key: cord-0732263-4bfhobzp
authors: Singh, Awadhesh Kumar; Singh, Ritu
title: At-admission hyperglycemia is consistently associated with poor prognosis and early intervention can improve outcomes in patients with COVID-19
date: 2020-08-29
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2020.08.034
sha: c6561941be676c555f06068c6c58d159e7446e8d
doc_id: 732263
cord_uid: 4bfhobzp

BACKGROUND & AIMS: At-admission hyperglycemia have been associated with poorer outcome during critical illnesses. At-admission hyperglycemia in previously unknown diabetes is not uncommonly encountered entity in patients with COVID-19. We sought to find out the outcomes of at-admission hyperglycemia and effect of early intervention to achieve optimal glycemic control in relation to COVID-19 patients. METHODS: We searched the PubMed and Google Scholar database up till August 20, 2020 using specific keywords related to our aims and objectives. RESULTS: All currently available evidences clearly hint that at-admission hyperglycemia in patients with COVID-19 is associated with a poorer outcome, compared with normoglycemic individuals. Fortunately, early intervention by achieving an optimal glycemic control has also been associated with a significant improvement in the outcomes in patients with COVID-19. CONCLUSION: At-admission hyperglycemia should be taken seriously by all clinicians treating patients with COVID-19. All efforts should be made towards an optimal glycemic control in patients with COVID-19, even in absence of pre-existing diabetes.

At-admission hyperglycemia observed during acute medical or surgical illnesses has been a medical conundrum for a long time. While some find at-admission hyperglycemia as a provocateur, others believe this entity as an innocent bystander [1] . Whatever may be the argument, at-admission hyperglycemia is attributed toa. Physiological response to the stress hormones (epinephrine or cortisol) released during acute illness that could be directly proportional to the severity of illness, b. Impaired insulin signaling due to metabolic dysregulations associated with the severity of illness. Irrespective of the patho-physiological mechanism, exaggerated inflammatory response induced by stress-hyperglycemia has been linked to endothelial dysfunction, increased oxidative stress as a result of free radial formation, consequently inducing a prothrombotic state leading to cellular and tissue injury in critically-ill patients [2] . Notably, at-admission hyperglycemia has often been linked to a poorer clinical outcome during the critical illnesses [3, 4] , acute coronary syndrome [5, 6] and revascularization procedures [7, 8] .

Intriguingly, stress-induced hyperglycemia encountered at hospital admission in people who had no history of diabetes has been shown to carry a worser prognosis, compared to individuals with diabetes [9] .

Similarly, at-admission hyperglycemia was an independent predictor of poor outcome during the past Severe Acute Respiratory Syndrome Coronavirus infection-1 (SARS-CoV-1) that used angiotensin converting enzymes 2 (ACE2) as a principal entry receptor. It was believed that hyperglycemia induced glycosylation of ACE2 may be associated with an increase in clinical severity with SARS-CoV-1 infection [10]. Since ACE2 is also a principal entry receptor for SARS-CoV-2 infection, it is conceivable that at-admission hyperglycemia may J o u r n a l P r e -p r o o f also be associated with a poor outcome in patients with Coronavirus disease-2019 . Recently, we reviewed the literature on outcomes associated with new-onset hyperglycemia with or without blood glucose in diabetes range in patients with . In this short communication, we sought to review and descriptively analyze the studies that evaluated the outcomes of at-admission hyperglycemia in patients with COVID-19. Additionally, we also evaluated the outcomes associated with early intervention in patients with COVID-19, who presented with at-admission hyperglycemia.

We searched the PubMed and Google Scholar database up till August 20, 2020 using specific keywords that includes "COVID-19", OR "SARS-CoV-2" AND "At-admission hyperglycemia", OR "Clinical severity", OR "Outcomes", OR "Glycemic control". We retrieved full text of all the articles including the cross references related to our topics published in English language.

Nine studies so far have studied the outcomes of at-admission hyperglycemia in patients with or without diabetes and COVID-19. While 2 studies additionally evaluated the outcomes with new-onset hyperglycemia, 2 studies also evaluated the outcomes of early intervention to achieve optimal glycemic control in patients with COVID-19 and higher at-admission hyperglycemia.

Several studies have recently evaluated the outcomes of at-admission hyperglycemia in patients with COVID-19. While in some studies at-admission hyperglycemia was defined when blood glucose measured at the time of hospital 80.0% respectively, p=0.03). Table 1 summarizes the finding from studies done to evaluate the outcomes associated with at-admission hyperglycemia in patients with COVID-19. Additionally, some studies also evaluated the outcomes in patients with new-onset hyperglycemia with or without diabetes, compared with normoglycemic individuals and pre-existing diabetes with COVID-19.

Collectively, this suggest that at-admission hyperglycemia is associated with poor outcomes. Moreover, these findings have immense importance in the context of countries like India given that prevalence of undiagnosed diabetes is very high and being detected for the first time during this pandemic of COVID-19. Furthermore, this underlines the importance of recent call for action for strict glycemic control in patients with COVID-19 by the group of Indian clinicians [21].

In summary, these evidences suggest -a. At-admission hyperglycemia is strongly correlated with poorer outcomes in patients with COVID-19, b. An early intervention to optimally lower the blood glucose might help in improving the outcomes, although we still lack large intervention studies in such patients with COVID-19. Nevertheless, all attempts must be made to achieve an optimal J o u r n a l P r e -p r o o f glycemic control in those having at-admission hyperglycemia, even in the absence of pre-existing diabetes. This is in concordance to a recent call for action for strict glycemic control in patients with COVID-19 by the group of Indian clinicians.

Conflict of interest -None for AKS and RS. 

Hyperglycemia and Adverse Outcomes in Acute Coronary Syndromes: Is Serum Glucose the Provocateur or Innocent Bystander?

Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes

Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis

Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview

New-onset hyperglycemia and acute coronary syndrome: a systematic overview and meta-analysis

Impact of hyperglycemia in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: the HORIZONS-AMI trial

Admission hyperglycemia predicts

Stress hyperglycaemia

FPG-fasting plasma glucose; FBG-fasting blood glucose; OR-odds ratio

NA-not available/applicable; DM-diabetes mellitus; * Group 3A: defined by a HbA1c ≥6.5% or a random glucose level ≥11.1 mmol/L (≥200 mg/dl) with signs and symptoms of hyperglycemia; ^ Group 1: at-admission blood glucose <7.78 mmol/L (<140 mg/dL

1 mmol/L (≥110 mg/dL)

Group 2: Prediabetes/HbA1C of 5.7 -6.4%, Group 3A: persistently elevated FBG >125 mg/dL and requiring insulin therapy; @ at-admission hyperglycemia was defined, if plasma glucose >7

Early and intensive intervention improves the outcome.