Analysis of continuous glucose tracking data in people with type 1 diabetes after COVID-19 vaccination reveals unexpected link between immune and metabolic response, augmented by adjunctive oral medication.

INTRODUCTION: The COVID-19 vaccination programme is under way worldwide. Anecdotal evidence is increasing that some people with type 1 diabetes mellitus (T1DM) experience temporary instability of blood glucose (BG) levels post-vaccination which normally settles within 2-3 days. We report an analysis of BG profiles of 20 individuals before/after vaccination. METHODS: We examined the BG profile of 20 consecutive adults (18 years of age or more) with T1DM using the FreeStyle Libre flash glucose monitor in the period immediately before and after COVID-19 vaccination. The primary outcome measure was percentage (%) BG readings in the designated target range 3.9-10 mmmol/L as reported on the LibreView portal for 7 days prior to the vaccination (week -1) and the 7 days after the vaccination (week +1). RESULTS: There was a significant decrease in the %BG on target following the COVID-vaccination for the 7 days following vaccination (mean 45.2% ± SE 4.2%) vs pre-COVID-19 vaccination (mean 52.6% ± SE 4.5%). This was mirrored by an increase in the proportion of readings in other BG categories 10.1%-13.9%/≥14%. There was no significant change in BG variability in the 7days post-COVID-19 vaccination. This change in BG proportion on target in the week following vaccination was most pronounced for people taking Metformin/Dapagliflozin+basal-bolus insulin (-23%) vs no oral hypoglycaemic agents (-4%), and median age <53 vs ≥53 years (greater reduction in %BG in target for older individuals (-18% vs -9%)). CONCLUSION: In T1DM, we have shown that COVID-19 vaccination can cause temporary perturbation of BG, with this effect more pronounced in patients talking oral hypoglycaemic medication plus insulin, and in older individuals. This may also have consequences for patients with T2DM who are currently not supported by flash glucose monitoring.

Incidence and outcomes of long QTc in acute medical admissions.

AIMS: Prolonged QT interval on electrocardiogram (ECG) increases the risk of ventricular arrhythmia. Patients admitted to acute medical units (AMU) may be at risk of QT prolongation from multiple, recognised risk factors. Few data exist regarding incidence or outcomes of QT prolongation in acute general medical admissions. The aims were to determine the incidence of Bazett's-corrected QT (QTc) prolongation upon admission to AMU; the relationship between QTc and inpatient mortality, length of stay and readmission; proportion with prolonged QTc subsequently administered QT interval-prolonging drugs. METHODS: Retrospective, observational study of 1000 consecutive patients admitted to an AMU in a large urban hospital. EXCLUSION CRITERIA: age <18 years, ventricular pacing, poor quality/absent ECG. QTc determined manually from ECG obtained within 4-hours of admission. QTc prolongation considered ≥470 milliseconds (males) and ≥480 milliseconds (females). In both genders, >500 milliseconds was considered severe. Study end-points, (a) incidence of QTc prolongation at admission; (b) inpatient mortality, length of stay and readmission rates; (c) proportion with QTc prolongation subsequently administered QT interval-prolonging drugs. RESULTS: Of 1000 patients, 288 patients were excluded, therefore final sample was n = 712. Patient age (mean ± SD) was 63.1 ± 19.4 years; females 49%. QTc prolongation was present in n = 50 (7%) at admission; 1.7% had QTc interval >500 ms. Of the 50 patients admitted with prolonged QTc, 6 (12%) were subsequently administered QT interval-prolonging drugs. QTc prolongation was not associated with worse inpatient mortality or readmission rate. Length of stay was greater in those with prolonged QTc, 7.2 (IQR 2.4-13.2) days vs 3.3 (IQR 1.3-10.0; P = 0.004), however, in a regression model, presence of QTc did not independently affect length of stay. CONCLUSIONS: QTc interval prolongation is frequent among patients admitted to AMU. QT interval-prolonging drugs are commonly prescribed to patients presenting with prolonged QTc but whether this affects clinical outcomes is uncertain.

The normal range: it is not normal and it is not a range.

The NHS 'Choose Wisely' campaign places greater emphasis on the clinician-patient dialogue. Patients are often in receipt of their laboratory data and want to know whether they are normal. But what is meant by normal? Comparator data, to a measured value, are colloquially known as the 'normal range'. It is often assumed that a result outside this limit signals disease and a result within health. However, this range is correctly termed the 'reference interval'. The clinical risk from a measured value is continuous, not binary. The reference interval provides a point of reference against which to interpret an individual's results-rather than defining normality itself. This article discusses the theory of normality-and describes that it is relative and situational. The concept of normality being not an absolute state influenced the development of the reference interval. We conclude with suggestions to optimise the use and interpretation of the reference interval, thereby facilitating greater patient understanding.

Systematic review of preoperative n-3 fatty acids in major gastrointestinal surgery.

Objectives: Perioperative nutrition aims to replenish nutritional stores before surgery and reduce postoperative complications. 'Immunonutrition' (including omega-3 fatty acids) may modulate the immune system and attenuate the postoperative inflammatory response. Hitherto, immunonutrition has overwhelmingly been administered in the postoperative period-however, this may be too late to provide benefit. Design: A systematic literature search using MEDLINE and EMBASE for randomized controlled trials (RCTs). Setting: Perioperative major gastrointestinal surgery. Participants: Patients undergoing major gastrointestinal surgery. Interventions: Omega-3 fatty acid supplementation commenced in the preoperative period, with or without continuation into postoperative period. Main outcome measures: The effect of preoperative omega-3 fatty acids on inflammatory response and clinical outcomes. Results: 833 studies were identified. After applying inclusion and exclusion criteria, 12 RCTs, involving 1456 randomized patients, were included. Ten articles exclusively enrolled patients with cancer. Seven studies used a combination of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) as the intervention and five studies used EPA alone. Eight out of 12 studies continued preoperative nutritional support into the postoperative period.Of the nine studies reporting mortality, no difference was seen. Duration of hospitalisation ranged from 4.5 to 18 days with intervention and 3.5 to 23.5 days with control. Omega-3 fatty acids had no effect on postoperative C-reactive protein and the effect on cytokines (including tumor necrosis factor-α, interleukin (IL)-6 and IL-10) was inconsistent. Ten of the 12 studies had low risk of bias, with one study having moderate bias from allocation and blinding. Conclusions: There is insufficient evidence to support routine preoperative omega-3 fatty acid supplementation for major gastrointestinal surgery, even when this is continued after surgery. PROSPERO registration number: CRD42018108333.

Eicosapentaenoic acid-rich oil supplementation activates PPAR-γ and delays skin wound healing in type 1 diabetic mice.

Delayed wound healing is a devastating complication of diabetes and supplementation with fish oil, a source of anti-inflammatory omega-3 (ω-3) fatty acids including eicosapentaenoic acid (EPA), seems an appealing treatment strategy. However, some studies have shown that ω-3 fatty acids may have a deleterious effect on skin repair and the effects of oral administration of EPA on wound healing in diabetes are unclear. We used streptozotocin-induced diabetes as a mouse model to investigate the effects of oral administration of an EPA-rich oil on wound closure and quality of new tissue formed. Gas chromatography analysis of serum and skin showed that EPA-rich oil increased the incorporation of ω-3 and decreased ω-6 fatty acids, resulting in reduction of the ω-6/ω-3 ratio. On the tenth day after wounding, EPA increased production of IL-10 by neutrophils in the wound, reduced collagen deposition, and ultimately delayed wound closure and impaired quality of the healed tissue. This effect was PPAR-γ-dependent. EPA and IL-10 reduced collagen production by fibroblasts in vitro. In vivo, topical PPAR-γ-blockade reversed the deleterious effects of EPA on wound closure and on collagen organization in diabetic mice. We also observed a reduction in IL-10 production by neutrophils in diabetic mice treated topically with the PPAR-γ blocker. These results show that oral supplementation with EPA-rich oil impairs skin wound healing in diabetes, acting on inflammatory and non-inflammatory cells.

Improved diabetes control, allowing insulin cessation, after direct acting antiviral treatment (DAAT) of hepatitis C.

There is a bidirectional relationship between hepatitis C and type 2 diabetes. The risk for developing type 2 diabetes is increased in patients with chronic hepatitis C virus (HCV) infection-with the prevalence of diabetes ranging from 13% to 33%. This is likely underpinned by insulin resistance. Type 2 diabetes may also be a predisposing factor for HCV infection. The new non-interferon-based therapeutic regimens for hepatitis C have transformed care and can eradicate disease. In this report, we show how such a regimen eradicated viral load, improved hepatocellular blood markers and significantly improved dysglycaemia, such that all glucose-lowering medication could be stopped.

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

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.

Schistosomiasis and associated iron-deficiency anaemia presenting decades after immigration from sub-Saharan Africa.

Chronic schistosomiasis and its intestinal manifestations can lead to anaemia. However, schistosomiasis resulting in anaemia is rare in the UK. This report aims to raise awareness of schistosomiasis in immigrants to the UK and prevent missed diagnosis.

Silent diabetes mellitus, periodontitis and a new case of thalamic abscess.

Brain abscess is an unusual complication of uncontrolled diabetes. A solitary thalamic abscess is an uncommon type of brain abscess. We report a case of thalamic abscess, whereupon diabetes mellitus and periodontitis were diagnosed. The diagnosis and management of thalamic abscess, and the interplay of type 2 diabetes and periodontitis are discussed. A 56-year-old, Caucasian, man with no medical or travel history, presented with 5-day symptoms of meningeal irritation. Body mass index 30.6 kg/m(2). CT demonstrated a solitary midline lesion with neoplasia as a differential diagnosis. It was biopsied and cultures grew Streptococcus milleri. He was treated by stereotactic puncture, external drainage and targeted intrathecal and systemic antibiotic therapy. HIV negative but glycated haemoglobin (HbA1c) 10.7% (93 mmol/mol). Dental examination revealed a small molar abscess. Radiological resolution of the thalamic abscess occurred within 2 months. Diabetes improved with 7 weeks of insulin, and maintained on metformin, HbA1c 6.9% (51 mmol/mol). There was no residual neurological disability.