Diabetic ketoacidosis precipitated by COVID-19: A report of two cases and review of literature.

BACKGROUND AND AIMS: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) and diabetes mellitus is bidirectional. On one hand, diabetes mellitus is associated with an increased risk of severe COVID-19. On the other hand, new onset diabetes and severe metabolic complications of pre-existing diabetes, including diabetic ketoacidosis (DKA) have been observed in patients with COVID-19. In this report, we describe two patient with diabetes mellitus who presented to our hospital with DKA. We also reviewed almost all published cases of DKA that had been precipitated by COVID-19. METHODS: Two patients were admitted with DKA, who were diagnosed to have COVID-19 on the basis of real time reverse transcription-polymerase chain reaction (RT-PCR) assay. Detailed history, anthropometry, laboratory investigations, imaging studies, clinical course and management outcomes were documented. RESULTS: First patient (30-year-male) had undiagnosed diabetes and no other comorbidities, and COVID-19 precipitated DKA. He also had COVID-19-associated pneumonia. Second patient (60-year-male) had long duration hypertension with no prior history of diabetes and developed cerebrovascular accident (CVA). He was also diagnosed with COVID-19 (RT-PCR assay) and DKA in the hospital. CVA and COVID-19 could have precipitated DKA. Both patients responded well to treatment and were discharged in a stable condition. CONCLUSIONS: These cases show that COVID-19 can precipitate DKA in a significant number of patients. DKA can occur in patients with pre-existing diabetes or newly diagnosed diabetes. As COVID-19 and diabetes are prevalent conditions, high degree of suspicion is required to diagnose DKA timely in order to improve the prognosis of COVID-19-related diabetic ketoacidosis.

Has COVID-19 Delayed the Diagnosis and Worsened the Presentation of Type 1 Diabetes in Children?

OBJECTIVE: To evaluate whether the diagnosis of pediatric type 1 diabetes or its acute complications changed during the early phase of the coronavirus disease 2019 (COVID-19) pandemic in Italy. RESEARCH DESIGN AND METHODS: This was a cross-sectional, web-based survey of all Italian pediatric diabetes centers to collect diabetes, diabetic ketoacidosis (DKA), and COVID-19 data in patients presenting with new-onset or established type 1 diabetes between 20 February and 14 April in 2019 and 2020. RESULTS: Fifty-three of 68 centers (77.9%) responded. There was a 23% reduction in new diabetes cases in 2020 compared with 2019. Among those newly diagnosed patients who presented in a state of DKA, the proportion with severe DKA was 44.3% in 2020 vs. 36.1% in 2019 (P = 0.03). There were no differences in acute complications. Eight patients with asymptomatic or mild COVID-19 had laboratory-confirmed severe acute respiratory syndrome coronavirus 2. CONCLUSIONS: The COVID-19 pandemic might have altered diabetes presentation and DKA severity. Preparing for any "second wave" requires strategies to educate and reassure parents about timely emergency department attendance for non-COVID-19 symptoms.

High prevalence of COVID-19-associated diabetic ketoacidosis in UK secondary care.

We aim to describe the prevalence of diabetic ketoacidosis (DKA) in individuals admitted to a single centre with COVID-19. We identified 218 individuals hospitalised with COVID-19, of these four fulfilled criteria for DKA (4/218, 1.8%). We conclude DKA is common and severe in individuals hospitalised with COVID-19.

Diabetic Ketoacidosis in COVID-19: Unique Concerns and Considerations.

CONTEXT: While individuals with diabetes appear to be at similar risk for SARS-CoV-2 infection to those without diabetes, they are more likely to suffer severe consequences, including death. Diabetic ketoacidosis (DKA) is a common and potentially lethal acute complication of diabetes arising from a relative insulin deficiency, which occurs more often in those with type 1 diabetes and in the setting of moderate to severe illness. Early reports indicate that among patients with pre-existing diabetes, DKA may be a common complication of severe COVID-19 and a poor prognostic sign. CASE DESCRIPTION: This clinical perspective explores the key elements of caring for individuals with DKA during the COVID-19 pandemic through 2 cases. Topics addressed include diagnosis, triage, and the fundamental principles of treatment with a focus on the importance of characterizing DKA severity and medical complexity to determine the best approach. CONCLUSIONS: As discussed, some tenets of DKA management may require flexibility in the setting of COVID-19 due to important public health goals, such as preventing transmission to highest risk individuals, reducing healthcare worker exposure to infected patients, and preserving personal protective equipment. Evidence for alternative treatment strategies is explored, with special attention placed on treatment options that may be more relevant during the pandemic, including use of subcutaneous insulin therapy. Finally, DKA is often a preventable condition. We include evidence-based strategies and guidance designed to empower clinicians and patients to avoid this serious complication when possible.

COVID-19 in diabetic patients: Related risks and specifics of management.

Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.

Uncommon Association Between Diabetic Ketoacidosis, Thyrotoxicosis, Cutaneous Abscess and Acute Pericarditis in an Immunocompetent Patient: A Single Case Report and Literature Review.

INTRODUCTION: The typical factors precipitating diabetic ketoacidosis (DKA) include infections (30%), cessation of antidiabetic medication (20%), and a new diagnosis of diabetes (25%). The etiology remains unknown in 25% of cases. Less frequent causes cited in the literature include severe thyrotoxicosis and, infrequently, pericarditis. Few publications have described the role of human T lymphotropic virus type 1 (HTLV-1) in endocrine and metabolic disorders. Based on a clinical case associated with several endocrine and metabolic disorders, we suggest a potential role for HTLV-1, an endemic virus in the Amazonian area, and review the literature concerning the role of this virus in thyroiditis, pericarditis and diabetes mellitus. CASE REPORT: A fifty-year-old Surinamese woman without any medical history was admitted for diabetic ketoacidosis. No specific anti-pancreatic autoimmunity was observed, and the C-peptide level was low, indicating atypical type-1 diabetes mellitus. DKA was associated with thyrotoxicosis in the context of thyroiditis and complicated by nonbacterial pericarditis and a Staphylococcus aureus subcutaneous abscess. The patient was infected with HTLV-1. CONCLUSION: To our knowledge, this uncommon association is described for the first time. Few studies have analyzed the implications of HTLV-1 infection in thyroiditis and diabetes mellitus. We did not find any reports describing the association of pericarditis with HTLV-1 infection. Additional studies are necessary to understand the role of HTLV-1 in endocrine and cardiac disorders.

Relationship between HHV8 infection markers and insulin sensitivity in ketosis-prone diabetes.

BACKGROUND AND OBJECTIVES: Peripheral tissue resistance to insulin action is a characteristic of type 2 diabetes mellitus (T2DM). It has also been reported that some chronic viral infections can contribute to insulin resistance. Human herpesvirus (HHV)-8 infection has been detected in T2DM patients in previous studies. Our study investigated whether the presence of the virus is associated with insulin resistance in patients with ketosis-prone type 2 diabetes (KPD), as reported with other viruses. RESEARCH DESIGN AND METHODS: A total of 11 insulin-free KPD patients positive (+) and seven patients who were negative (-) for HHV-8 infection were recruited; the latter had KPD that was well controlled (HbA1c=6.2±0.7%). A two-step euglycaemic-hyperinsulinaemic clamp test coupled with deuterated [6,6-2H2]glucose was used to assess insulin sensitivity, non-esterified fatty acid (NEFA) suppression and endogenous glucose production. RESULTS: In KPD patients, whether HHV-8+ or HHV-8-, there were no differences in NEFA release, endogenous glucose production or insulin sensitivity (M value). CONCLUSION: Asymptomatic HHV-8 infection does not appear to be associated with decreased insulin sensitivity in diabetic patients. These results should now be confirmed in a larger sample population.

Diabetic ketoacidosis following mumps.

A-13-year-old girl presented with diabetic ketoacidosis with convincing clinical signs of parotitis (fever, drooling of saliva, inability to swallow with development of bilateral parotid swelling) and pancreatitis (fever, abdominal pain and vomiting), along with high serum amylase and positive mumps IgM titer. This suggests that mumps virus may have been the causative factor, probably as a result of concomitant involvement of the pancreas.

H1N1 influenza infection complicated with diabetic ketoacidosis.

The 2009 H1N1 Influenza virus was the first infectious pandemic of the 21(st) century which spread rapidly throughout the world. High-risk groups, such as diabetics, suffered more and showed higher hospital admission and death rates due to this virus. Patients with diabetes mellitus (DM) may develop the fulminant picture of their disease after being infected with influenza. From June to December 2009 at Nemazee Hospital, affiliated with Shiraz University of Medical Sciences, two patients with diabetic ketoacidosis (DKA) were admitted. The H1N1 influenza virus triggered DKA and its complications in these patients. Both patients were female, of ages 16 and 40 years. When admitted, they had signs of influenza-like illness (ILI), tachypnea, laboratory confirmation of acidosis, and high blood sugar levels. The 2009 H1N1 influenza viral RNA was detected in their nasopharyngeal specimens by real time polymerase chain reaction (RT-PCR). Both patients received oseltamivir, but eventually both died. This was the first report of an association between DKA and H1N1 influenza in Iran. Conclusively, rapid diagnosis of influenza by RT-PCR and early treatment with oseltamivir should be considered in diabetics and/or DKA patients with flu-like symptoms.

Development of fulminant Type 1 diabetes with thrombocytopenia after influenza vaccination: a case report.

BACKGROUND: Fulminant Type 1 diabetes was originally reported as idiopathic Type 1 diabetes. Involvement of viral infections in the pathogenesis of fulminant T1D has been suggested, but the development of fulminant Type 1 diabetes after influenza vaccination has not been reported. CASE REPORT: We report a case of fulminant Type 1 diabetes with thrombocytopenia following influenza vaccination. A 54-year-old man was admitted to hospital with hyperglycaemia and diabetic ketosis. Seven days before admission, he received a seasonal influenza vaccine for the prevention of influenza infection. On admission, blood glucose was 29 mmol/L and HbA1c 40 mmol/mol (5.9%). Fasting and 2-h C-peptide immunoreactivity were <0.0333 nmol/L and 0.0999 nmol/L, respectively. Anti-GAD and anti-IA-2 antibodies were negative, so no autoimmunity seemed to participate in the etiology. ELISPOT assay also showed no association with T cell-mediated autoimmunity. HLA genotypes were consistent with susceptibility to fulminant Type 1 diabetes. After the abrupt onset of diabetes, he showed mild thrombocytopenia, which has been observed for approximately 5 years after diabetes development. CONCLUSION: This is the first description of fulminant Type 1 diabetes after influenza vaccination. Our observation raises the possibility that influenza vaccination might trigger this condition via the TLR7 pathway.

H1N1 influenza: the trigger of diabetic ketoacidosis in a young woman with ketosis-prone diabetes.

In this study, the authors report a case of new-onset ketosis-prone diabetes in a 21-year-old Chinese woman with H1N1 influenza, who presented with fever, polyuria and loss of appetite for 3 days before admission. She was hospitalized and diagnosed with acute-onset diabetic ketoacidosis for the first time. Her diabetes-associated antibodies were negative. Interestingly, she had an unexplained fever and her white blood cell count was low at admission and remained low for several days. She was believed to have a viral infection, which was found to be H1N1 influenza infection. The literature regarding virus infection and diabetic ketoacidosis is reviewed. The precipitating factors, symptomatology, pathophysiology and management of ketosis-prone diabetes are discussed in the current case report.

A case of fulminant type 1 diabetes mellitus accompanied by myocarditis.

This report presents the case of a 47-year-old female patient with fulminant type 1 diabetes mellitus and myocarditis. Following a high fever, nausea, vomiting and diarrhea, diabetic ketoacidosis occurred and she was transferred to the hospital. The plasma glucose level was 63.6 mmol/L and HbA1c was 7.0%. C-peptide was undetectable in her plasma. Blood gas analysis showed a pH of 6.99. Antibodies to glutamic acid decarboxylase nor insulinoma associated antigen-2 were not detected. She was diagnosed to have fulminant type 1 diabetes mellitus. Her electrocardiogram showed diffuse ST-segment elevations on the second day of admission, along with a positive troponin test. However coronary angiography revealed neither occlusion nor stenosis of the cardiac arteries. An endomyocardial biopsy revealed hypertrophic cardiomyocytes with a disarrangement of myofibers and the focal accumulation of mononuclear cells in the stroma, thus suggesting myocarditis or mild myocarditic change. Viruses are an important cause of myocarditis and the preceding flu-like symptoms indicate the association of viral infection with myocarditis in this case. The mechanisms by which fulminant type 1 diabetes mellitus occurs is still uncertain, but the presence of islet injury accompanied by myocardial inflammation in the current case suggested that a viral infection accounted for the onset of this type of diabetes.

A case of fulminant type 1 diabetes associated with significant elevation of mumps titers.

Type 1 diabetes mellitus is classified as either autoimmune or idiopathic. Fulminant type 1 diabetes was originally reported as a subtype of idiopathic type 1 diabetes. Though involvement of viral infections has been suggested as a triggering mechanism, its pathogenesis remains unknown. Here, we present a case of fulminant type 1 diabetes associated with significant elevation of mumps titers. A 56-year-old Japanese man had suffered from nausea and generalized fatigue for two days before being transferred to our hospital in a confused state. Findings on admission revealed a high blood glucose level, near-normal HbA1c level, metabolic acidosis, and increased urinary ketone levels. Serum tests for islet-associated autoantibodies were negative. The serum, urinary C-peptide levels and the result of glucagon test indicated severe impairment of insulin secretion. These results were compatible with the diagnosis of fulminant type 1 diabetes. Also, he was suspected as having mumps infection on the basis of serological testing. These findings suggest that fulminant type 1 diabetes developed after mumps virus infection in our case. To the best of our knowledge, no other report has indicated an association between a recent mumps infection and the onset of fulminant type 1 diabetes. This case suggests an association between fulminant type 1 diabetes and mumps virus infection.

Ketosis-prone type 2 diabetes mellitus and human herpesvirus 8 infection in sub-saharan africans.

CONTEXT: An atypical form of type 2 diabetes mellitus (DM-2) is revealed by ketosis (ketosis-prone type 2 diabetes mellitus), frequently occurring in individuals who are black and of African origin, and characterized by an acute onset requiring transient insulin therapy. Its sudden onset suggests precipitating factors. OBJECTIVE: To investigate the putative role of human herpesvirus 8 (HHV-8) in the pathogenesis of ketosis-prone DM-2. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study in which antibodies were searched against latent and lytic HHV-8 antigens using immunofluorescence. The presence of HHV-8 in genomic DNA was investigated in 22 of the participants at clinical onset of diabetes. We also tested whether HHV-8 was able to infect human pancreatic beta cells in culture in vitro. The study was conducted at Saint-Louis University Hospital, Paris, France, from January 2004 to July 2005. All participants were black and of African origin: 187 were consecutive diabetic patients of whom 81 had ketosis-prone DM-2 and 106 had nonketotic DM-2, and 90 individuals were nondiabetic control participants who were matched for age and sex. MAIN OUTCOME MEASURES: Seroprevalence of HHV-8 and percentage of patients with HHV-8 viremia at onset in ketosis-prone DM-2. RESULTS: HHV-8 antibodies were found in 71 patients (87.7%) with ketosis-prone DM-2 vs 16 patients (15.1%) with nonketotic DM-2 (odds ratio, 39.9; 95% confidence interval, 17.1-93.4; P < .001) and 36 of the control participants (40.0%) (odds ratio, 10.7; 95% confidence interval, 4.9-23.4; P < .001). HHV-8 in genomic DNA was present in 6 of 13 patients with ketosis-prone DM-2 tested at acute onset and in 0 of 9 patients with nonketotic DM-2. HHV-8 proteins were present in human islet cells that were cultured for 4 days in the presence of HHV-8. CONCLUSIONS: In this preliminary cross-sectional study, the presence of HHV-8 antibodies was associated with ketosis-prone DM-2 in patients of sub-Saharan African origin. Longitudinal studies are required to understand the clinical significance of these findings.

High titres of IgA antibodies to enterovirus in fulminant type-1 diabetes.

AIMS/HYPOTHESIS: We have recently proposed that fulminant type-1 diabetes is a novel subtype of type-1 diabetes with abrupt onset of insulin-deficient hyperglycaemia without islet-related autoantibodies. The pathogenesis is still unknown, but flu-like symptoms are frequently observed before the onset of disease of this subtype. Enterovirus infection is a candidate environmental factor causing type-1 diabetes. The aim of this study was to determine whether enterovirus infection contributes to the development of fulminant type-1 diabetes. METHODS: We investigated 19 patients with recent-onset fulminant type-1 diabetes, 18 patients with recent-onset typical type-1A diabetes, and 19 healthy controls. IgM, IgG, and IgA subclasses of antibodies to enterovirus were determined by ELISA. RESULTS: IgA antibody titres to enterovirus were significantly higher in fulminant type-1 diabetes than in typical type-1A diabetes (p=0.033) and controls (p=0.0003). IgM antibodies to enterovirus were not detected in any subject. IgG titres were lower in autoimmune diabetes than fulminant type and controls (p=0.014 and 0.019, respectively). CONCLUSIONS/INTERPRETATION: High titres of enterovirus IgA antibodies in serum suggest recurrent enterovirus infection in fulminant type-1 diabetic patients, indicating higher susceptibility to enteroviral infections among them. Such infections might have pathogenetic importance in the triggering of fulminant type-1 diabetes.

Rate and prediction of infection in children with diabetic ketoacidosis.

The purpose of this retrospective cohort study was to determine the rate and prediction of infection in children, < or = 21 years, with diabetic ketoacidosis (DKA). Over a 6-year period, 247 admissions were identified. There were 171 (69%) with no infection, 44 (17.8%) with presumed viral infection, and 32 (12.9%) with bacterial infection. The mean WBC for all patients was 17,519 ( +/- 9,582). 118 (50%) had leukocytosis as defined by a WBC > or = 15,000/mm3. WBC, differential, leukocytosis, as well as sex, temperature and new onset diabetes, were not significant predictors (P > .05) of bacterial infection. Bacterial infections were more common in children < or = 3 years of age (P = .03). There was a significant correlation of WBC with both pH (r = -0.59, P < .001) and bicarbonate (r = -0.43, P < .001). In conclusion, most children in DKA have no evidence of infection. Leukocytosis is common but most likely reflects the severity of DKA rather than the presence of infection.

Coxsackie B virus infection and beta cell autoantibodies in newly diagnosed IDDM adult patients.

BACKGROUND: Environmental agents such as viruses have been identified as potentially important determinants of insulin-dependent diabetes mellitus (IDDM). Enterovirus infections, Coxsackievirus B especially, could be linked to the beta cell damaging process and to the onset of clinical IDDM. OBJECTIVES: Enteroviral (EV) infection and beta cell autoimmunity were studied in adult patients at the onset of IDDM. STUDY DESIGN: A total of 14 newly diagnosed-IDDM patients with ketosis or ketoacidosis were compared to, anteriorly diagnosed IDDM patients with metabolic decompensation, non-IDDM patients with metabolic decompensation and healthy adults. EV infection was studied by genomic RNA detection in whole blood using a RT-PCR assay. In order to assess the level of beta cell autoantibodies at the time of the initial metabolic decompensation, serum specimens from IDDM patients were tested for GAD65 antibodies and islet cell antibodies (ICAs). RESULTS: Coxsackie B3 or B4 virus genome was detected and genotyped in five of 14 (35.7) newly diagnosed IDDM patients and in one of 12 (8%) patients in the course of IDDM. By contrast, none of the 12 non-IDDM patients and none of the 15 healthy adults was positive for enterovirus RNA detection in whole blood. Positive GAD65 antibodies and ICAs assays were not significantly correlated to a positive EV-RNA detection. CONCLUSION: The present study demonstrates that Coxsackie B virus RNA sequences can be detected in the peripheral blood from adult patients at the onset or in the course of IDDM and suggests that a Coxsackie B virus infection could initiate or accelerate beta cell autoimmune damaging process.