Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group.

Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency associated with high mortality. It occurs less frequently than diabetic ketoacidosis (DKA), affects those with pre-existing/new type 2 diabetes mellitus and increasingly affecting children/younger adults. Mixed DKA/HHS may occur. The JBDS HHS care pathway consists of 3 themes (clinical assessment and monitoring, interventions, assessments and prevention of harm) and 5 phases of therapy (0-60 min, 1-6, 6-12, 12-24 and 24-72 h). Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg using [(2×Na+ ) + glucose+urea], marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L. Aims of the therapy are to improve clinical status/replace fluid losses by 24 h, gradual decline in osmolality (3.0-8.0 mOsm/kg/h to minimise the risk of neurological complications), blood glucose 10-15 mmol/L in the first 24 h, prevent hypoglycaemia/hypokalaemia and prevent harm (VTE, osmotic demyelination, fluid overload, foot ulceration). Underlying precipitants must be identified and treated. Interventions include: (1) intravenous (IV) 0.9% sodium chloride to restore circulating volume (fluid losses 100-220 ml/kg, caution in elderly), (2) fixed rate intravenous insulin infusion (FRIII) should be commenced once osmolality stops falling with fluid replacement unless there is ketonaemia (FRIII should be commenced at the same time as IV fluids). (3) glucose infusion (5% or 10%) should be started once glucose <14 mmol/L and (4) potassium replacement according to potassium levels. HHS resolution criteria are: osmolality <300 mOsm/kg, hypovolaemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state and blood glucose <15 mmol/L.

Managing hyperglycaemia during antenatal steroid administration, labour and birth in pregnant women with diabetes - an updated guideline from the Joint British Diabetes Society for Inpatient Care.

This article summarises the Joint British Diabetes Societies for Inpatient Care guidelines on the management of glycaemia in pregnant women with diabetes on obstetric wards and delivery units, Joint British Diabetes Societies (JBDS) for Inpatient Care Group, ABCD (Diabetes Care) Ltd. The updated guideline offers two approaches - the traditional approach with tight glycaemic targets (4.0-7.0 mmol/L) and an updated pragmatic approach (5.0-8.0 mmol/L) to reduce the risk of maternal hypoglycaemia whilst maintaining safe glycaemia. This is particularly relevant for women with type 1 diabetes who are increasingly using Continuous Glucose Monitoring (CGM) and Continuous Subcutaneous Insulin Infusion (CSII) during pregnancy. All women with diabetes should have a documented delivery plan agreed during antenatal clinic appointments. Hyperglycaemia following steroid administration can be managed either by increasing basal and prandial insulin doses, typically by 50% to 80%, or by adding a variable rate of intravenous insulin infusion (VRIII). Glucose levels, either capillary blood glucose or CGM glucose levels, should be measured at least hourly from the onset of established labour, artificial rupture of membranes or admission for elective caesarean section. If intrapartum glucose levels are higher than 7.0 or 8.0 mmol/L on two consecutive occasions, VRIII is recommended. Hourly capillary blood glucose rather than CGM glucose measurements should be used to adjust VRIII. The recommended substrate fluid to be administered alongside a VRIII is 0.9% sodium chloride solution with 5% glucose and 0.15% potassium chloride (KCl) (20 mmol/L) or 0.3% KCl (40 mmol/L) at 50 ml/hr. Both the VRIII and CSII rates should be reduced by at least 50% after delivery.

Vitamin D levels and mortality with SARS-COV-2 infection: a retrospective two-centre cohort study.

BACKGROUND: The role of vitamin D in increased mortality with SARS-COV-2 virus, namely, COVID-19, remains uncertain. We analysed all the patients who were treated as COVID-19-positive with or without a positive swab and were tested for vitamin D levels. METHODS: This was a retrospective, study involving 1226 patients swabbed for SARS-CoV-2 between the 10 February 2020 and 1 May 2020 at two hospitals of East Sussex Healthcare NHS Trust. Patients who were swab-positive for COVID-19 or treated as COVID-19-positive on clinical grounds even though swab results were negative were included in this study. We analysed the association of vitamin D levels and mortality, assessing linear and non-linear associations. RESULTS: A total of 1226 patients had SARS-CoV-2 RNA swabs in this period with age range from 1 year to 101 years. A cohort of 433 of these patients had swabs and recent vitamin D levels anytime in the previous 3 months. Mortality rates were not found to be associated with vitamin D levels (OR=1.04, 95% CI 0.96 to 1.12). CONCLUSION: Our findings suggest similar mortality risk from COVID-19 irrespective of the levels of vitamin D. Larger prospective studies will be needed to confirm these findings.

A UK nationwide study of people with type 1 diabetes admitted to hospital with COVID-19 infection.

AIMS/HYPOTHESIS: The aim of this work was to describe the clinical characteristics of adults with type 1 diabetes admitted to hospital and the risk factors associated with severe coronavirus disease-2019 (COVID-19) in the UK. METHODS: A retrospective cohort study was performed using data collected through a nationwide audit of people admitted to hospital with diabetes and COVID-19, conducted by the Association of British Clinical Diabetologists from March to October 2020. Prespecified demographic, clinical, medication and laboratory data were collected from the electronic and paper medical record systems of the participating hospitals by local clinicians. The primary outcome of the study, severe COVID-19, was defined as death in hospital and/or admission to the adult intensive care unit (AICU). Logistic regression models were used to generate age-adjusted ORs. RESULTS: Forty UK centres submitted data. The final dataset included 196 adults who were admitted to hospital and had both type 1 diabetes and COVID-19 on admission (male sex 55%, white 70%, with mean [SD] age 62 [19] years, BMI 28.3 [7.3] kg/m2 and last recorded HbA1c 76 [31] mmol/mol [9.1 (5.0)%]). The prevalence of pre-existing microvascular disease and macrovascular disease was 56% and 39%, respectively. The prevalence of diabetic ketoacidosis on admission was 29%. A total of 68 patients (35%) died or were admitted to AICU. The proportions of people that died were 7%, 38% and 38% of those aged <55, 55-74 and ≥75 years, respectively. BMI, serum creatinine levels and having one or more microvascular complications were positively associated with the primary outcome after adjusting for age. CONCLUSIONS/INTERPRETATION: In people with type 1 diabetes and COVID-19 who were admitted to hospital in the UK, higher BMI, poorer renal function and presence of microvascular complications were associated with greater risk of death and/or admission to AICU. Risk of severe COVID-19 is reassuringly very low in people with type 1 diabetes who are under 55 years of age without microvascular or macrovascular disease. IN PEOPLE WITH TYPE 1 DIABETES AND COVID-19 ADMITTED TO HOSPITAL IN THE UK, BMI AND ONE OR MORE MICROVASCULAR COMPLICATIONS HAD A POSITIVE ASSOCIATION AND LOW SERUM CREATINE LEVELS HAD A NEGATIVE ASSOCIATION WITH DEATH/ADMISSION TO INTENSIVE CARE UNIT AFTER ADJUSTING FOR AGE.

Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations on the use of sodium-glucose cotransporter inhibitors with insulin for treatment of type 1 diabetes (Updated October 2020).

Dapagliflozin (SGLT-2 inhibitor) and sotagliflozin (SGLT1/2 inhibitor) are two of the drugs of SGLT inhibitor class which have been recommended by the National Institute for Health and Care Excellence (NICE) in people with type 1 diabetes with BMI ≥27 kg/m2 . Dapagliflozin is licensed in the UK for use in the NHS while sotagliflozin may be available in future. These and possibly other SGLT inhibitors may be increasingly used in people with type 1 diabetes as new licences are obtained. These drugs have the potential to improve glycaemic control in people with type 1 diabetes with the added benefit of weight loss, better control of blood pressure and more time in optimal glucose range. However, SGLT inhibitors are associated with a higher incidence of diabetic ketoacidosis without significant hyperglycaemia. The present ABCD/Diabetes UK joint updated position statement is to guide people with type 1 diabetes and clinicians using these drugs help mitigate this risk and other potential complications. Particularly, caution needs to be exercised in people who are at risk of diabetic ketoacidosis due to low calorie diets, illnesses, injuries, starvation, excessive exercise, excessive alcohol consumption and reduced insulin administration among other precipitating factors for diabetic ketoacidosis.

Unusual Presentation of Case of a Lung Carcinoid Tumor With Ectopic Adrenocorticotropic Secretion (EAS) Associated With Acute Weight Gain and Peripheral Edema.

Ectopic adrenocorticotropic secretion (EAS) is classically related to small-cell lung cancer but is caused by a wide variety of tumors. In approximately one-fifth of cases, the cause remains unidentified. Excess adrenocorticotropic hormone (ACTH) leads to Cushing's syndrome, and the presentation can be due to biochemical derangements such as hypokalemia and hyperglycemia. Alternatively, it may manifest with secondary symptoms such as weight gain, hypertension, skin thinning, abdominal striae, and/or psychotic manifestations. The diagnosis is established through dynamic testing after confirming excess cortisol and ACTH levels. Imaging is then used to identify the hormonally active lesion. Controlling hypercortisolism with steroidogenesis inhibitors is the initial step before proceeding to definitive treatment. Ideally, tumor resection, if possible, but bilateral adrenalectomies are considered in cases not amenable to curative surgery.

Meeting the Challenge of Virtual Diabetes Care: A Consensus Viewpoint on the Positioning and Value of Oral Semaglutide in Routine Clinical Practice.

While glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, are among the most effective drugs for treating people with type 2 diabetes (T2D), they are clinically under-utilised. Until recently, the only route for semaglutide administration was via subcutaneous injection. However, an oral formulation of semaglutide was recently licensed, with the potential to address therapy inertia and increase patient adherence to treatment, which is essential in controlling blood glucose and reducing complications. The availability of oral semaglutide provides a new option for both clinicians and patients who are reluctant to use an injectable agent. This has been of particular importance in addressing the challenge of virtual diabetes care during the COVID-19 pandemic, circumventing the logistical problems that are often associated with subcutaneous medication administration. However, there remains limited awareness of the clinical and economic value of oral semaglutide in routine clinical practice. In this article, we present our consensus opinion on the role of oral semaglutide in routine clinical practice and discuss its value in reducing the burden of delivering diabetes care in the post-COVID-19 pandemic period of chronic disease management.

Defining the Role of SGLT2 Inhibitors in Primary Care: Time to Think Differently.

Disease burden in people with diabetes is mainly driven by long-term complications such as cardiovascular disease, heart failure and chronic kidney disease. This is a consequence of the interconnection between the cardiovascular, renal and metabolic systems, through a continuous chain of events referred to as 'the cardiorenal metabolic continuum'. Increasing evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial effects across all stages of the cardiorenal metabolic continuum, reducing morbidity and mortality in a wide range of individuals, from those with diabetes and multiple risk factors to those with established heart failure and chronic kidney disease, regardless of the presence of diabetes. Despite this robust evidence base, the complexity of label indications and misconceptions concerning potential side effects have resulted in a lack of clear understanding in primary care regarding the implementation of SGLT2is in clinical practice. With this in mind, we provide an overview of the clinical and economic benefits of SGLT2is across the cardiorenal metabolic continuum together with practical considerations in order to help address some of these concerns and clearly define the role of SGLT2is in primary care as a holistic outcomes-driven treatment with the potential to reduce disease burden across the cardiorenal metabolic spectrum.

A Narrative Review of Chronic Kidney Disease in Clinical Practice: Current Challenges and Future Perspectives.

Chronic kidney disease (CKD) is a complex disease which affects approximately 13% of the world's population. Over time, CKD can cause renal dysfunction and progression to end-stage kidney disease and cardiovascular disease. Complications associated with CKD may contribute to the acceleration of disease progression and the risk of cardiovascular-related morbidities. Early CKD is asymptomatic, and symptoms only present at later stages when complications of the disease arise, such as a decline in kidney function and the presence of other comorbidities associated with the disease. In advanced stages of the disease, when kidney function is significantly impaired, patients can only be treated with dialysis or a transplant. With limited treatment options available, an increasing prevalence of both the elderly population and comorbidities associated with the disease, the prevalence of CKD is set to rise. This review discusses the current challenges and the unmet patient need in CKD.

New Therapeutic Horizons in Chronic Kidney Disease: The Role of SGLT2 Inhibitors in Clinical Practice.

Chronic kidney disease (CKD) is a serious, progressive condition associated with significant patient morbidity. Hypertension control and use of renin-angiotensin system blockers are the cornerstones of treatment for CKD. However, even with these treatment strategies, many individuals will progress towards kidney failure. Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitor clinical trials with primary renal endpoints have firmly established SGLT2 inhibition, in addition to standard of care, as an effective strategy to slow down the progression of CKD and reduce some of its associated complications. The emergence of this new clinical evidence supports the use of SGLT2 inhibitors in the management of CKD in people with and without diabetes. As licensing and guidelines for SGLT2 inhibitors are updated, there is a need to adapt CKD treatment pathways and for this class of drugs to be included as part of standard care for CKD management. In this article, we have used consensus opinion alongside the available evidence to provide support for the healthcare community involved in CKD management, regarding the role of SGLT2 inhibitors in clinical practice. By highlighting appropriate prescribing and practical considerations, we aim to encourage greater and safe use of SGLT2 inhibitors for people with CKD, both with and without diabetes.

Blurring of vision with malaise.

We present the case of a 56-year-old female brought to the Emergency Department via routine ambulance transport with complaints of blurred vision and malaise. She was screened by ambulance crew using the facial arm speech time (FAST) tool and a basic top-to-toe assessment as per current routine. The examining practitioner performed a thorough assessment of the patient, revisiting the initial examination findings, and establishing new clinical features of visual field deficit and pan-systolic murmur. The likely diagnosis of septic emboli or stroke with infective endocarditis was identified through the power of rigorous history taking and examination. These were then supported by investigation with blood tests and imaging. This prompted discussion with a tertiary centre and subsequent transfer for further investigation and management. The patient's journey shows that there may indeed be a role for a more comprehensive (but not exhaustive) initial screening from ambulance services in order to help appropriately stream specific patients to hospital in a timelier manner (to meet the thrombolysis window). This case supports the addition of V (visual fields) to the FAST screening tool.

Optimising the Heart Failure Treatment Pathway: The Role of SGLT2 Inhibitors.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were first developed as glucose-lowering therapies for the treatment of diabetes. However, these drugs have now been recognised to prevent worsening heart-failure events, improve health-related quality of life, and reduce mortality in people with heart failure with reduced ejection fraction (HFrEF), including those both with and without diabetes. Despite robust clinical trial data demonstrating favourable outcomes with SGLT2 inhibitors for patients with HFrEF, there is a lack of familiarity with the HF indication for these drugs, which have been the remit of diabetologists to date. In this article we use consensus expert opinion alongside the available evidence and label indication to provide support for the healthcare community treating people with HF regarding positioning of SGLT2 inhibitors within the treatment pathway. By highlighting appropriate prescribing and practical considerations, we hope to encourage greater, and safe, use of SGLT2 inhibitors in this population.

Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations for non-diabetes specialists on the use of sodium glucose co-transporter 2 inhibitors in people with type 2 diabetes (January 2021).

Sodium glucose co-transporter 2 (SGLT2) inhibitors are now an established class of medications for the treatment of type 2 diabetes (T2D), no longer reserved for use by specialists in diabetes. They are being used increasingly for their cardiac and renal benefits by primary care, cardiology and renal teams for indications in parallel with diabetes care as part of holistic management. This guidance provides essential information on SGLT therapy, including the main advantages and the important risks of which healthcare professionals should be aware.

Risk Prediction of the Diabetes Missing Million: Identifying Individuals at High Risk of Diabetes and Related Complications.

Early diagnosis and effective management of type 2 diabetes (T2D) are crucial in reducing the risk of developing life-changing complications such as heart failure, stroke, kidney disease, blindness and amputation, which are also associated with significant costs for healthcare providers. However, as T2D symptoms often develop slowly it is not uncommon for people to live with T2D for years without being aware of their condition-commonly known as the undiagnosed missing million. By the time a diagnosis is received, many individuals will have already developed serious complications. While the existence of undiagnosed diabetes has long been recognised, wide-reaching awareness among the general public, clinicians and policymakers is lacking, and there is uncertainty in how best to identify high-risk individuals. In this article we have used consensus expert opinion alongside the available evidence, to provide support for the diabetes healthcare community regarding risk prediction of the missing million. Its purpose is to provide awareness of the risk factors for identifying individuals at high, moderate and low risk of T2D and T2D-related complications. The awareness of risk predictors, particularly in primary care, is important, so that appropriate steps can be taken to reduce the clinical and economic burden of T2D and its complications.

A Retrospective Observational Study: Is Absolute Lymphocyte Count a Prognostic Marker in COVID-19?

Aim Our study aimed to find a correlation between low absolute lymphocyte count and COVID-19-related mortality. Methods This study followed a retrospective observational cohort design to analyze the data of patients who presented with symptoms and signs of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at the Conquest Hospital and Eastbourne District General Hospital in East Sussex, United Kingdom, between February 10, 2020 and May 1, 2020, retrospectively. Survival and mortality for the first 30 days and comorbidities were analyzed for all patients who were tested for COVID-19 irrespective of swab results and had blood lymphocyte levels taken at the time of their visit to the ED and their data were analyzed for statistical significance. Results A total of 1226 patients had SARS-CoV-2 RNA identification swabs taken between February 10, 2020 and May 1, 2020. A cohort of 742 patients of these patients tested for COVID-19 also had blood lymphocyte levels measured. Overall, the lymphocyte count did not differ significantly between patients suspected to have COVID-19 infection with either positive or negative COVID-19 swab results. The lymphocyte count, however, was significantly lower in those who died from COVID-19 (p < 0.001) but when comorbidities were analyzed, we found an association between an increased number of comorbidities and a significantly decreased lymphocyte count. Conclusion Once adjusted for comorbidities, the lymphocyte count had no association with COVID-19 infection and mortality.

Correction to: Optimising the Benefits of SGLT2 Inhibitors for Type 1 Diabetes.

In the original article, Associated Medical Education Section has been published mistakenly. It has been removed from the original publication.

Optimising the Benefits of SGLT2 Inhibitors for Type 1 Diabetes.

Sodium-glucose cotransporter 2 (SGLT2) inhibitor clinical studies in type 1 diabetes mellitus (T1DM) have demonstrated reduced HbA1c and lower glucose variability with increased time in optimal glucose range as well as additional benefits of reductions in weight and insulin dose without increasing the incidence of hypoglycaemia. However, the appropriate use of SGLT2 inhibitor therapies within clinical practise to treat people with T1DM remains unclear. In this article we have used consensus expert opinion alongside the available evidence, product indication and most recent clinical guidance to provide support for the diabetes healthcare community regarding the appropriate use of SGLT2 inhibitors, focussing on specific considerations for appropriate prescribing of dapagliflozin within the T1DM management pathway. Its purpose is to provide awareness of the issues surrounding treatment with dapagliflozin in T1DM as well as offer practical guidance that also includes a checklist tool for appropriate dapagliflozin prescribing. The checklist aims to support clinicians in identifying those people with T1DM most likely to benefit from dapagliflozin treatment as well as situations where caution may be required.Funding: AstraZeneca UK Ltd.

Predicting the development of macrovascular disease in people with type 1 diabetes: A 9-year follow-up study.

The aim of the article was to use prospectively collected data on people with type 1 diabetes to assess which routinely collected clinical measures predict the development of macrovascular disease in people with type 1 diabetes. Data have been collected in a structured format at an annual review since 1985. For this study, all people with type 1 diabetes in the database in both 1992 and 2001 were ascertained. Data were extracted for a diagnosis of coronary artery disease, stroke, and peripheral vascular disease (macrovascular complications). Presence of other microvascular complications was also ascertained. Forty-one of 404 (10.1%) people had macrovascular disease at the index visit in 1992 and 61 others developed macrovascular complications during follow-up. People who developed macrovascular complications were older (48 +/- 12 versus 36 +/- 11 [SD] years; P = 0.000), had longer duration of diabetes (28 +/- 12 versus 18 +/- 11 years; P = 0.000), higher BMI (26.7 +/- 4.6 versus 25.4 +/- 3.6 kg/m2; P = 0.041), higher base line serum cholesterol (5.9 +/- 1.7 versus 5.2 +/- 1.1 mmol/L, P = 0.007), higher median base line triglyceride levels (1.5 [IQ range 0.9-2.6] versus 1.1 [0.8-1.7] mmol/L; P = 0.002), higher systolic BP (145 +/- 21 versus 129 +/- 20 mmHg; P = 0.000), and higher serum creatinine (102 +/- 57 versus 86 +/- 17 micromol/L; P = 0.038) than those who did not. We found no significant difference in the base line glycated hemoglobin in the two groups. The multivariate model showed that age, duration of diabetes, systolic BP, and serum cholesterol and creatinine levels predicted the development of macrovascular complications, which were also associated with the later development of microalbuminuria. Macrovascular complications developed in 16.8% of people with type 1 diabetes over a 9-year follow-up, and were predicted by potentially modifiable factors including higher BP, BMI, and serum triglyceride and cholesterol levels.

Hypoglycaemia in a patient who is non-diabetic.

A 59-year-old Caucasian man was seen in clinic following general practitioner's referral presenting with a 1-year history of hypoglycaemia. It was deemed important given his history that an insulinoma should be ruled out. The patient had an induced episode of hypoglycaemia while under medical supervision; C-peptide, insulin and insulin-like growth factor levels were measured. These results strongly suggested an insulinoma. He was subsequently referred to our local tertiary centre for surgical workup and excision of the insulinoma. This case reminds us that insulinoma, although rare, is an important differential to rule out in non-diabetic hypoglycaemia. Often the diagnosis is overlooked as their symptoms mimic many other conditions. Although there is no specific Driver and Vehicle Licensing Agency advice, we, as the healthcare provider, should be ensuring the patients inform them.