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      COVID-19-associated euglycemic diabetic ketoacidosis in a patient with type 2 diabetes on SGLT2 inhibitor: a case report

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          Abstract

          Type 2 diabetes mellitus (DM) patients are at high risk for the development of severe COVID-19. Euglycemic diabetic ketoacidosis (eu-DKA) is a rare life-threatening complication associated with the use of SGLT2 inhibitor that may be unnoticed, particularly in a pandemic setting, due to the absence of significant hyperglycemia, delaying its treatment. In this report, we describe a case of a 56-year-old patient who presented an elevated anion gap metabolic acidosis during a SARS-CoV-2 infection and was diagnosed with SGLT2-associated euglycemic diabetic ketoacidosis. COVID-19 may increase patients’ insulin demand, present gastrointestinal symptoms, and increase the production of ketone bodies. This situation can be worsened in susceptible diabetic patients on SLGT2 inhibitors, due to the persistent glycosuria, which can cause volume depletion. Recently some authors recommended that insulin-deficient patients or those using SGLT2 inhibitors should monitor for ketosis using available home testing kits in case of infections and should discontinue the medication in case of COVID-19. Given the increased use of this drug class in the management of type 2 DM patients due to its reduction of cardiovascular risk, we set out to emphasize the importance for the medical community to consider the possibility of eu-DKA on SARS-CoV-2-infected patients using SLGT2 inhibitors, so physicians can provide these patients with appropriate therapy promptly.

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          Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes

          Lihua Zhu, Zhi-Gang She, Xu Cheng … (2020)
          Summary Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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            Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis

            Ren Mao, Yun Qiu, Jin-Shen He … (2020)
            Summary Background The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system. Methods In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates. Findings We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2–5; range 0–15; I 2=74%). The pooled prevalence of digestive symptoms was 15% (10–21; range: 2–57; I 2=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9–32; range 1–53; I 2=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of gastrointestinal symptoms (odds ratio [OR] 1·60 [95% CI 1·09–2·36]; p=0·0020; I 2=44%) and liver injury (2·20 [1·60–3·02]; p<0·00001; I 2=36%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4–19; range 3–23; I 2=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22–5·48]; p=0·030; I 2=73%). Patients with gastrointestinal involvement had a higher prevalence of complication (OR 2·51 [95% CI 1·62–3·89]; p<0·0001; I 2=0%). Interpretation Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients. Funding None.
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              Practical recommendations for the management of diabetes in patients with COVID-19

              Stefan R. Bornstein, Francesco Rubino, Kamlesh Khunti … (2020)
              Summary Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20–50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.
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                Author and article information

                Contributors
                Thomaz Alexandre Costa:
                ORCID: http://orcid.org/0000-0003-1789-6694
                thomazacosta@gmail.com
                Journal
                Journal ID (nlm-ta): Diabetol Int
                Journal ID (iso-abbrev): Diabetol Int
                Title: Diabetology international
                Publisher: Springer Singapore (Singapore )
                ISSN (Print): 2190-1678
                ISSN (Electronic): 2190-1686
                Publication date (Electronic): 28 October 2020
                Pages: 1-4
                Affiliations
                [1 ]GRID grid.414358.f, ISNI 0000 0004 0386 8219, Hospital Alemão Oswaldo Cruz, Intensive Care Unit, ; São Paulo, Brazil
                [2 ]GRID grid.8395.7, ISNI 0000 0001 2160 0329, Clinical Pharmacology Unit, Drug Research and Development Center (NPDM), , Federal University of Ceará (UFC), ; Coronel Nunes de Melo #1000, Fortaleza, CE 60430-275 Brazil
                [3 ]GRID grid.11899.38, ISNI 0000 0004 1937 0722, University of Sao Paulo Heart Institute, ; São Paulo, Brazil
                Author information
                http://orcid.org/0000-0003-1789-6694
                Article
                Publisher ID: 473
                DOI: 10.1007/s13340-020-00473-3
                PMC ID: 7592186
                PubMed ID: 33133998
                SO-VID: 8be1116c-c95d-4d9f-81b6-ad8e5ae6fe3f
                Copyright © © The Japan Diabetes Society 2020
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 17 August 2020
                Date accepted : 15 October 2020
                Categories
                Subject: Case Report

                Keywords: coronavirus disease 2019 (covid-19),type 2 diabetes,euglycemic diabetic ketoacidosis,sglt2 inhibitor
                Data availability:
                Keywords: coronavirus disease 2019 (covid-19), type 2 diabetes, euglycemic diabetic ketoacidosis, sglt2 inhibitor

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