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Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key Takeaways

  • Results from a retrospective, observational, case-control study of more than 20,000 people from a single US medical center showed a statistically significant but clinically insignificant increase in A1c in people following COVID-19 infection, in both those with and without diabetes.

  • After people received a diagnosis of COVID-19 infection they were 40% more likely to also receive a diagnosis of type 2 diabetes compared with people who tested negative for COVID-19, a difference that was significant and could be explained by the increased medical care received by people who test positive for COVID-19.

  • The risk of incident diabetic ketoacidosis (DKA) among people who tested positive for COVID-19 was significantly higher among those with preexisting type 2 diabetes, those using insulin, and among Black individuals.

Why This Matters

  • The authors said that their study is the first report of evidence that infection with COVID-19 affects A1c levels in a large, real-world clinical cohort.

  • Until now, the impact of COVID-19 infection on A1c remained unclear. Results from previous studies indicated that COVID-19 infection may increase A1c levels, metronidazole et grossesse pdf but the studied cohorts were small and lacked uninfected controls

  • The current study included 8755 people infected with COVID-19, had data from both before and after the infection on diabetes status and A1c levels, and also included many matched, uninfected people who served as controls.

Study Design

  • Data came from a Cleveland Clinic registry that included 81,093 people who tested positive for COVID-19 between March 2020 and May 2021 and 153,034 matched individuals who tested negative for COVID-19 during the same period.

  • The researchers retrospectively selected patients with an A1c recorded within 12 months before their COVID-19 test as well as a second A1c value recorded within 12 months after COVID-19 testing. This produced a study cohort of 8755 COVID-positive people and 11,998 matched people who tested negative for COVID-19.

  • To evaluate the risk of DKA onset after COVID-19 infection, the authors identified two sub-cohorts that excluded those with a history of DKA. The sub-cohorts were 701 people with type 1 diabetes, and 21,830 with type 2 diabetes.

Key Results

  • The investigators found a statistically significant but clinically insignificant A1c increase following a positive COVID-19 test, an average A1c increase of 0.06 percentage points. Those who tested negative for COVID-19 had a clinically insignificant change in their average A1c level that was of borderline statistical significance, an average increase of 0.02 percentage points, P = .05

  • The statistically significant but clinically insignificant increase in A1c following infection with COVID-19 was similar in people with and without type 2 diabetes prior to infection.

  • In patients with type 2 diabetes who became infected with COVID-19, the researchers saw significant positive associations between higher A1c levels before infection and time to hospitalization (hazard ratio, 1.07), need for assisted breathing (HR, 1.06), and ICU admission (HR, 1.07).

  • Following a COVID-19 infection, people were 40% more likely to receive a diagnosis of incident type 2 diabetes compared with matched uninfected people. The authors said a possible explanation is that after diagnosis of COVID-19, infected people in general received more intensified care that led to better identification of those with underlying type 2 diabetes.

  • The 701 people included with preexisting type 1 diabetes showed no significant difference in their rate of developing DKA between those infected and not infected with COVID-19.

  • Among the 21,830 people with preexisting type 2 diabetes, the DKA risk was a significant 35% greater for those who were infected with COVID-19 compared with those who were uninfected. The magnitude of this increased relative risk was even higher among the patients with type 2 diabetes who used insulin as part of their treatment.  

  • The difference in DKA risk didn’t differ between Black and White patients who were not infected with COVID-19, but among those infected by COVID-19, Black patients were more than twice as likely to be diagnosed with DKA compared with White patients, a significant difference.

  • Black patients with type 2 diabetes who became infected with COVID-19 had a significant 63% increased rate of DKA compared with Black patients with type 2 diabetes who remained uninfected.

Limitations

  • The study included patients with A1c measurements made up to 12 months prior to their COVID-19 test, and hence comorbid conditions, medication changes during this period, or other factors may have affected subsequent A1c levels. To address this, the authors also assessed outcomes at 3- and 6-month intervals, which produced results consistent with the 12-month findings.

  • The researchers did not have A1c values for many of the more than 234,000 people in the entire registry who underwent COVID-19 testing from March 2020-May 2021 at the Cleveland Clinic, omissions that may have biased the study cohort.

  • This was a single-center study. Some patients may have received care outside of the center and hence records of those episodes could not be included.

Disclosures

  • The study received no commercial funding.

  • Four authors received consulting and speaker honoraria and research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Diasome, Eli Lilly, Merck, Novo Nordisk, and Sanofi.

  • Three authors have intellectual property related to treatment decision-making in the context of type 2 diabetes.

This is a summary of a preprint research study “Impacts of COVID-19 on glycemia and risk of diabetic ketoacidosis,” written by researchers at the Cleveland Clinic on medRxiv, provided to you by Medscape. The study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.

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