Article

Protracted ketonaemia in hyperglycaemic emergencies in COVID-19: a retrospective case series

July 2020
The Lancet Diabetes & Endocrinology 8(8)

DOI:10.1016/S2213-8587(20)30221-7

Authors:

Eleni Armeni

National and Kapodistrian University of Athens

Sulmaaz Qamar

University College London Hospitals NHS Foundation Trust

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New onset diabetes mellitus in post-COVID-19 patients

Article

Full-text available

Oct 2022

Background: Diabetes, is known to have a bilateral relationship with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Precise mechanism of diabetes onset in COVID-19 patients remains unclear. Aim: To analyse the incidence of new onset diabetes (NODM) among COVID-19 patients, as well as the effect of body mass index (BMI), family history, and steroid use on the incidence of the disease. Methods: Adult, not known diabetic patients, tested positive with Rapid Antigen Test or RT-PCR admitted to a tertiary care hospital and research institute were included in the present prospective observational study. The patients who developed NODM and NOPD (New Onset Pre-diabetes) during the three months follow-up and the risk factors associated were assessed. Patients with HbA1c >6.4% were diagnosed with NODM. An HbA1c of 5.7% to 6.4% was used to characterize NOPD. Results: Out of 273 previously not known diabetic COVID-19 infected individuals, a total of 100 were studied for three months after consent. Mean age of the patients 48.31 ± 19.07 years with male predominance (67%). Among these, 58% were non-diabetics and 42% were pre-diabetics. 6 (10.3%) of the 58 non-diabetics developed NOPD, and 8 (13.8%) developed NODM. 6 (14.2%) of the 42 pre-diabetics became non-diabetic, and 16.6% (7) developed NODM. Family history of DM (P < 0.001), severity at admission (P < 0.006), diabetic ketoacidosis (P < 0.0275), and persistent symptoms were associated significantly with NODM. Those with NODM had significantly greater BMI, O2 duration, steroid duration, FBS, and PPBS (P < 0.001 for all). Nearly 67% of the patients who developed NOPD had shortness of breath as the common symptom at time of admission (P = 0.0165). Conclusion: The incidence of NODM was strongly influenced by positive family history of DM, higher BMI, steroid dosage, and its duration. Hence, patients with COVID-19 need to be under surveillance for blood glucose screening.

An insight to the diabetic ketoacidosis and lactic acidosis among the SARS-COV2 infected individuals

Article

Full-text available

Jun 2022

A huge number of studies have demonstrated the significance correlation between diabetic ketoacidosis as well as other type of ketosis/hyperosmolar metabolic state deterioration conditions and the SARS-COV2 infection. It is investigated in various infected age group, geneders, and countries. It is reported to be correlated to the two types of diabetes (type I DM and type II DM) available as pre-existing co-morbidity, infection related new-onset developed diabetes of both types or even due to hyperinflammation related acute pancreatitis. In fact, although most of the studies have reported greater survival, however, small single center retrospective studies have reported the association of diabetic ketoacidosis with elevated mortality rate that approaches 50%. Mechanistically, the DKA caused metabolic state deterioration due to the glucose metabolism fluctuation is attributed to the bidirectional sophisticated SARS-COV2 infection and different reasons hyperglycemia disease-disease interaction. Nevertheless, exaggerated inflammatory/immune response may also worsen the glycemic state that brings about ketosis. Remarakably, DKA can be developed even in cases of approximately normoglycemic conditions of the SARS-COV2 infection which is fewly reported, yet, it is attributed to SGLT2 inhibitors therapy. The SARS-COV2 infection related DKA complication among diabetic individuals have been treated with the same therapeutic protocol of non-infectious conditions including insulin and IV replenishment therapy however, with significantly greater dosing regimen. It is worthy to note that the infused replenishment fluids should be carefully calculated along with monitoring the lung function besides careful monitoring the potassium and some other electrolytes level particularly while insulin is intravenously infused. Thus, in order to explore the significance of correlation of this metabolic complication with the virus infection poor prognosis as well as higher mortality rate this survey reports the development of DKA as well as the ketosis related metabolic abnormailities while the course of SARS-COV2 infection among individuals with pre-exisitng and new onset diabetes.

Hyperglycemic Crises in Patients with Covid-10

Article

Full-text available

Sep 2020

Nasser Mikhail

Background: It is unclear whether the 2 hyperglycemic crises, diabetic ketoacidosis (DKA), and hyperosmolar hyperglycemic state (HHS) have different characteristics in patients with COVID-19. Objective: to describe prevalence, outcomes, and management of hyperglycemic crisis specifically in patients with COVID-19. Methods: English literature search of electronic databases supplemented by manual search up to July 31st, 2020. Search terms included hyperglycemic crises, diabetic ketoacidosis, COVID-19, ARDS, dexamethasone, mortality, safety. Since no randomized trials are available, all pertinent observational studies, case reports and major organization guidelines were reviewed. Results: DKA occurs in 0.45 to 3.4% of patients with COVID-19 admitted to the hospital, and results in approximately 50% mortality rate. Excessive intravenous hydration should be avoided in patients at risk or having acute respiratory distress syndrome (ARDS) to avoid volume overload. In patients presenting with hyperglycemic crisis and COVID-19 requiring oxygen or on mechanical ventilation, dexamethasone may be given after resolution of hyperglycemic crisis. Insulin doses need to be increased by 50-100% to control dexamethasone-induced hyperglycemia. Selected patients with non-complicated both DKA and COVID-19 may be safely managed by subcutaneous rapid-acting insulin in a step-down unit with blood glucose monitoring every 2 hours. This strategy may spare beds in the intensive care unit (ICU) and personal protective equipment (PPE), and decrease nursing time at bedside. Conclusions: Hyperglycemic crises with COVID-19 are uncommon but carry high mortality rate. Uncomplicated cases may be managed ia step-down unit. Dexamethasone can be given after resolution of hyperglycemic crisis.

COMBINED HYPERGLYCEMIC EMERGENCIES (DKA AND HHS) WITH COVID-19 AT ADMISSION AT A COVID CARE CENTER-CASE SERIES

Article

Full-text available

Jun 2021

Diabetes as comorbidity is associated with increased mortality in patients with SARS CoV-2 infection. We report a case series of 05 cases of combined hyperglycemic emergencies (diabetic ketoacidosis (DKA) plus hyperosmolar hyperglycemic state (HHS) ) from the COVID-19 care center observed for 02 months. The Mean Charlson comorbidity index was 3.2, mean APACHE score at presentation was 13.4, and mean SOFA at presentation was 5.2. All had ARDS with fatal outcomes was seen in 03 out of 05 cases. Serial rising titers of D-dimer and IL-6 were associated with a higher incidence of mortality. In this case series, we observed that the diabetic patients are at risk of developing uncontrolled Hyperglycemia associated with COVID-19 and difcult to manage hyperglycemic emergencies. The associated increase in inammatory markers, e.g D- Dimer, IL-6 are linked to insulin resistance with poor glycemic control and outcome.

Clinical Characteristics of DKA in Patients with COVID-19 Infection: A Case Series

Article

Full-text available

Oct 2021

Backgrounds: Diabetes mellitus (DM) is one of the co-morbidities that can increase the mortality rate of COVID-19 patients. The characteristics of patients who present with diabetic ketoacidosis (DKA) and COVID-19 co-morbidity have not been reviewed sufficiently. Objectives: To investigate the characteristics and outcome of DKA in patients with COVID19 infection. Methods: In this study, we describe 7 patients admitted to our department with impressions of DKA and concomitant COVID-19. Patients' lab data, imaging and outcomes were documented in full detail. Results: The Average of initial random blood sugar and serum HCO3 was 463.71mg/dl and 9.47mmol/L, respectively, among the patients in this survey. The majority of the patients (71%) were presented with DKA symptoms rather than respiratory symptoms related to COVID-19. Four patients expired in this survey. Of the four patients who were expired, all of them presented with moderate DKA, one of them had mild lung involvement, one moderate and two were in a severe category. The average of C-reactive protein (CRP) and Lactate dehydrogenase (LDH) were >150 mg/dl and 813 U/L in the patients who expired respectively. Conclusion: DKA is a common presentation following an infectious etiology in COVID-19 co morbidity. It can presented with atypical symptoms and divergent outcomes. we suggest that more advances studies with a larger sample size is needed to investigate detailed DKA Case Report Boogar et al.; AJMCR, 3(1): 45-56, 2021; Article no.AJMCR.572 46 characteristics, management and outcomes to revise the management protocol of DKA in COVID-19 infection.

Temporal trends in emergency admissions for diabetic ketoacidosis in people with diabetes in England before and during the COVID-19 pandemic: a population-based study

Article

Sep 2021

Background: Diabetic ketoacidosis (DKA) has been reported to be increasing in frequency during the COVID-19 pandemic. We aimed to examine the rates of DKA hospital admissions and the patient demographics associated with DKA during the pandemic compared with in prepandemic years. Methods: Using a comprehensive, multiethnic, national dataset, the Secondary Uses Service repository, we extracted all emergency hospital admissions in England coded with DKA from March 1 to June 30, 2020 (first wave of the pandemic), July 1 to Oct 31, 2020 (post-first wave), and Nov 1, 2020, to Feb 28, 2021 (second wave), and compared these with DKA admissions in the equivalent periods in 2017-20. We also examined baseline characteristics, mortality, and trends in patients who were admitted with DKA. Findings: There were 8553 admissions coded with DKA during the first wave, 8729 during the post-first wave, and 10 235 during the second wave. Compared with preceding years, DKA admissions were 6% (95% CI 4-9; p<0·0001) higher in the first wave of the pandemic (from n=8048), 6% (3-8; p<0·0001) higher in the post-first wave (from n=8260), and 7% (4-9; p<0·0001) higher in the second wave (from n=9610). In the first wave, DKA admissions reduced by 19% (95% CI 16-21) in those with pre-existing type 1 diabetes (from n=4965 to n=4041), increased by 41% (35-47) in those with pre-existing type 2 diabetes (from n=2010 to n=2831), and increased by 57% (48-66) in those with newly diagnosed diabetes (from n=1072 to n=1681). Compared with prepandemic, type 2 diabetes DKA admissions were similarly common in older individuals and men but were higher in those of non-White ethnicities during the first wave. The increase in newly diagnosed DKA admissions occurred across all age groups and these were significantly increased in men and people of non-White ethnicities. In the post-first wave, DKA admissions did not return to the baseline level of previous years; DKA admissions were 14% (11-17) lower in patients with type 1 diabetes (from n=5208 prepandemic to n=4491), 30% (24-36) higher in patients with type 2 diabetes (from n=2011 to n=2613), and 56% (47-66) higher in patients with newly diagnosed diabetes (from n=1041 to n=1625). During the second wave, DKA admissions were 25% (22-27) lower in patients with type 1 diabetes (from n=5769 prepandemic to n=4337), 50% (44-56) higher in patients with type 2 diabetes (from n=2608 to n=3912), and 61% (52-70) higher in patients with newly diagnosed diabetes (from n=1234 to n=1986). Interpretation: Our results provide evidence for differences in the numbers and characteristics of people presenting with DKA during the COVID-19 pandemic compared with in the preceding 3 years. Greater awareness of risk factors for DKA in type 2 diabetes and vigilance for newly diagnosed diabetes presenting with DKA during the COVID-19 pandemic might help mitigate the increased impact of DKA. Funding: None.

Hyperglycemic Crises in Patients with COVID-19

Article

Jan 2020

Clinical Features and Changes in Insulin Requirements in People with Type 2 Diabetes Requiring Insulin When Hospitalised with SARS-CoV-2 Infection

Article

Full-text available

Feb 2022

Background: Uncontrolled hyperglycaemia before and during hospitalisation is a risk factor for adverse outcomes in people with diabetes and SARS-CoV-2 infection. Insulin often at high doses is frequently required to manage hyperglycaemia associated with SARS-CoV-2 infection during hospitalisation. However, there is limited information on the clinical features and sequelae of people with type 2 diabetes (T2DM) not previously on insulin that require insulin as a new treatment when hospitalised with SARS-CoV-2 infection. Aims: To describe the clinical features and insulin treatment sequelae of 113 people with T2DM that required insulin as a new treatment when hospitalised with SARS-CoV-2 infection. Methods: A single-centre study of 113 people with T2DM who were not on insulin before their admission for SARS-CoV-2 infection. The primary aim of our study was to identify clinical and biochemical features that were associated with the need for insulin as a new treatment in people with known T2DM not on insulin treatment at the time of hospitalisation for SARS-CoV-2 infection. We also describe changes in insulin requirements at time of discharge from hospital and 6 weeks later during the first wave of SARS-CoV-2 infection (April-March 2020) in the UK. Clinical, biochemical, and anthropometric data were collected from electronic health records. Results: We observed that of 113 people with T2DM, 35% (n = 39) needed insulin as a new treatment during their hospitalisation for SARS-CoV-2 infection. People requiring insulin were younger, had a higher preadmission HbA1c, were more frequently on oral medication for diabetes before the admission, and were more likely to be obese (body mass index ≥30 kg/m2), with p ≤ 0.001 for all. In multivariable logistic regression analyses, we observed that younger age and higher HbA1c before admission were independently associated with needing insulin, with one-year increase in age associated with decreased odds of needing insulin initiation (OR 0.91, 95% CI 0.83-0.99), and increasing preadmission HbA1c by 1 mmol/mol associated with an increased odds of insulin initiation (OR 1.05, 95% CI 1.002-1.11) (p < 0.05 for both). Of the 39 people with T2DM who required insulin as a new treatment, 28% remained on insulin at the time of discharge with their insulin dose falling from 1.26 U/kg within the first 7 days of admission to 0.39 U/kg at discharge. At 6 weeks after discharge, 24% of people remained on insulin. Conclusion: More than one-third of people with T2DM not previously treated with insulin required new insulin treatment when hospitalised with SARS-CoV-2 infection, and of this group, 24% remained on insulin at 6 weeks after discharge. This study highlights the important variations of insulin requirements in people with T2DM new to insulin and the importance of a dedicated team for patient education and close follow-up.

COVID-19, Hyperglycemia, and New-Onset Diabetes

Article

Oct 2021
DIABETES CARE

Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 (COVID-19) and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have recently reported new-onset diabetes associated with COVID-19. The phenomenon of new-onset diabetes following admission to the hospital has been observed previously with other viral infections and acute illnesses. The precise mechanisms for new-onset diabetes in people with COVID-19 are not known, but it is likely that a number of complex interrelated processes are involved, including previously undiagnosed diabetes, stress hyperglycemia, steroid-induced hyperglycemia, and direct or indirect effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the β-cell. There is an urgent need for research to help guide management pathways for these patients. In view of increased mortality in people with new-onset diabetes, hospital protocols should include efforts to recognize and manage acute hyperglycemia, including diabetic ketoacidosis, in people admitted to the hospital. Whether new-onset diabetes is likely to remain permanent is not known, as the long-term follow-up of these patients is limited. Prospective studies of metabolism in the setting of postacute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities.

Impact of SARS-CoV-2 on Progression of Glycemic and Cardiometabolic Variables and Changes in Insulin Indices: A Longitudinal Study

Article

Full-text available

Oct 2021

Introduction: We aimed to evaluate whether SARS-CoV-2 infection is associated with beta cell dysfunction and progression of glycemic and cardiometabolic variables in an established cohort. Methods: Study participants (n = 352, 46.9% men) underwent a detailed evaluation at two time points: (a) pre-COVID (2016–19) and (b) peri-COVID (2020–21). At the second visit, SARS-CoV-2 infection was determined on the basis of a quantitative S1/S2 IgG antibody test (DiaSorin Liaison) and/or a documented history of infection. Results: A total of 159 (45.2%) participants were seropositive for SARS-CoV-2, of whom 122 (76.7%) had mild/asymptomatic infection. Progression in body mass index (BMI) category [34 (21.4%) vs. 22 (11.4%), p = 0.011] was seen in a significantly higher proportion of the participants in the infected group compared to the non-infected group. Progression in glycemic and insulin indices [homeostasis model assessment of insulin resistance (HOMA-IR), Matsuda index, and oral disposition index (oDI)] categories was also evident in a larger proportion of participants in the infected group; however, the difference was not statistically significant. On logistic regression analysis, the association between SARS-CoV-2 infection and BMI category progression was statistically significant [fully adjusted OR 2.14 (95% CI, 1.18–3.90; p = 0.013)]. Conclusion: In this longitudinal study, predominant mild/asymptomatic SARS-CoV-2 infection was associated with increase in BMI, but not with worsening of beta cell function and insulin resistance, nor glycemic progression.

Impact of COVID-19 on the Endocrine System – a mini-review

Article

Full-text available

Sep 2021

The Corona Virus Disease 2019 (COVID-19) pandemic continues to exert a significant impact on global healthcare systems, causing devastating mortality and morbidity. As time passes and our understanding of this novel respiratory virus deepens, it is increasingly clear that its effects extend beyond that of the respiratory system. The coronavirus responsible for COVID-19, SARS-CoV-2, obtains cellular access through the angiotensin converting enzyme 2 (ACE2) receptor in a process requiring the transmembrane serine protease 2 (TMPRSS2) protein. Both ACE2 and TMPRSS2 are widely expressed in many endocrine glands. This, along with several case reports of thyroid and pituitary disruption in patients with COVID-19, has resulted in significant interest in its impact on the endocrine system. Indeed, as mortality is abated by the increasing availability of effective vaccines, there is increasing focus on the long-term effects on health in COVID-19 survivors. This review summarises data investigating the effects of COVID-19 on each of the endocrine axes to guide appropriate investigations and optimal management.

Ketogenesis promotes tolerance to Pseudomonas aeruginosa pulmonary infection

Article

Oct 2023
CELL METAB

Ying-Tsun Chen

Pseudomonas aeruginosa is a common cause of pulmonary infection. As a Gram-negative pathogen, it can initiate a brisk and highly destructive inflammatory response; however, most hosts become tolerant to the bacterial burden, developing chronic infection. Using a murine model of pneumonia, we demonstrate that this shift from inflammation to disease tolerance is promoted by ketogenesis. In response to pulmonary infection, ketone bodies are generated in the liver and circulate to the lungs where they impose selection for P. aeruginosa strains unable to display surface lipopolysaccharide (LPS). Such keto-adapted LPS strains fail to activate glycolysis and tissue-damaging cytokines and, instead, facilitate mitochondrial catabolism of fats and oxidative phosphorylation (OXPHOS), which maintains airway homeostasis. Within the lung, P. aeruginosa exploits the host immunometabolite itaconate to further stimulate ketogenesis. This environment enables host-P. aeruginosa coexistence, supporting both pathoadaptive changes in the bacteria and the maintenance of respiratory integrity via OXPHOS.

COVID-19: From Emergence to Endemicity - A Comprehensive Review

Preprint

Full-text available

Jul 2023

Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), later renamed Coronavirus Disease 2019 (COVID-19) was first identified in Wuhan, China, in early December 2019. Initially, the China office of the World Health Organization was informed of numerous cases of pneumonia of unidentified etiology in Wuhan, Hubei Province on December 31, 2019. This would subsequently result in a global pandemic with over 76 million confirmed cases of COVID-19 and 6.9 million deaths reported to the WHO. We have analyzed most of the data published since the beginning of the pandemic to compile this comprehensive review of SARS-CoV-2. We look at the core ideas, such as the etiology, epidemiology, pathogenesis, clinical symptoms, diagnostics, histopathologic findings, consequences, therapies, and vaccines. We have also included the long-term effects and myths associated with some therapeutics of COVID-19. This study comprehensively assesses of the SARS-CoV-2 virology, vaccines, medicines, and significant variants identified during the pandemic. Our review article is intended to provide medical practitioners with a better understanding of the fundamental sciences, clinical treatment, and prevention of COVID-19. As of June 2023, this paper contains the most recent data made accessible.

Article

Full-text available

Mar 2023

Background and aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exacerbate hyperglycemia and can cause life-threatening diabetic ketoacidosis (DKA) in patients with diabetes mellitus (DM). The objective of this study is to compare the characteristics of diabetic COVID-19 patients with and without DKA and to determine the predictors of mortality in the setting of COVID-19 and DKA. Methods This is a retrospective single-center cohort study including patients admitted to our hospital with COVID-19 and DM from March 2020 to June 2020. Patients with DKA were filtered as per the diagnostic criteria set by the American Diabetes Association (ADA). Patients with hyperosmolar hyperglycemic state (HHS) were excluded. A retrospective analysis was performed, which included those who developed DKA and those with neither DKA nor HHS. The primary outcome measurement was mortality rate and predictors of mortality for DKA. Results Out of 301 patients with COVID-19 and DM, 30 (10%) had DKA and five (1.7%) had HHS. Mortality was significantly higher in the DKA group compared to the non-DKA/HHS group (36.6% vs 19.5%; OR: 2.38; p=0.03). After adjusting for parameters used for multivariate logistic model for mortality, DKA was no longer associated with mortality (OR: 2.08, p=0.35). The independent predictors for mortality were age, platelet count, serum creatinine, C-reactive protein, hypoxic respiratory failure, need for intubation, and need for vasopressors. Conclusion Our study demonstrates higher mortality rate in diabetic COVID-19 patients with DKA. Though direct and independent statistical association of mortality with DKA could not be proven in our multivariate logistic model, physicians must be vigilant in risk-stratifying and managing these patients in a timely manner.

Clinical profile and outcome of critically ill.14

Article

Full-text available

Mar 2023

Usha Shenoy

Clinical profile and outcome of critically ill COVID-19 patients with diabetic ketoacidosis: A single-centre cross-sectional study in South India

Article

Full-text available

Mar 2023

Sequelae of long COVID, known and unknown: A review of updated information

Article

Mar 2023

Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.

Insulin Requirements for Patients With COVID-19 Presenting With Diabetic Ketoacidosis

Article

Full-text available

Jan 2023

Introduction Recent literature has shown that patients with COVID-19 and diabetic ketoacidosis may require more aggressive treatment than those with diabetic ketoacidosis alone. The primary objective of this study was to assess if intravenous regular human insulin infusion requirements in patients with diabetic ketoacidosis differed between patients with or without COVID-19. Methods This retrospective cohort study evaluated patients with diabetic ketoacidosis who received intravenous regular human insulin infusion during the COVID-19 pandemic. The primary outcome was the amount of intravenous regular human insulin infusion requirements needed during the diabetic ketoacidosis episode. Results Of the 77 patients that met inclusion criteria, 35 were positive for COVID-19 and 42 were negative. The primary outcome of total intravenous regular human insulin infusion requirements needed during the diabetic ketoacidosis episode was not statistically significant and resulted in 1.79±0.61 units/kg/day in the COVID-19 positive group and 1.81±0.6 units/kg/day in the negative group (p=1). Secondary outcomes that were statistically significant between groups were the amount of fluids received in the first 24 hours, potassium supplementation, phosphate supplementation, acute kidney injury, and hypokalemia. Conclusion There was no difference in intravenous regular human insulin infusion requirements in the setting of diabetic ketoacidosis (DKA) between COVID-19 positive and negative patients.

Pediatric endocrinopathies related to COVID-19: an update

Article

Dec 2022

Background: Coronavirus disease 2019 (COVID-19) is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the seventh coronavirus to be linked to human disease. The SARS-CoV-2 virus may have several pathophysiologic interactions with endocrine systems, resulting in disruptions in glucose metabolism, hypothalamus and pituitary function, adrenal function, and mineral metabolism. An increasing amount of evidence demonstrates both the influence of underlying endocrine abnormalities on the outcome of COVID-19 and the effect of the SARS-CoV-2 virus on endocrine systems. However, a systematic examination of the link to pediatric endocrine diseases has been missing. Data sources: The purpose of this review is to discuss the impact of SARS-CoV-2 infection on endocrine systems and to summarize the available knowledge on COVID-19 consequences in children with underlying endocrine abnormalities. For this purpose, a literature search was conducted in EMBASE, and data that were discussed about the effects of COVID-19 on endocrine systems were used in the current study. Results: Treatment suggestions were provided for endocrinopathies associated with SARS-CoV-2 infection. Conclusions: With the global outbreak of COVID-19, it is critical for pediatric endocrinologists to understand how SARS-CoV-2 interacts with the endocrine system and the therapeutic concerns for children with underlying problems who develop COVID-19. While children and adults share certain risk factors for SARS-CoV-2 infection sequelae, it is becoming obvious that pediatric responses are different and that adult study results cannot be generalized. While pediatric research gives some insight, it also shows the need for more study in this area.

COVID-19 and Incident Type 1 Diabetes: Deciphering the Associations

Article

Nov 2022
DIABETES

Implications of a HbA1c based diabetes screening on prevalence and impact of dysglycemia in patients with COVID-19

Article

Oct 2022
J CLIN ENDOCR METAB

Purpose: In patients with SARS-CoV-2 infection, diabetes is associated with poor COVID-19 prognosis. However, case detection strategy is divergent and reported prevalence varies from 5 to 35%. We examined in how far the choice of screening tools impacts the detection rate of dysglycemia and in consequence the estimation of diagnosis-associated risk for moderate (mo) or severe (s) COVID-19. Methods: Non-ICU in-patients with COVID-19 were screened systematically at admission for diabetes (D) and prediabetes (PreD) by HbA1c (A), random blood glucose (B) and known history (C) during 01/NOV/2020-08/MAR/2021. Dysglycemia rate and impact on COVID-19 outcome were analyzed in two screening strategies (ABC vs. BC). Results: 578/601 (96.2%) of admitted patients were screened and analyzed. In ABC, prevalence of D and PreD was 38.2 and 37.5%, respectively. D was significantly associated with an increased risk for more severe COVID-19 (aOR(moCOVID-19): 2.27, 95%CI: 1.16-4.46 and aOR(sCOVID-19): 3.26, 95%CI:1.56-6.38). Patients with PreD also presented more often with more severe COVID-19 than those with normoglycemia (aOR(moCOVID-19): 1.76, 95%CI: 1.04-2.97 and aOR(sCOVID-19): 2.41, 95%CI: 1.37-4.23). Screening with BC only failed to identify 96% of PreD (206/217) and 26.2% of D diagnosis (58/221) and missed association of dysglycemia and COVID-19 severity. Conclusions: Pandemic conditions may hamper dysglycemia detection rate and in consequence the awareness of individual patient risk for COVID-19 severity. A systematic diabetes screening including HbA1c reduces underdiagnosis of previously unknown or new onset dysglycemia, enhances the quality of risk estimation and access of patients at risk to a diabetes-specific intervention.

IMPACT OF ANTIDIABETIC DRUGS ON RISK AND OUTCOME OF COVID-19 INFECTION: A REVIEW

Article

Full-text available

Jun 2022

Based on many reports, an unmistakable link probably exists between diabetes mellitus and COVID-19. A major predisposing factor determining severity and mortality of COVID-19 is diabetes mellitus, diabetic patients were shown to be at higher risk for developing severe COVID-19 disease than non-diabetics; many recent studies reported a striking prevalence of DM in those diagnosed with COVID-19. Accordingly, antidiabetic drugs can possibly impact the clinical course and / or the outcome of this infection, either by alleviating diabetes-associated symptoms, minimizing its complications, or by mitigating or aggravating COVID-19 disease by effects independent from their direct antidiabetic effects. Several antidiabetic drug classes were shown to have varying effects, like blocking viral entry to cells, as well as having immunomodulatory, anti-inflammatory, antifibrotic, or cardioprotective effects; such effects could prove beneficial for COVID-19 patients. On the other hand, some antidiabetic agents may have adverse effects that aggravate patients’ condition like hypoglycemia, fluid retention, increased weight or lactic acidosis, which require special consideration in patient management. Some of the drugs were found in observational studies to either reduce mortality from COVID-19 or pose no harm, but more solid evidence from clinical trials is still lacking.

Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection

Article

Full-text available

Aug 2022

Introduction: Stress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19. Methods: In a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission. Results: Patients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078–6.012) and death (OR 2.281; CI 1.049–7.369) independently of diabetes and other major confounders. Conclusions: In patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.

Clinical Significance of COVID-19 and Diabetes: In the Pandemic Situation of SARS-CoV-2 Variants including Omicron (B.1.1.529)

Article

Full-text available

Mar 2022

The coronavirus disease 2019 (COVID-19) global pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains uncontrolled, with the spread of emerging variants. According to accumulating evidence, diabetes is one of the leading risk factors for a severe COVID-19 clinical course, depending on the glycemic state before admission and during COVID-19 hospitalization. Multiple factors are thought to be responsible, including an altered immune response, coexisting comorbidity, and disruption of the renin-angiotensin system through the virus–host interaction. However, the precise underlying mechanisms remain under investigation. Alternatively, the focus is currently on the diabetogenic and ketosis-prone potential of SARS-CoV-2 itself, even for probable triggers of stress and steroid-induced hyperglycemia in COVID-19. In this article, we present a comprehensive review of the recent literature on the clinical and experimental findings associated with diabetes and COVID-19, and we discuss their bidirectional relationship, i.e., the risk for an adverse prognosis and the deleterious effects on glycometabolism. Accurate assessments of the incidence of new-onset diabetes induced by COVID-19 and its pathogenicity are still unknown, especially in the context of the circulation of SARS-CoV-2 variants, such as Omicron (B.1.1.529), which is a major challenge for the future.

IMPACT OF ANTIDIABETIC DRUGS ON RISK AND OUTCOME OF COVID-19 INFECTION: A REVIEW

Preprint

Full-text available

Feb 2022

Covid-19: A new cause of “provoked” A-β+ Ketosis-Prone Diabetes

Article

Feb 2022
J DIABETES COMPLICAT

Euglycemic diabetic ketoacidosis and COVID ‐19: A combination to foresee in pregnancy

Article

Full-text available

Nov 2021

Diabetic emergencies presenting during the COVID‐19 pandemic: A retrospective case analysis

Article

Full-text available

Oct 2021

Introduction COVID-19 has triggered a global pandemic and is an emerging situation. Diabetes has been associated with significant mortality in SARS and MERS-COV infections. Patients with diabetes are at risk of COVID-19 triggering diabetic emergencies due to known and unknown mechanisms. There is little evidence overviewing the clinical course of COVID-19 patients who either present or have diabetic emergencies during their disease course. Methods We conducted a retrospective case analysis of all patients admitted to our hospital during the COVID-19 pandemic. The inclusion criteria were all patients receiving treatment for COVID-19 and either presenting with a diabetic emergency on admission or developing an emergency during their admission. Data collected for the study were all routinely collected data as part of the admission. We compared these data to nine patients with no COVID-19. Results Thirty patients received treatment for a diabetic emergency, of which 21 also received treatment for COVID-19. Significant differences were found between pH and bicarbonate on admission between RT-PCR-positive and both RT-PCR-negative and non-COVID-19 patients. Other results approaching significance include ALP and eGFR. Discussion Patients suffering from COVID-19 and diabetes concurrently can suffer from profound metabolic disturbance, with a significant difference in inpatient mortality. However further, prospective detailed investigation into biochemical processes is needed to fully elucidate underlying mechanisms that affect these patients' outcomes.

Diabetic ketoacidosis in patients with SARS-CoV-2: a systematic review and meta-analysis

Article

Full-text available

Oct 2021

Abstract Background One possible reason for increased mortality due to SARS-CoV-2 in patients with diabetes is from the complication of diabetic ketoacidosis (DKA). Objectives To re-evaluate the association of SARS-CoV-2 and development of DKA and analyse the demographic and biochemical parameters and the clinical outcomes in COVID-19 patients with DKA. Design A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed. Methods Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature) were searched from 1 December 2019 to 30 June 2021 in the English language using the following keywords alone or in combination: COVID-19 OR SARS-CoV-2 AND diabetic ketoacidosis OR DKA OR ketosis OR ketonemia OR hyperglycaemic emergency OR hyperglycaemic crisis. We included studies in adults and children of all ages in all healthcare settings. Binary logistic regression model was used to explore the effect of various demographic and biochemical parameters variables on patient’s final treatment outcome (survival or death). Results Of the 484 papers that were identified, 68 articles were included in the systematic review and meta-analysis (54 case report, 10 case series, and 4 cohort studies). Studies involving 639 DKA patients with confirmed SARS-CoV-2 [46 (7.2%) were children and 334 (52.3%) were adults] were analyzed. The median or mean patient age ranged from 1000 mg/dl, and anion gap ≥ 30 mEq/l.

Interaction of Severe Acute Respiratory Syndrome Coronavirus 2 and Diabetes

Article

Full-text available

Oct 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a worldwide epidemic. It spreads very fast and hits people of all ages, especially patients with underlying diseases such as diabetes. In this review, we focus on the influences of diabetes on the outcome of SARS-CoV-2 infection and the involved mechanisms including lung dysfunction, immune disorder, abnormal expression of angiotensin-converting enzyme 2 (ACE2), overactivation of mechanistic target of rapamycin (mTOR) signaling pathway, and increased furin level. On the other hand, SARS-CoV-2 may trigger the development of diabetes. It causes the damage of pancreatic β cells, which is probably mediated by ACE2 protein in the islets. Furthermore, SARS-CoV-2 may aggravate insulin resistance through attacking other metabolic organs. Of note, certain anti-diabetic drugs (OADs), such as peroxisome proliferator-activated receptor γ (PPARγ) activator and glucagon-like peptide 1 receptor (GLP-1R) agonist, have been shown to upregulate ACE2 in animal models, which may increase the risk of SARS-CoV-2 infection. However, Metformin, as a first-line medicine for the treatment of type 2 diabetes mellitus (T2DM), may be a potential drug benefiting diabetic patients with SARS-CoV-2 infection, probably via a suppression of mTOR signaling together with its anti-inflammatory and anti-fibrosis function in lung. Remarkably, another kind of OADs, dipeptidyl Peptidase 4 (DPP4) inhibitor, may also exert beneficial effects in this respect, probably via a prevention of SARS-CoV-2 binding to cells. Thus, it is of significant to identify appropriate OADs for the treatment of diabetes in the context of SARS-CoV-2 infections.

Some characteristics of hyperglycaemic crisis differ between patients with and without COVID-19 at a safety-net hospital in a cross-sectional study

Article

Full-text available

Dec 2021

Objective To compare patients with DKA, hyperglycaemic hyperosmolar syndrome (HHS), or mixed DKA-HHS and COVID-19 [COVID (+)] to COVID-19-negative (−) [COVID (−)] patients with DKA/HHS from a low-income, racially/ethnically diverse catchment area.Methods A cross-sectional study was conducted with patients admitted to an urban academic medical center between 1 March and 30 July 2020. Eligible patients met lab criteria for either DKA or HHS. Mixed DKA-HHS was defined as meeting all criteria for either DKA or HHS with at least 1 criterion for the other diagnosis.Results A total of 82 participants were stratified by COVID-19 status and type of hyperglycaemic crisis [26 COVID (+) and 56 COVID (−)]. A majority were either Black or Hispanic. Compared with COVID (−) patients, COVID (+) patients were older, more Hispanic and more likely to have type 2 diabetes (T2D, 73% vs 48%, p

A practical guidance on the use of intravenous insulin infusion for management of inpatient hyperglycemia

Article

Aug 2021

Background We aim to provide a practical guidance on the use of intravenous insulin infusion for managing inpatient hyperglycemia. Methods and results This document was formulated based on the review of available literature and personal experience of authors. We have used various case scenarios to illustrate variables which should be taken into account when deciding adjustments in infusion rate, including but not restricted to ambient blood glucose level and magnitude of blood glucose change in the previous hour. Conclusion The guidance can be generalised to any situation where dedicated protocols are lacking, trained manpower is not available and resource constraints are present.

Acute hyperglycaemic crisis after vaccination against COVID-19: A case series

Article

Full-text available

Jun 2021

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the most important component of the global response to the COVID-19 pandemic. Although most adverse reactions observed have been mild, the emergence of more serious vaccine-associated adverse events is being closely monitored.

Could Exogenous Insulin Ameliorate the Metabolic Dysfunction Induced by Glucocorticoids and COVID-19?

Article

Full-text available

Jun 2021

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.

Could Dapagliflozin Attenuate COVID-19 Progression in High-Risk Patients With or Without Diabetes? Behind DARE-19 Concept

Article

Apr 2021

Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19 (Coronavirus Disease-2019). Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor (SGLT2i), exerts direct cardioprotective and nephroprotective effects. DARE-19 (Dapagliflozin in Respiratory Failure in Patients With COVID-19), an ongoing clinical trial, is designed to investigate the impact of dapagliflozin on COVID-19 progression. This article discusses the potential favorable impact of dapagliflozin on COVID-19 and its complications.

COVID-19 and diabetes

Article

Sep 2023

Artur Furga

Almost immediately after the emergence of the SARS-CoV-2 coronavirus, it was observed that people with chronic diseases, including diabetes, presented an increased risk of hospitalization and mortality. Diabetes can increase the risk of COVID-associated mortality by more than six times. The hypothesis of a bidirectional relationship between COVID-19 and diabetes assumes that diabetes is a risk factor for worse outcomes of COVID-19 treatment and that coronavirus infection is a predisposing factor for newly diagnosed diabetes or hyperglycemic emergencies. New diagnoses or exacerbations of existing diabetes are associated with direct damage to the pancreas or the body's response to chronic inflammation, and ACE receptors play a large role in this pathomechanism. Restrictions implemented in many countries have resulted in poorer control and underdiagnosis of diabetes. In this review, we summarize the impact of acute COVID-19 on people with diabetes, discuss how presentation and epidemiology changed during the pandemic, and consider the broader impact of the pandemic on patients and healthcare delivery.

The Interplay Between COVID-19 and Pediatric Endocrine Disorders. What have we Learned After More than Three Years of the Pandemic?

Article

Sep 2023

Eirini Kostopoulou

As an increased body of COVID-19 related research is now available, it becomes apparent that the effects of COVID-19 extend beyond that of the respiratory system. Among others, the endocrine system is particularly vulnerable to perturbation from the COVID-19 infection. The present scoping review summarizes the bidirectional relationship between COVID-19 and endocrine system in children and adolescents, by describing both the possible susceptibility of children and adolescents without endocrinopathies to endocrine disorders following COVID-19 infection, but also the potential susceptibility to COVID-19 infection and severe infection, or the aggravation of endocrine dysfunction in patients with pre-existing endocrine diseases. Data suggest increased obesity and diabetes rates, as well as increased severity and frequency of diabetic ketoacidosis following COVID-19 infection. Conversely, patients with diabetes and obesity may experience a more severe course of COVID-19 infection. However, in the majority of cases, children and adolescents with well-managed and regulated endocrine disorders do not appear to be at increased risk of infection or severe infection from COVID-19. Thus, adhering to the appropriate “sick day management rules”, maintaining adequate supply of medications and supplies, keeping close contact with the therapeutic team and seeking medical help without delay when needed, are the main recommendations for a safe outcome. Additional lessons learnt during the pandemic include the risk for mental health diseases caused by children’s disrupted routine due to COVID-19 related protective measures and the importance of adopting alternative communication options, such as telehealth visits, in order to ensure uninterrupted endocrine care.

Diabetic Ketoacidosis and Long-Term Insulin Requirements in Youths with Newly Diagnosed Type 2 Diabetes During the SARS-CoV-2 Pandemic

Article

Jul 2023
Endocr Pract

Objective: SARS-CoV-2 infection increases the risk of diabetes and diabetic ketoacidosis (DKA) in both adults and children. We investigated the clinical course of new-onset type 2 diabetes in obese youth presenting with DKA during the SARS-CoV-2 pandemic. Methods: This single-center retrospective cohort study included 148 obese subjects, aged 10-21 years admitted with DKA from January 2018 to January 2022. Groups were defined by presence of DKA precipitant: Any infection (n=38, 26%), which included the COVID (n=10, 7%) and other infection (n=28, 19%) groups, and no infection (n=110, 74%). Primary outcome was insulin discontinuation within 12-month follow-up. Results: Mean age was 14.9 years (IQR 13.8, 16.5), age-adjusted BMI% was 99.1 (IQR 98.0, 99.5) with 85.8% identifying as Black or Hispanic. There were no differences in DKA severity among groups. Incidence of DKA was higher during the pandemic (March 2020 to January 2022, n=117) compared to pre-pandemic (January 2018 to February 2020, n=31). Within the first year after the acute DKA episode, 46 discontinued all insulin within 9 months (IQR 4,14). Sixteen subjects restarted insulin 10.0 months (IQR 6.5, 11.0) after insulin discontinuation. Infection with SARS-CoV-2 at diagnosis was not associated with likelihood (p=0.57) or timing (p=0.27) of discontinuing all insulin within 1 year, nor was having any infection. Conclusions: The incidence of DKA at onset of type 2 diabetes was higher during the SARS-CoV-2 pandemic than pre-pandemic. SARS-CoV-2 infection was not associated with DKA severity or insulin discontinuation within the first year of diagnosis in youth with new onset type 2 diabetes and DKA.

Management of Critically Ill Persons with COVID-19 and Diabetes

Chapter

Jun 2023

COVID-19 disease poses a significant risk for critical illness, including hyperglycemic emergencies such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), especially in patients with diabetes. While treatment with a continuous insulin infusion is traditionally considered to be the standard of care in DKA management, subcutaneous insulin protocols have been utilized during the pandemic for treating mild-to moderate DKA with the goal of reducing personal protective equipment use, intensive care unit bed utilization, and health-care worker exposure to and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Subcutaneous insulin protocols for DKA generally use an initial basal insulin dose with rapid-acting insulin administered every 3–4 h. Due to the risk for acute respiratory distress syndrome and acute renal injury in COVID-19 disease, judicious fluid and electrolyte management is indicated. To help further reduce the need for potential viral exposure, early data suggests the clinical efficacy and safety of continuous glucose monitoring (CGM) in the management of critically ill patients with COVID-19 disease.KeywordsCOVID-19Intensive care unitDiabetesHyperglycemic emergencyDiabetic ketoacidosisHyperosmolar hyperglycemic syndromeSubcutaneous insulinContinuous glucose monitoring

A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID-19

Article

Apr 2023
DIABETES OBES METAB

Aims: To investigate characteristics of people hospitalised with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission. Materials and methods: Retrospective cohort study with anonymised data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. Primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios (ORs) were calculated using logistic regression. Results: 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalised with COVID-19. Mean(SD) age was 60(18.2)y in DKA and 74(11.8)y in HHS (P < 0.001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% P = 0.038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared to non-users (21.4% vs. 52.2%; age-adjusted OR 0.13 [95%CI 0.03-0.60]). Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, P = 0.001) and in statin users vs non-users (36.4% vs. 100%; P = 0.035) but these were not statistically significant after age adjustment. Conclusions: Hospitalisation with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of prior insulin therapy with survival in type 2 diabetes-associated DKA. This article is protected by copyright. All rights reserved.

COVID-19 as a Trigger for type 1 diabetes

Article

Mar 2023
J CLIN ENDOCR METAB

Type 1 diabetes (T1D) is usually caused by immune-mediated destruction of islet beta-cells, and genetic and environmental factors are thought to trigger autoimmunity. Convincing evidence indicates that viruses are associated with T1D development and progression. During the coronavirus disease 2019(COVID-19) pandemic, cases of hyperglycemia, diabetic ketoacidosis (DKA), and new diabetes increased, suggesting that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may be a trigger for or unmask T1D. Possible mechanisms of beta-cell damage include virus-triggered cell death, immune-mediated loss of pancreatic beta-cells, and damage to beta-cells due to infection of surrounding cells. This article examines the potential pathways by which SARS-CoV-2 affects islet beta-cells in the above three aspects. Specifically, we emphasize that T1D can be triggered by SARS-CoV-2 through several autoimmune mechanisms, including epitope spread, molecular mimicry and bystander activation. Given that the development of T1D is often a chronic, long-term process, it is difficult to currently draw firm conclusions as to whether SARS-CoV-2 causes T1D. This area needs to be focused on in terms of the long-term outcomes. More in-depth and comprehensive studies with larger cohorts of patients and long-term clinical follow-ups are required.

COVID-19 Associated Ketosis and Diabetic Ketoacidosis: A Rapid Review

Article

Feb 2023
DIABETES OBES METAB

SARS-CoV-2 infection could disrupt the endocrine system directly or indirectly, which could result in endocrine dysfunction and glycemic dysregulation, triggering transient or persistent diabetes mellitus (DM). The literature on the complex relationship between COVID-19 and endocrine dysfunctions is still evolving and remains incompletely understood. Thus, we conducted a review on all literature to date involving COVID-19 associated ketosis or diabetic ketoacidosis (DKA). A total of 27 publications were included and analyzed quantitatively and qualitatively. Studies included DKA patients with existing or new onset diabetes. While the number of case and cohort studies was limited, DKA in the setting of COVID-19 seemed to increase risk of death, especially in new onset diabetes patients. Future studies with more specific variables and larger sample sizes are needed to draw better conclusions. This article is protected by copyright. All rights reserved.

Diabetes and the COVID-19 pandemic

Article

Full-text available

Nov 2022
DIABETOLOGIA

Almost immediately after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged, it was evident that people with chronic diseases, including diabetes, were disproportionately affected, with an increased risk of hospitalisation and mortality. Over the ensuing 2 years, the indirect effects of the pandemic on healthcare delivery in the short term have become prominent, along with the lingering effects of the virus in those directly infected. In the wake of the pandemic and without any evidence from high quality studies, a number of national and international consensus recommendations were published, which were subsequently rapidly updated based on observational studies. There have been unprecedented disruptions from both direct and indirect impacts of coronavirus disease-2019 (COVID-19) in people with diabetes. In this review, we summarise the impact of acute COVID-19 in people with diabetes, discuss how the presentation and epidemiology during the pandemic, including presentation of diabetic ketoacidosis and new-onset diabetes, has changed, and we consider the wider impact of the pandemic on patients and healthcare service delivery, including some of the areas of uncertainty. Finally, we make recommendations on prioritising patients as we move into the recovery phase and also how we protect people with diabetes for the future, as COVID-19 is likely to become endemic. Graphical abstract

COVID-19 associated diabetes mellitus: A review

Article

Full-text available

Sep 2022

A significantly higher rate of new-onset diabetes in many coronavirus disease 2019 (COVID-19) patients is a frequently observed phenomenon. The resultant hyperglycemia is known to influence the clinical outcome, thereby increasing the cost of treatment and stay in hospital. This will also affect the post-hospitalization recuperation. It has been observed that new-onset diabetes in COVID-19 patients is associated with considerable increase in morbidity and may be associated with increased mortality in some cases. This mini-review focuses on the possible causes to understand how COVID-19-related diabetes develops, various associated risk factors, and possible mechanism to understand the natural history of the disease process, clinical outcome, associated morbidities and various treatment options in the mana-gement of post COVID-19 diabetes. A literature search was performed in PubMed and other online database using appropriate keywords. A total of 80 articles were found, among which, 53 of the most relevant were evaluated/ analyzed and relevant data were included. The studies show that patients who have had severe acute respiratory syndrome coronavirus 2 infection leading to development of COVID-19 may manifest not only with new-onset diabetes but also worsening of pre-existing diabetes. Cytopathic effect and autoimmune destruction of insulin-secreting pancreatic beta cells, cytokine storm during the active phase of infection causing impaired insulin secretion and resistance, drug-induced hyperglycemia, undetected pre-existing hyperglycemia/diabetic condition, and stress-induced impairment of glucose metabolism are some of the possible potential mechanisms of COVID-19-associated new-onset diabetes mellitus. Many studies published in recent times have found a significantly higher rate of new-onset diabetes mellitus in many COVID-19 patients. Whether it is an inflammatory or immune-mediated response, direct effect of virus or combination of these is unclear. The resultant hyperglycemia is known to influence the clinical outcome and has been associated with considerable increase in morbidity and increased mortality in some cases. Gavkare AM, Nanaware N, Rayate AS, Mumbre S, Nagoba BS. COVID-19 associated diabetes mellitus: A review. World J Diabetes 2022; 13(9): 729-737 [DOI: 10.4239/wjd.v13.i9.729]

Diabetes Mellitus and COVID-19

Chapter

Aug 2022

Coronavirus disease 2019 (COVID-19) has affected millions of people across the world. Clinicians and scientists across the globe need all the information of this pandemic on one platform. Today, it is also necessary to find out the association of COVID-19 with various medical comorbidities, and its effect on vulnerable populations that require special medical attention. This information will be helpful for the management of COVID-19. COVID-19: Effects in Comorbidities and Special Populations is a concise and visual reference for information about this viral disease and its relationship with different medical conditions. The book provides comprehensive knowledge covering COVID-19 comorbidities (for example, CVD, Diabetes, lung diseases, etc.), and the incidence in specific groups (for example, children and the elderly). Chapters outline the features and the management of the disease in specific conditions. Key Features: ✓ 12 chapters covering several aspects of COVID-19 management, making this a perfect text book for virologist and medical students ✓ Focused and structured description of different effects of COVID-19 in specific patient groups ✓ Multiple tables and figures which summarizes and highlight important points ✓ Multiple choice questions for learners ✓ Detailed list of references, abbreviations and symbols This book is an essential reference for practicing and training virologists, pulmonologists, medical students and scientists working in research labs, pharmaceutical and biotechnology industries in connection with the control of COVID-19 infection.

Kann Diabetes durch COVID-19 ausgelöst werden?: Erkenntnisse fast 2 Jahre nach Beginn der Pandemie

Article

Feb 2022

ZUSAMMENFASSUNG Es wurde lange diskutiert, ob COVID-19 zu neu auftretendem Diabetes führen kann. Jedoch jetzt, fast 2 Jahre nach Beginn der Pandemie, haben mehrere Studien berichtet, dass neu auftretender Diabetes mit COVID-19 in Verbindung gebracht wird. Stoffwechselerkrankungen sind mit einem erhöhten Risiko für schweres COVID-19 verbunden und umgekehrt wurden bei COVID-19-Patienten eine neu auftretende Hyperglykämie und Komplikationen eines vorbestehenden Diabetes beobachtet. Darüber hinaus sind leicht erhöhte Blutzuckerwerte bei COVID-19-Patienten selbst bei Menschen ohne Diabetes mit schlechteren Ergebnissen verbunden. Die genauen Mechanismen für einen neu auftretenden Diabetes bei Patienten mit COVID-19 sind noch nicht bekannt. Wahrscheinlich handelt es sich neben direkten oder indirekten Auswirkungen von SARS-CoV-2 auf die Beta-Zellen in der Bauchspeicheldrüse um eine Reihe komplexer zusammenhängender Prozesse, so wie zuvor nicht diagnostizierter Diabetes, Stresshyperglykämie und steroidinduzierte Hyperglykämie.

Metainflammation in COVID-19

Article

Jan 2022

A new coronavirus pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2], has been on the rise. This virus is fatal for broad groups of populations, including elderly, men, and patients with comorbidities among which obesity is a possible risk factor. The pathophysiologic connections between obesity/metainflammation and COVID-19 may be directly related to increasing soluble ACE2 (angiotensin-converting enzyme 2] levels which potentiates the viral entrance into the host cells, or indirectly related to dysregulation of immune system, microvascular injury and hypercoagulability. The SARS-CoV-2 S-glycoprotein interacts mainly with ACE2 or possibly DDP4 receptors to enter into the host cells. The host proteases, especially TMPRSS2 (transmembrane protease serine 2], support the fusion process and virus entry. While membranous ACE2 is considered a port of entry to the cell for SARS-CoV-2, it seems that soluble ACE2 retains its virus binding capability and enhances its entry into the cells. Interestingly, ACE2 on cell membrane may have protective roles by diminishing cytokine storm-related injuries to the organs. Applying medications that can reduce soluble ACE2 levels, antagonizing TMPRSS2 or blocking DDP4 can improve the outcomes of COVID-19. Metformin and statins through immunomodulatory activities, Orlistat by reducing viral replication, and thiazolidinediones by upregulating ACE2 expression have potential beneficial effects against COVID-19. However, the combination of dipeptidyl peptidase-4 (DDP4] inhibitors and spironolactone/eplerenone seems to be more effective by reducing soluble ACE2 level, antagonizing TMPRSS2, maintaining ACE2 on cell membrane and reducing risk of viral entry into the cells.

Diabetic ketoacidosis and high mortality among patients with coronavirus disease 2019 in a Peruvian hospital

Article

Full-text available

Nov 2021

COVID-19-Induced New-Onset Diabetes: Trends and Technologies

Article

Full-text available

Oct 2021

The coronavirus disease 2019 (COVID-19) global pandemic continues to spread worldwide with approximately 216 million confirmed cases and 4.49 million deaths to date. Intensive efforts are ongoing to combat this disease by suppressing viral transmission, understanding its pathogenesis, developing vaccination strategies, and identifying effective therapeutic targets. Individuals with preexisting diabetes also show higher incidence of COVID-19 illness and poorer prognosis upon infection. Likewise, an increased frequency of diabetes onset and diabetes complications has been reported in patients following COVID-19 diagnosis. COVID-19 may elevate the risk of hyperglycemia and other complications in patients with and without prior diabetes history. It is unclear whether the virus induces type 1 or type 2 diabetes or instead causes a novel atypical form of diabetes. Moreover, it remains unknown if recovering COVID-19 patients exhibit a higher risk of developing new-onset diabetes or its complications going forward. The aim of this review is to summarize what is currently known about the epidemiology and mechanisms of this bidirectional relationship between COVID-19 and diabetes. We highlight major challenges that hinder the study of COVID-19-induced new-onset of diabetes and propose a potential framework for overcoming these obstacles. We also review state-of-the-art wearables and microsampling technologies that can further study diabetes management and progression in new-onset diabetes cases. We conclude by outlining current research initiatives investigating the bidirectional relationship between COVID-19 and diabetes, some with emphasis on wearable technology.

SARS‐CoV‐2 as a Potential Cause of Type 1 Diabetes Facilitated by Spike Protein Receptor Binding Domain Attachment to Human Islet Cells: An Illustrative Case Study and Experimental Data

Article

May 2021

Aims To report Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, responsible for Coronavirus Disease 2019 (COVID-19), as a possible cause for type 1 diabetes by providing an illustrative clinical case of a man aged 45 years presenting with antibody-negative diabetic ketoacidosis post-recovery from COVID-19 pneumonia and to explore the potential for SARS-CoV-2 to adhere to human islet cells. Methods Explanted human islet cells from three independent solid organ donors were incubated with the SARS-CoV-2 spike protein receptor biding domain (RBD) fused to a green fluorescent protein (GFP) or a control-GFP, with differential adherence established by flow cytometry. Results Flow cytometry revealed dose-dependent specific binding of RBD-GFP to islet cells when compared to control-GFP. Conclusions Although a causal basis remains to be established, our case and in vitro data highlight a potential mechanism by which SARS-CoV-2 infection may result in antibody-negative type 1 diabetes

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study

Article

Full-text available

Aug 2020
DIABETOLOGIA

Aims/hypothesis: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. Methods: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. Results: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. Conclusions/interpretations: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. Trial registration: clinicaltrials.gov NCT04324736.

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

Article

Full-text available

May 2020
CELL METAB

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.

Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports

Article

Full-text available

Apr 2020

Since the first case was contracted by coronavirus disease-19 (COVID-19) in Daegu, Korea in February 2020, about 6,800 cases and 130 deaths have been reported on April 9, 2020. Recent studies have reported that patients with diabetes showed higher mortality and they had a worse prognosis than the group without diabetes. In poorly controlled patients with diabetes, acute hyperglycemic crises such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) also might be precipitated by COVID-19. Thus, intensive monitoring and aggressive supportive care should be needed to inadequately controlled patients with diabetes and COVID-19 infection. Here, we report two cases of severe COVID-19 patients with acute hyperglycemic crises in Korea.

Ketosis-Prone Diabetes (Flatbush Diabetes): an Emerging Worldwide Clinically Important Entity

Article

Full-text available

Oct 2018
Curr Diabetes Rep

Purpose of Review Ketosis-prone diabetes or Flatbush diabetes has been widely recognized as a clinical entity since 1984. Most of the early clinical studies focused on African American or Afro-Caribbean individuals. It is now being recognized as an important clinical entity in sub-Saharan Africans, Asian and Indian populations, and Hispanic populations. Major questions remain as to its pathogenesis and whether it is a unique type of diabetes or a subset of more severe type 2 diabetes with greater loss of insulin action in target tissues. This review summarizes the main clinical and mechanistic studies to improve the understanding of ketosis-prone (Flatbush) diabetes. Recent Findings Little data are available on the magnitude of KPD in the different susceptible populations. It is relatively common in black populations. KPD is defined as a syndrome in which diabetes commences with ketoacidosis in individuals who are GAD and anti-islet cell antibody negative and have no known precipitating causes. The patients present during middle age, are overweight or mildly obese, and in many reports are more likely to be male. After intensive initial insulin therapy, many patients become insulin independent and can be well controlled on diet alone or diet plus oral medications. Summary The clinical course of KPD is like that of patients with type 2 diabetes rather than that of type 1 diabetes. Little differences are found in the clinical characteristics and clinical outcomes between patients presenting with KPD and those presenting with severe hyperglycemia with no ketoacidosis. The mechanisms responsible for the development of ketosis-prone diabetes as well its remission remain unknown.

Treatment of Diabetic Ketoacidosis (DKA)/Hyperglycemic Hyperosmolar State (HHS): Novel Advances in the Management of Hyperglycemic Crises (UK Versus USA)

Article

Full-text available

Mar 2017
Curr Diabetes Rep

Purpose of Review Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are diabetic emergencies that cause high morbidity and mortality. Their treatment differs in the UK and USA. This review delineates the differences in diagnosis and treatment between the two countries. Recent Findings Large-scale studies to determine optimal management of DKA and HHS are lacking. The diagnosis of DKA is based on disease severity in the USA, which differs from the UK. The diagnosis of HHS in the USA is based on total rather than effective osmolality. Unlike the USA, the UK has separate guidelines for DKA and HHS. Treatment of DKA and HHS also differs with respect to timing of fluid and insulin initiation. Summary There is considerable overlap but important differences between the UK and USA guidelines for the management of DKA and HHS. Further research needs to be done to delineate a unifying diagnostic and treatment protocol.

Hyperglycemic Crises in Adult Patients With Diabetes

Article

Full-text available

Aug 2009

Diabetic ketoacidosis (DKA) and the hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. DKA is responsible for more than 500,000 hospital days per year (1,2) at an estimated annual direct medical expense and indirect cost of 2.4 billion USD (2,3). Table 1 outlines the diagnostic criteria for DKA and HHS. The triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration characterizes DKA. HHS is characterized by severe hyperglycemia, hyperosmolality, and dehydration in the absence of significant ketoacidosis. These metabolic derangements result from the combination of absolute or relative insulin deficiency and an increase in counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Most patients with DKA have autoimmune type 1 diabetes; however, patients with type 2 diabetes are also at risk during the catabolic stress of acute illness such as trauma, surgery, or infections. This consensus statement will outline precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS in adult subjects. It is based on a previous technical review (4) and more recently published peer-reviewed articles since 2001, which should be consulted for further information. View this table: Table 1 Diagnostic criteria for DKA and HHS Recent epidemiological studies indicate that hospitalizations for DKA in the U.S. are increasing. In the decade from 1996 to 2006, there was a 35% increase in the number of cases, with a total of 136,510 cases with a primary diagnosis of DKA in 2006—a rate of increase perhaps more rapid than the overall increase in the diagnosis of diabetes (1). Most patients with DKA were between the ages of 18 and 44 years (56%) and 45 and 65 years (24%), with only 18% of patients <20 years of age. Two-thirds of DKA patients were considered to have type 1 diabetes and …

Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study

Article

Aug 2020

Background Although diabetes has been associated with COVID-19-related mortality, the absolute and relative risks for type 1 and type 2 diabetes are unknown. We assessed the independent effects of diabetes status, by type, on in-hospital death in England in patients with COVID-19 during the period from March 1 to May 11, 2020. Methods We did a whole-population study assessing risks of in-hospital death with COVID-19 between March 1 and May 11, 2020. We included all individuals registered with a general practice in England who were alive on Feb 16, 2020. We used multivariable logistic regression to examine the effect of diabetes status, by type, on in-hospital death with COVID-19, adjusting for demographic factors and cardiovascular comorbidities. Because of the absence of data on total numbers of people infected with COVID-19 during the observation period, we calculated mortality rates for the population as a whole, rather than the population who were infected. Findings Of the 61 414 470 individuals who were alive and registered with a general practice on Feb 16, 2020, 263 830 (0·4%) had a recorded diagnosis of type 1 diabetes, 2 864 670 (4·7%) had a diagnosis of type 2 diabetes, 41 750 (0·1%) had other types of diabetes, and 58 244 220 (94·8%) had no diabetes. 23 698 in-hospital COVID-19-related deaths occurred during the study period. A third occurred in people with diabetes: 7434 (31·4%) in people with type 2 diabetes, 364 (1·5%) in those with type 1 diabetes, and 69 (0·3%) in people with other types of diabetes. Unadjusted mortality rates per 100 000 people over the 72-day period were 27 (95% CI 27–28) for those without diabetes, 138 (124–153) for those with type 1 diabetes, and 260 (254–265) for those with type 2 diabetes. Adjusted for age, sex, deprivation, ethnicity, and geographical region, compared with people without diabetes, the odds ratios (ORs) for in-hospital COVID-19-related death were 3·51 (95% CI 3·16–3·90) in people with type 1 diabetes and 2·03 (1·97–2·09) in people with type 2 diabetes. These effects were attenuated to ORs of 2·86 (2·58–3·18) for type 1 diabetes and 1·80 (1·75–1·86) for type 2 diabetes when also adjusted for previous hospital admissions with coronary heart disease, cerebrovascular disease, or heart failure. Interpretation The results of this nationwide analysis in England show that type 1 and type 2 diabetes were both independently associated with a significant increased odds of in-hospital death with COVID-19. Funding None.

Type 1 and Type 2 Diabetes and COVID-19 Related Mortality in England: A Whole Population Study

Article

Jan 2020

Diabetic ketoacidosis precipitated by Covid-19 in a patient with newly diagnosed diabetes mellitus

Article

Apr 2020
DIABETES RES CLIN PR

Practical recommendation for the management of diabetes in patients with COVID-19

Article

Apr 2020

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.

COVID ‐19 infection may cause ketosis and ketoacidosis

Article

Apr 2020

This study included 658 hospitalized patients with confirmed COVID‐19. Forty‐two (6.4%) out of 658 patients presented with ketosis on admission with no obvious fever or diarrhea. They had a median age of 47.0 years (IQR, 38.0–70.3), while 16 (38.1%) were men. Patients with ketosis were younger (median age: 47.0 vs 58.0 years, P = 0.003) and had greater prevalence of fatigue (31.0% vs 10.6%, P < 0.001), diabetes (35.7% vs 18.5%, P = 0.007), and digestive disorders (31.0% vs 12.0%, P < 0.001). However, they had longer length of hospital stay (19.0 [12.8–33.3] days vs 16.0 [10.0–24.0] days, P < 0.001) and higher mortality rate (21.4% vs 8.9%, P = 0.017). Three (20.0%) out of the 15 cases with diabetic ketosis developed acidosis, 5 cases (26.7%) with diabetic ketosis died, and one (25.0%) of the deaths presented with acidosis. Two (7.4%) and four (14.3%) cases of the 27 non‐diabetic ketotic patients developed severe acidosis and died, respectively, and one (25.0%) of the deaths presented with acidosis. This suggested that COVID‐19 infection caused ketosis or ketoacidosis, and induced DKA for those patients with diabetes. Ketosis increased the length of hospital stay and mortality. Meanwhile, diabetes increased the length of hospital stay for patients with ketosis but had no effect on their mortality. This article is protected by copyright. All rights reserved.

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study

Jan 2020
1500-1515

Cariou B.
Hadjadj S.
Wargny M.
Pichelin M.
Al-Salameh A.
Allix I.
Amadou C.
for the CORONADO investigators

Diabetic ketoacidosis precipitated by Covid-19 in a patient with newly diagnosed diabetes mellitus.

Jan 2020

Chee YJ
Ng SJH
Yeoh E

Protracted ketonaemia in hyperglycaemic emergencies in COVID-19: a retrospective case series

No full-text available

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