Predictors of new-onset diabetic ketoacidosis in patients with moderate to severe COVID-19 receiving parenteral glucocorticoids: A prospective single-centre study among Indian type 2 diabetes patients – ScienceOpen
Predictors of new-onset diabetic ketoacidosis in patients with moderate to severe COVID-19 receiving parenteral glucocorticoids: A prospective single-centre study among Indian type 2 diabetes patients
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Abstract
Background and aim
COVID-19 infection predisposes to diabetic ketoacidosis(DKA); whether glucocorticoids
enhances this risk is unknown.
We aimed to study the occurrence of DKA after initiating glucocorticoids in patients
with type 2 diabetes mellitus(T2DM) and moderate-to-severe COVID-19, and identify
predictors for it.
Methods
Patients with T2DM and moderate or severe COVID-19 infection were prospectively observed
for development of new-onset DKA for one week following initiation of parenteral dexamethasone.
Clinical and biochemical parameters were compared between those who developed DKA
(Group A) and those who didnot (Group B). Logistic regression was done to identify
independent risk-factors predicting DKA; ROC-curve analysis to determine cut-offs
for the parameters in predicting DKA.
Results
Amongst 302 patients screened, n = 196 were finally included, of whom 13.2% (n = 26,Group
A) developed DKA. Patients in Group A were younger, had lower BMI, increased severity
of COVID-19 infection, higher HbA1c%, CRP, IL-6, D-dimer and procalcitonin at admission
(p
all < 0.02). Further, admission BMI (OR: 0.43, CI: 0.27–0.69), HbA1c % (OR: 1.68, CI:
1.16–2.43) and serum IL-6 (OR: 1.02, CI: 1.01–1.03) emerged as independent predictors
for DKA. Out of these, IL-6 levels had the highest AUROC (0.93, CI: 0.89–0.98) with
a cut-off of 50.95 pg/ml yielding a sensitivity of 88% and specificity of 85.2% in
predicting DKA.
Conclusion
There is significant incidence of new-onset DKA following parenteral glucocorticoids
in T2DM patients with COVID-19, especially in those with BMI <25.56 kg/m
2, HbA1c% >8.35% and IL-6 levels >50.95 pg/ml at admission.
A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
Multiple organ damage in severe acute respiratory syndrome (SARS) patients is common; however, the pathogenesis remains controversial. This study was to determine whether the damage was correlated with expression of the SARS coronavirus receptor, angiotensin converting enzyme 2 (ACE2), in different organs, especially in the endocrine tissues of the pancreas, and to elucidate the pathogenesis of glucose intolerance in SARS patients. The effect of clinical variables on survival was estimated in 135 SARS patients who died, 385 hospitalized SARS patients who survived, and 19 patients with non-SARS pneumonia. A total of 39 SARS patients who had no previous diabetes and received no steroid treatment were compared to 39 matched healthy siblings during a 3-year follow-up period. The pattern of SARS coronavirus receptor-ACE2 proteins in different human organs was also studied. Significant elevations in oxygen saturation, serum creatinine, lactate dehydrogenase, creatine kinase MB isoenzyme, and fasting plasma glucose (FPG), but not in alanine transaminase were predictors for death. Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes. Twenty of the 39 followed-up patients were diabetic during hospitalization. After 3 years, only two of these patients had diabetes. Compared with their non-SARS siblings, these patients exhibited no significant differences in FPG, postprandial glucose (PPG), and insulin levels. The organ involvements of SARS correlated with organ expression of ACE2. The localization of ACE2 expression in the endocrine part of the pancreas suggests that SARS coronavirus enters islets using ACE2 as its receptor and damages islets causing acute diabetes.
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