Complex presentations in people with diabetes: Does HbA1c help or hinder?

HbA1c measurement is widely used for diagnosis/ management/remission of diabetes with international schemes certifying comparability. A) 75 year-old Chinese female with type 2 diabetes was admitted in April 2020 with Covid-19 and diabetic ketoacidosis. Glucose was 35mmol/l and HbA1c 150mmol/mol with previous HbA1c of 45mmol/mol on metformin and alogliptin. She was treated for ketoacidosis and once-daily Lantus introduced along with supportive management of viral illness. B) 68 year-old Afro-Caribbean with type 2 diabetes on metformin before admission, presented with new onset, jerky ballistic movements of high amplitude in right arm, 10-15 movements every 5 min. Admission glucose was >33mmol/l, ketones 1.8mmol/l and HbA1c >217mmol/ mol. Hemichorea-hemiballism, a hyperglycaemia related movement was diagnosed and insulin commenced. Glucose decreased to 8-20mmol/ l, reaching 5-15mmol/ l by time of discharge. Ballistic movements resolved when glycaemic control improved with HbA1c 169mmol/mol, 25 days after discharge. C) Several days before admission, a female with diabetes over 20 years required attention from paramedics on four occasions for hypoglycaemia. Months beforehand metformin was replaced by gliclazide due to chronic kidney disease with HbA1c 50mmol/mol, and she was transfused six weeks before admission for microcytic anaemia. Gliclazide was discontinued and her diet modified which prevented further hypoglycaemic episodes. Variant haemoglobin, beta-thalassaemia which can overestimate glycaemia;undetected by HbA1c HPLC method, invalidated HbA1c as did the blood transfusion. These cases highlight that inadequate understanding of HbA1c can lead to acute presentations of dysglycaemia. As HbA1c accuracy can be affected by multiple factors, clinical assessment and triangulation are key to the management of such patients.

Infectious bronchitis virus infection in chicken: viral load and immune responses in Harderian gland, choanal cleft and turbinate tissues compared to trachea.

1. The role of the Harderian gland (HG), choanal cleft (CC) and turbinate in terms of IBV M41 viral load compared to the trachea, and immune (innate, cellular and mucosal) responses were studied in 21-day-old commercial broiler chickens.2. After virulent IBV M41 challenge, the antigen concentration detected either by quantitative RT-PCR or immunohistochemistry peaked at 2-3 days post challenge (dpc) in all tissues. Significant increases of lachrymal IBV-specific IgA and IgY levels were found at 4-5 dpc.3. Gene transcription showed a significant up-regulation of TLR3, MDA5, IL-6, IFN-α and IFN-ß, where patterns and magnitude fold-change of mRNA transcription were dependent on the gene and tissue type.4. The results demonstrated active IBV M41 replication in the HG, CC and turbinate, comparable to levels of replication found in the trachea. Data on immune-related genes in head-associated tissues provide further understanding on the immunobiology of IBV and offer opportunities to identify their use as quantitative biomarkers in pathogenicity and vaccination-challenge studies.

Service analysis examining the outcomes based on dexamethasone duration in Covid patients requiring oxygen in UKhospital

Background: Recent RECOVERY trial showed use of dexamethasone lead to reduction in 28 days mortality in patients with COVID pneumonia requiring oxygen. NICE recommends offering dexamethasone for 10 days in patients with COVID positive pneumonia. However, outcomes from real world data are lacking. Aim: The aim of this study was to analyse the impact of different duration of dexamethasone on mortality rate in patients with COVID positive pneumonia requiring oxygen. Method: The study was performed retrospectively from single centre using electronic PICS (prescribing information and communication system). We included patients admitted in hospital between the periods of 29/12/2020 to 7/1/2021 with diagnosis of COVID pneumonia, requiring dexamethasone. Data extracted included patient demographics, diabetes status and number of days on dexamethasone. We evaluated outcomes in three groups based on duration of dexamethasone as Group A (10 days), Group B (4-9 days) and Group C (≤3 days). Primary outcomes were mortality rate and length of stay. Results: We identified 179 patients. Mean (SD) age was 65 (17) years, 45.8% were female. Mean BMI was 31(14) kg/m2, 56.9% were Caucasian, 18.9% South Asian,4.4% were Afro-Caribbean,46.9% had diabetes. 128 patients were nursed on general medical ward (GIM) and 51 patients needed ITU setting. The mortality rate was 25 %, 20% and 43.7% in group A, B and C respectively. Mean length of stay (LOS) was 9 (11) days,10 (7) days and 9 (6) days in group A, B and C respectively. Further analysis of patients nursed on GIM ward showed mortality rate of 11.9%, 25% and 66.6% in group A, B and C suggesting an association between longer duration of dexamethasone and reduction in mortality. No difference in LOS was noted. No similar analysis was conducted in patients nursed on ITU setting because of small sample size. Discussion: Longer duration of dexamethasone was associated with better mortality rate in patients nursed on GIM ward and hence we should offer full course of 10 days dexamethasone in patients admitted with Covid pneumonia requiring oxygen. However, our study had small sample size, from single centre and result was not adjusted for co-variables like age, gender, BMI, and amount of oxygen requirement. We need future study with large sample size, multicentre and addressing these limitations.

An audit on the use of variable rate intravenous insulin infusions (VRIII) in patients diagnosed with SARS-CoV-2

Aims: To assess VRIII utilisation in SARS-CoV-2 positive patients with diabetes mellitus at Queen Elizabeth Hospital, Birmingham, and adherence to Joint British Diabetes Society (JDBS) standards. Methods: This was a retrospective data-based study. All patients admitted to Queen Elizabeth Hospital Birmingham who tested positive for SARS-CoV-2 requiring VRIII between March and June 2020 were included in the study. Data were extracted using our electronic database Prescribing Information and Communication System (PICS). Data were collected on demographics, diabetic history and VRIII use. Primary outcome measures were substrate use, diabetes medication management, glycaemic control, adverse events as analysed by rate of hypoglycaemia, hyponatraemia and hypokalaemia and monitoring of renal function and capillary blood glucose, in accordance with the JDBS guidelines. Pre-planned subset analysis was performed based on the patient location (ward or intensive care unit (ICU)). All results are shown as median±SD. Results: A total of 85 patients were included in the study, with 55 patients treated in the ICU and 28 patients treated on the wards. The median age of ICU patients was lower than those on the wards (57±10.23 years vs 71.5±16.81 years) and BMI was higher (29.7±6.56 kg/m2 vs 27.8±6.43 kg/m2). The percentage of male patients in ICU was higher compared with those on the wards (76.4% (42/55) vs 53.6% (15/28)). The substrate was used appropriately in 53.3% of VRIII episodes on the ward compared with only 5.4% on ICU. This was due to the concomitant use of NG feeds in 90%. Daily monitoring of electrolytes whilst on a VRIII was higher in the ICU (94.5%, 52/55) than on the ward (71.42%, 21/28). Long-acting insulin was continued in 100% of all type 1 diabetes in both wards and ICU. Median VRIII duration was higher in ICU, given prolonged stay and patients being more unwell, than on the ward (233±184.32 hours vs 14.5±52.26 hours). Target glycaemic control whilst on VRIII was better achieved in the ICU than on the wards. Conclusion: Intensive care with close monitoring has demonstrated better adherence to VRIII as outlined by JBDS for management of hyperglycaemia in patients with diabetes and COVID-19. The longer use of VRIII in unwell ICU patients may reflect higher insulin insensitivity. A further interventional multicentre study is required to gain further insight.

Demographics, management and outcomes of inpatients with newly diagnosed diabetes in acute covid-19 infection

Aim: To investigate the demographics, management and outcomes of patients with newly diagnosed diabetes in covid-19 infection admitted to Queen Elizabeth Hospital, Birmingham. Methods: All patients with a new diagnosis of diabetes on their admission with covid-19 pneumonia (pre-dexamethasone use) between March and June 2020 were examined. Demographics, comorbidities, medication history, investigations, management and outcomes were analysed. Results: Twelve patients were identified. Demographic analysis revealed (all median [IQR]);Age 59.5 [51.5-69.3] years, body mass index 27.4 [26.0-28.9] kg/m2 and length of admission 21.5 [7.5-28.8] days. The majority of patients were male (9/12) and most were diagnosed with type 2 diabetes (9/12). Seven patients had no diabetes symptoms prior to admission and positive family history was uncommon (1/12). Median glucose reading on admission was 16.0 [10.0-29.0] mmol/l, HbA1c 62.5 [47-104] mmol/mol. During admission, median percentage of glucose in target (5-15 mmol/l) for individual patients was 71.6 [46.4-91.0]% and median percentage of glucose levels in hypoglycaemic range (<4 mmol/l) was 0.8 [0.0-2.6]%. Intravenous insulin was required by half of patients (6/12). 5/12 (41.7%) patients were admitted to the critical care unit versus 69/497 (13.8%) patients with pre-existing diabetes and covid-19, median length of stay was 18.5 [13.3-23.0] days versus 7 [3-13] days. 3/12 patients died during admission (25.0%) versus 112/497(23%) patients with pre-existing diabetes and covid-19. Of the nine patients discharged, six required long-term antidiabetes therapy;five with insulin and one with oral diabetic treatment. Conclusion: A new diagnosis of diabetes in combination with covid-19 infection is associated with high rates of complication relating to glucose control and need for intensive care during admission.

Immunopathogenesis of infectious bronchitis virus Q1 in specific pathogen free chicks.

The immunopathogenesis of avian coronavirus, infectious bronchitis virus (IBV) Q1, was investigated in specific pathogen free chicks. Following infection, chicks exhibited respiratory clinical signs and reduced body weight. Oropharyngeal (OP) and cloacal (CL) swabs were collected at intervals and found to be RT-PCR positive, with a greater number of partial-S1 amino acid changes noted in CL swabs compared to OP swabs. In tissue samples, IBV viral load peaked 9 days post infection (dpi) in the trachea and kidneys, and 14 dpi in the proventriculus. At 28 dpi, ELISA data showed that 63% of infected chicks seroconverted. There was significantly higher mRNA up-regulation of IFN-α, TLR3, MDA5, LITAF, IL-1ß and IL-6 in the trachea compared to the kidneys. Findings presented here demonstrate that this Q1 isolate induces greater lesions and host innate immune responses in chickens' tracheas compared to the kidneys.