate metric for the achievement of successful treatment.”

In both the non-ICU and ICU cohorts, 40% had diabetes. The mean blood glucose was higher in the ICU group vs. the non-ICU cohort (10.1 mmol/L vs. 8.9 mmol/L).

In the non-ICU group, the mortality rate was highest among those with severe hyperglycemia at 21%. The mortality rate in the reference group was 15%. Those with severe hyperglycemia 2 to 3 days after admission had the highest mortality risk compared with those in the reference group (HR = 7.6; 95% CI, 1.95-29.6). Admission glucose did not significantly modify the association.

In addition, hypoglycemia increased odds for mortality for those in the non-ICU group (OR = 2.2; 95% CI, 1.35-3.6). Hypoglycemia was associated with a higher likelihood for acute kidney injury (OR = 2.15; 95% CI, 1.33-3.49).

In the ICU cohort, those with severe hyperglycemia also had the highest mortality rate at 45%, whereas those in the reference group had a mortality rate of 29%. Severe hyperglycemia at ICU admission was associated with an increased mortality risk compared with the reference group (HR = 3.14; 95% CI, 1.44-6.88). However, the association was no longer significant on day 2.

“It’s been shown repeatedly that high blood glucose on admission, whether due to diabetes or stress hyperglycemia, is a marker of worse disease,” Messler said. “What’s been less clear is whether controlling the glucose during the hospital stay impacts outcomes. With this important and novel metric of achieved glucose, we identify this early critical period of opportunity to treat. Identify patients with hyperglycemia on admission and don’t delay treatment.”

Klonoff said future research should examine how insulin treatment and other medications influence hyperglycemia.

“I would like to see a prospective study test our findings to determine for hospitalized COVID-19 patients with diabetes the optimal type of insulin management (intravenous vs. subcutaneous), and whether or not specific treatments, such as corticosteroids, hydroxychloroquine, or vasopressors, are associated with improved outcomes,” Klonoff said.

For more information:

David C. Klonoff, MD, can be reached at dklonoff@diabetestechnology.org

Jordan Messler, MD, SFHM, FACP, can be reached at jmessler@glytecsystems.com