Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: A systematic review of literature

Pal, Rimesh; Banerjee, Mainak; Yadav, Urmila; Bhattacharjee, Sukrita

doi:10.1016/j.dsx.2020.08.015

Cited by 102 publications

(117 citation statements)

References 60 publications

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“…Additionally, we demonstrated an independent correlation of mixed DKA/HHS related to COVID-19 infection with non-surviving. Our results are in keeping with the ones reported in the systematic review of Pal et al, who describe a statistically significant difference in arterial blood pH between COVID-19-related DKA survivors (7.23, 95% CI: 7.09-7.26) when compared with non-survivors (7.00, 95% CI: 6.91-7.11); P=0.017 [20]. Despite that data linking increased osmolarity with increased fatality rate in COVID-19 patients are lacking, it is well known that death occurs in 5-16% of patients with HHS in general, a rate that is about 10-fold higher than that reported for DKA [73][74][75].…”

Section: Discussionsupporting

confidence: 92%

Acute Metabolic Emergencies in Diabetes and COVID-19: a systematic review and meta-analysis of case reports

Papadopoulos¹,

Koutroulos²,

Zikoudi³

et al. 2021

Preprint

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BackgroundCOVID-19 is associated with DKA (Diabetic Ketoacidosis), HHS (Hyperglycaemic Hyperosmolar State) and EDKA (Euglycaemic DKA). High mortality has been observed in COVID-19-related diabetic ketoacidosis; however, evidence is scarce.MethodsA systematic literature review was conducted using EMBASE, PubMed/Medline, and Google Scholar from January to December 2020 to identify all case reports describing DKA, HHS, and EDKA, in COVID-19 patients. The Joanna Briggs Institute critical appraisal checklist for case reports was used for quality assessment. Univariate and multivariate analysis assessed correlations of study origin, combined DKA/HHS, age, BMI, HbA1c, administered antidiabetics, comorbidities, symptoms onset, disease status (DS), CRP, ferritin, d-dimers, glucose, osmolarity, pH, bicarbonates, ketones, lactates, β-hydroxybutyric acid, anion gap, and acute kidney injury (AKI) with outcome. The relevant protocol was submitted to PROSPERO database (ID: 229356).ResultsFrom 312 identified publications, 41 including 71 cases analyzed qualitatively and quantitatively. The types of acute metabolic emergencies observed were DKA (45/71, 63.4%), EDKA (6/71, 8.5%), combined DKA/HHS (19/71, 26.8%), and HHS (1/71, 1.4%). Overall mortality was 32.4% (22/68 patients; 3 missing). Multivariate analysis by classical regression demonstrated that COVID-19 DS4 (P=3•10−8), presence of DKA/HHS (P=0.021), and development of AKI (P=0.037) were all independently correlated with death. Increased DS (P=0.003), elevated lactates (P<0.001), augmented anion gap (P<0.001), and presence of AKI (P=0.002) were associated with DKA/HHS. SGLT-2i administration was linked with EDKA (P=0.004); however, a negative association with AKI was noted (P=0.023).ConclusionCOVID-19 intertwines with acute metabolic emergencies in diabetes leading to increased mortality. Key determinants are critical COVID-19 illness, coexistence of DKA/HHS and AKI. Awareness of clinicians to timely assess them might enable early detection and immediate treatment commencing. As previous treatment with was negatively associated with AKI, thus implying a prophylactic effect on renal function, the issue of discontinuation of SGLT-2i in COVID-19 patients remains to be further evaluated.Key messagesWhat is already known on this subject▸Diabetes mellitus (DM) is a risk factor for poor outcomes in COVID-19 patients.▸Diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) are not rare in COVID-19 diabetic and non-diabetic patients; key determinants of outcome remain unknown.What this study adds▸COVID-19 intertwines with acute metabolic emergencies in diabetes leading to increased mortality; key determinants are critical COVID-19 illness, coexistence of DKA and HHS as well as development of acute kidney injury.▸SGLT2-i administration is linked with euglycaemic DKA in patients with COVID-19, though preserving renal function.

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Section: Discussionsupporting

confidence: 92%

Acute Metabolic Emergencies in Diabetes and COVID-19: a systematic review and meta-analysis of case reports

Papadopoulos¹,

Koutroulos²,

Zikoudi³

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Although ketoacidosis is typically a problem closely associated with T1DM, in patients with COVID-19, ketoacidosis can also occur in those with T2DM. For example, in a systematic review, 77% of patients with COVID-19 who developed ketoacidosis had T2DM 28 .…”

Section: Potential Mechanismsmentioning

confidence: 99%

COVID-19 and diabetes mellitus: from pathophysiology to clinical management

et al. 2020

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Initial studies found increased severity of coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with diabetes mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycaemia. Interacting with other risk factors, hyperglycaemia might modulate immune and inflammatory responses, thus predisposing patients to severe COVID-19 and possible lethal outcomes. Angiotensin-converting enzyme 2 (ACE2), which is part of the renin–angiotensin–aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target. Preliminary data, however, do not suggest a notable effect of glucose-lowering DPP4 inhibitors on SARS-CoV-2 susceptibility. Owing to their pharmacological characteristics, sodium–glucose cotransporter 2 (SGLT2) inhibitors might cause adverse effects in patients with COVID-19 and so cannot be recommended. Currently, insulin should be the main approach to the control of acute glycaemia. Most available evidence does not distinguish between the major types of diabetes mellitus and is related to type 2 diabetes mellitus owing to its high prevalence. However, some limited evidence is now available on type 1 diabetes mellitus and COVID-19. Most of these conclusions are preliminary, and further investigation of the optimal management in patients with diabetes mellitus is warranted.

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“…In addition to acidotic pH in inflamed and hypoxic tissues, respiratory and metabolic acidosis is a common complication observed in COVID-19 patients, especially in patients with severe disease ( 37 ). Also, COVID-19 may aggravate ketoacidosis in diabetes patients and cause kidney injuries, leading to metabolic acidosis in patients ( 38 – 40 ). As a proton-sensing GPCR, GPR4 is optimally activated under acidic extracellular pH (6.4–6.9) and partially activated at physiological pH 7.4 ( 41 , 42 ).…”

Section: Evaluation Of the Hypothesismentioning

confidence: 99%

Can GPR4 Be a Potential Therapeutic Target for COVID-19?

et al. 2021

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Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in late 2019 and has since rapidly become a global pandemic. SARS-CoV-2 infection causes damages to the lung and other organs. The clinical manifestations of COVID-19 range widely from asymptomatic infection, mild respiratory illness to severe pneumonia with respiratory failure and death. Autopsy studies demonstrate that diffuse alveolar damage, inflammatory cell infiltration, edema, proteinaceous exudates, and vascular thromboembolism in the lung as well as extrapulmonary injuries in other organs represent key pathological findings. Herein, we hypothesize that GPR4 plays an integral role in COVID-19 pathophysiology and is a potential therapeutic target for the treatment of COVID-19. GPR4 is a pro-inflammatory G protein-coupled receptor (GPCR) highly expressed in vascular endothelial cells and serves as a “gatekeeper” to regulate endothelium-blood cell interaction and leukocyte infiltration. GPR4 also regulates vascular permeability and tissue edema under inflammatory conditions. Therefore, we hypothesize that GPR4 antagonism can potentially be exploited to mitigate the hyper-inflammatory response, vessel hyper-permeability, pulmonary edema, exudate formation, vascular thromboembolism and tissue injury associated with COVID-19.

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Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: A systematic review of literature

Cited by 102 publications

References 60 publications

Acute Metabolic Emergencies in Diabetes and COVID-19: a systematic review and meta-analysis of case reports

Acute Metabolic Emergencies in Diabetes and COVID-19: a systematic review and meta-analysis of case reports

COVID-19 and diabetes mellitus: from pathophysiology to clinical management

Can GPR4 Be a Potential Therapeutic Target for COVID-19?

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