Association of acute‐to‐chronic glycemic ratio and outcomes in patients with COVID‐19 and undiagnosed diabetes mellitus: A retrospective nationwide cohort study

Abstract

Aims/Introduction To assess the association of undiagnosed diabetes mellitus and its acute‐to‐chronic glycemic ratio with clinical outcome in patients hospitalized with coronavirus disease 2019 (COVID‐19) using a large‐scale nationwide registry in Japan. Materials and Methods Overall, 4,747 patients were included between July 2021 and January 2022. We evaluated blood glucose and glycated hemoglobin levels at admission, and calculated the acute‐to‐chronic glycemic ratio for each non‐diabetes mellitus, undiagnosed diabetes mellitus and pre‐existing diabetes mellitus group. The primary composite outcome comprised in‐hospital mortality, invasive mechanical ventilation, extracorporeal membrane oxygenation support, intensive care unit admission and transfer to a more advanced medical facility. Results Compared with the non‐diabetes mellitus group, the undiagnosed diabetes mellitus group was significantly associated with a worse COVID‐19 outcome (odds ratio 2.18, 95% confidence interval 1.50–3.18). In patients with undiagnosed diabetes mellitus, the 3rd tertile of the acute‐to‐chronic glycemic ratio was linked with a worse COVID‐19 outcome compared with the 1st tertile (odds ratio 3.33, 95% confidence interval 1.43–7.77), whereas glycated hemoglobin levels were not; among patients with pre‐existing diabetes mellitus, glycated hemoglobin levels were linked with a worse outcome. Conclusions Among patients with undiagnosed diabetes mellitus with COVID‐19, the magnitude of elevation of blood glucose from chronic to acute levels is associated with worse outcomes.

Modification effect of receipt of diabetes care on the association between COVID‐19 infection and HbA1c level during the first year of the coronavirus pandemic using a nationwide population‐based database

“…For example, one study showed that patients with newly diagnosed diabetes who suffered from COVID‐19 were more likely to be admitted to intensive care units than those with previously diagnosed diabetes 6 . Another study reported that those with newly diagnosed diabetes had a higher risk of progression to severe disease than those with pre‐existing diabetes among patients with COVID‐19 9 . However, these studies failed to adjust for pre‐admission glycemic status or to obtain information regarding adherence to diabetes care.…”

“…Next, to analyze the modification effect of adherence to diabetes care on the association between COVID‐19 infection and HbA1c level, we used logistic regression and estimated the risk of an increase in the HbA1c level among individuals undergoing and not undergoing follow‐up for diabetes care in 2019. When we evaluated the modification effect of adherence to diabetes care on the association between HbA1c levels and COVID‐19 infection risk, we applied two methods: one in which HbA1c levels were categorized into HbA1c of 6.5–6.9%, 7.0–7.9%, and ≥8.0% 9 , and the other in which we applied a restricted cubic spline model with 3 knots, treating HbA1c levels as a nonlinear continuous variable with knots placed at 7%, 8%, and 10%. For the assessment of COVID‐19 infection risk, an HbA1c of 6.5–6.9% and 6.5% were set as references in the former and latter models, respectively.…”

“…Among people with diabetes and COVID‐19, individuals with a history of receiving diabetes treatment have a lower risk of severe disease than those without 8 . Untreated diabetes and higher HbA1c levels at admission have both been reported as factors related to a poor prognosis based on a nationwide registry of COVID‐19 in Japan 9 . Thus, untreated diabetes and pre‐admission glycemic control may have been key to the admission of patients with severe COVID‐19.…”

Molecular Mechanisms Responsible for Diabetogenic Effects of COVID-19 Infection—Induction of Autoimmune Dysregulation and Metabolic Disturbances

“…The mechanisms mentioned were proposed by Sathish et al [87] and some other authors [88,89]. Some studies showed that diabetes is related to prolonged hospitalization of patients with COVID-19 [90] and with worse disease outcomes [27,28,79,[91][92][93][94][95][96]. It is also concluded that patients with diabetes mellitus are more prone to developing severe symptoms of COVID-19 [28,93,94,96].…”

“…It is also concluded that patients with diabetes mellitus are more prone to developing severe symptoms of COVID-19 [28,93,94,96]. Moreover, newly diagnosed diabetes during SARS-CoV-2 infection has been linked to an even worse prognosis than pre-existing, probably due to insufficient diabetes regulation [62,92,93,97].…”