Evidence of COVID-19 impacts on glycated hemoglobin levels in a real-world clinical cohort

In a recent study posted to the medRxiv* preprint server, researchers established the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on glycated hemoglobin (HbA1c) levels, type 2 diabetes (T2D) risk, and diabetic ketoacidosis (DKA) through data from the large real-world clinical cohort.

Study: Impacts of COVID-19 on glycemia and risk of diabetic ketoacidosis. Image Credit: joel bubble ben/Shutterstock
Study: Impacts of COVID-19 on glycemia and risk of diabetic ketoacidosis. Image Credit: joel bubble ben/Shutterstock


Pre-existing T2D and high HbA1c levels in patients before SARS-CoV-2 infection are key predictors for the development of coronavirus disease 2019 (COVID-19)-related severity. Moreover, studies have revealed increased hospitalization rates in COVID-19-positive T2D patients, with disease progression attributable to DKA.

Various studies have demonstrated the ability of SARS-CoV-2 to infect adult human pancreatic beta cells in vitro and impair insulin secretions. To date, there is a lack of large controlled clinical studies that could determine the magnitude of glycemic impairment induced by SARS-CoV-2.

To fill this gap, the present study was designed to assess whether COVID-19 increased HbA1c and the risk of developing T2D and DKA.

Study design

In this study, the authors collected data from the COVID-19 data registry developed by the Cleveland clinic that includes records of 81,093 COVID-19-positive patients and a matched control of 1,53,034 COVID-19-negative patients between March 2020 to May 2021.

A retrospective analysis of Electronic Health Records (EHR) was performed to determine the impact of COVID-19 on HbA1c levels. Patients with HbA1c records 12 months before and after the COVID-19 test were selected.

Modified eMERGE algorithm including international classification of diseases (ICD-10) codes determined T2D patients from EHR. Two sub-cohorts of patients with T2D were identified to assess the risk of DKA onset post-COVID-19 infection.

Cox proportional hazards (CoxPH) model measured the association of HbA1c levels with time-to-hospitalization, ventilation, assisted breathing, intensive care unit (ICU) admission, mortality, and T2D onset. Restricted cubic spline CoxPH models estimated non-linear relationships between HbA1C and outcomes of interest.


The findings of the study demonstrated an increase in HbA1c (0.06%) in COVID-19-positive patients, while COVID-19-negative patients showed nil or slight increase in HbA1c (0.02%). Between pre and post-COVID-19 testing, a 0.08% HbA1c increase was observed in COVID-19-positive patients compared to COVID-19-negative patients.

COVID-19-positive patients with and without T2D showed an increase of 0.09% and 0.05% HbA1c levels, respectively, post-infection compared to COVID-19-negative patients.

The authors identified a significant positive association in COVID-19-positive patients between pre-COVID-19 HbA1c level and COVID-19-induced severity factors such as hospitalization time, assisted breathing, and ICU admissions. This association was observed even after restricting the time interval to three months and six months of the pre-COVID-19 HbA1c test.

Higher pre-COVID-19 HbA1c values increased the possibility of diagnosis and risk of the onset of T2D in both COVID-19-positive and COVID-19-negative patients. However, COVID-19-positive patients were more likely to develop T2D post-infection compared to the COVID-19-negative patients. Further, the likelihood of COVID-19-positive patients for T2D diagnosis per unit change in HbA1c was higher compared to the COVID-19-negative patients.

In a cohort of COVID-19-negative and -positive patients with pre-existing T1D, no significant difference was observed in developing risk of DKA. However, COVID-19-positive patients with T2D and on insulin showed 35% and 34% higher risk of DKA, respectively, compared to COVID-19-negative patients with T2D and on insulin.

There was no significant difference in developing DKA in T2D COVID-19-positive and -negative patients who were not on insulin. The authors observed no significant association between hyperosmolar hyperglycemic syndrome (HHS) and COVID-19 infection status of patients with T2D.

COVID-19-positive Black patients with T2D had a 63% higher risk of DKA compared to the COVID-19-negative Black patients with T2D. For White patients with T2D, no difference was observed in DKA risk based on COVID-19 testing results.

The authors observed no significant difference in risk of DKA between males and female COVID-19-positive or -negative T2D patients. COVID-19-positive males with T2D had an increased but statistically insignificant risk of DKA compared to COVID-19-negative patients. However, females with T2D showed a higher risk of DKA if tested COVID-19-positive.


The findings of the study demonstrated a statistically significant but clinically insignificant increase in HbA1c levels post-SARS-CoV-2 infection. Further, the risk of DKA in COVID-19-positive patients was significantly higher in patients with pre-existing T2D who were Black and were on baseline insulin post-COVID-19 infection. This indicated the need for increased awareness for DKA in this patient sub-groups.

COVID-19-positive patients were at greater risk of developing T2D for the same increase in HbA1c in COVID-19-negative patients, which was attributable to enhanced recognition of patients with underlying T2D during COVID-19 management.

The current study overcomes the limitations of previous studies by using a large cohort of COVID-19-positive patients, the measurement of HbA1c levels pre- and post-SARS-CoV-2 infection with respect to T2D, and the inclusion of matched large cohort of COVID-19-negative patients. However, the authors warrant the need for additional research to elucidate the pathogenesis of SARS-CoV-2 infection and DKA in T2D patients.

 *Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Sangeeta Paul

Written by

Sangeeta Paul

Sangeeta Paul is a researcher and medical writer based in Gurugram, India. Her academic background is in Pharmacy; she has a Bachelor’s in Pharmacy, a Master’s in Pharmacy (Pharmacology), and Ph.D. in Pharmacology from Banasthali Vidyapith, Rajasthan, India. She also holds a post-graduate diploma in Drug regulatory affairs from Jamia Hamdard, New Delhi, and a post-graduate diploma in Intellectual Property Rights, IGNOU, India.


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