Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update.

BACKGROUND: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.

Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19.

BACKGROUND: We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals. METHODS AND RESULTS: One hundred and sixty-eight patients were evaluated 28-60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); p<0.01) and had lower 10-year cardiovascular risk (%) (8.1 (7.9) vs 15.0 (11.5); p<0.01) and Coronavirus Clinical Characterisation Consortium in-hospital mortality risk (7.3 (10.2) vs 12.7 (9.8); p<0.01). Healthcare worker status associated with less acute inflammation (peak C reactive protein 48 mg/L (IQR: 14-165) vs 112 mg/L (52-181)), milder illness reflected by WHO clinical severity score distribution (p=0.04) and shorter duration of admission (4 days (IQR: 2-6) vs 6 days (3-12)).In adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28-60 days postdischarge).After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934). CONCLUSION: Healthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome. TRIAL REGISTRATION NUMBER: NCT04403607.

Chronic pain and COVID-19 hospitalisation and mortality: a UK Biobank cohort study.

ABSTRACT: The risk of COVID-19 in those with chronic pain is unknown. We investigated whether self-reported chronic pain was associated with COVID-19 hospitalisation or mortality. UK Biobank recruited 502,624 participants aged 37 to 73 years between 2006 and 2010. Baseline exposure data, including chronic pain (>3 months, in at least 1 of 7 prespecified body sites) and chronic widespread pain (>3 months, all over body), were linked to COVID-19 hospitalisations or mortality. Univariable or multivariable Poisson regression analyses were performed on the association between chronic pain and COVID-19 hospitalisation and Cox regression analyses of the associations with COVID-19 mortality. Multivariable analyses adjusted incrementally for sociodemographic confounders, then lifestyle risk factors, and finally long-term condition count. Of 441,403 UK Biobank participants with complete data, 3180 (0.7%) were hospitalised for COVID-19 and 1040 (0.2%) died from COVID-19. Chronic pain was associated with hospital admission for COVID-19 even after adjustment for all covariates (incidence rate ratio 1.16; 95% confidence interval [CI] 1.08-1.24; P < 0.001), as was chronic widespread pain (incidence rate ratio 1.33; 95% CI 1.06-1.66; P = 0.012). There was clear evidence of a dose-response relationship with number of pain sites (fully adjusted global P-value < 0.001). After adjustment for all covariates, there was no association between chronic pain (HR 1.01; 95% CI 0.89-1.15; P = 0.834) but attenuated association with chronic widespread pain (HR 1.50, 95% CI 1.04-2.16, P-value = 0.032) and COVID-19 mortality. Chronic pain is associated with higher risk of hospitalisation for COVID-19, but the association with mortality is unclear. Future research is required to investigate these findings further and determine whether pain is associated with long COVID.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.

How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.

Comparative Incidence of Diabetes Following Hospital Admission for COVID-19 and Pneumonia: A Cohort Study.

OBJECTIVE: The incidence of diabetes may be elevated following coronavirus disease 2019 (COVID-19), but it is unclear whether this is specific to severe acute respiratory syndrome coronavirus 2 infection, associated with shared risk factors for severe COVID-19 and diabetes, and/or a generic risk following illness. RESEARCH DESIGN AND METHODS: People admitted to the hospital for COVID-19 and/or pneumonia between 1 April 2020 and 31 August 2020 in England were linked with the National Diabetes Audit to identify incident diabetes after discharge up to 31 March 2021. Comparator cohorts admitted with pneumonia over the same dates in 2017, 2018, and 2019 were followed until 31 March 2018, 31 March 2019, and 31 March 2020, respectively. Poisson regression models were used to calculate adjusted diabetes incidence rates. RESULTS: Using the cohort of people discharged from the hospital following a diagnosis of COVID-19 without pneumonia in 2020 as the standard population (incidence rate 16.4 [95% CI 12.8-20.7] per 1,000 person-years), adjusting for age, sex, ethnicity, and deprivation, gave incidence rates of 19.0 (95% CI 13.8-25.6) and 16.6 (95% CI 13.3-20.4) per 1,000 person-years for those admitted for COVID-19 with pneumonia and pneumonia without COVID-19, respectively, in 2020. These rates are not significantly different from those found after hospital admission for pneumonia in 2019, 2018, and 2017, at 13.7 (95% CI 10.8-17.3), 13.8 (95% CI 10.9-17.4), and 14.2 (95% CI 10.9-18.3) per 1,000 person-years, respectively. CONCLUSIONS: Our data do not support a clear impact of COVID-19 on the incidence of diabetes compared with risks in several comparator groups, including contemporaneously assessed risks in people hospitalized with pneumonia.

Ramadan fasting: recommendations for patients with cardiovascular disease.

Ramadan fasting is observed by most of the 1.8 billion Muslims around the world. It lasts for 1 month per the lunar calendar year and is the abstention from any food and drink from dawn to sunset. While recommendations on 'safe' fasting exist for patients with some chronic conditions, such as diabetes mellitus, guidance for patients with cardiovascular disease is lacking. We reviewed the literature to help healthcare professionals educate, discuss and manage patients with cardiovascular conditions, who are considering fasting. Studies on the safety of Ramadan fasting in patients with cardiac disease are sparse, observational, of small sample size and have short follow-up. Using expert consensus and a recognised framework, we risk stratified patients into 'low or moderate risk', for example, stable angina or non-severe heart failure; 'high risk', for example, poorly controlled arrhythmias or recent myocardial infarction; and 'very high risk', for example, advanced heart failure. The 'low-moderate risk' group may fast, provided their medications and clinical conditions allow. The 'high' or 'very high risk' groups should not fast and may consider safe alternatives such as non-consecutive fasts or fasting shorter days, for example, during winter. All patients who are fasting should be educated before Ramadan on their risk and management (including the risk of dehydration, fluid overload and terminating the fast if they become unwell) and reviewed after Ramadan to reassess their risk status and condition. Further studies to clarify the benefits and risks of fasting on the cardiovascular system in patients with different cardiovascular conditions should help refine these recommendations.

COVID-19 in people aged 18-64 in Sweden in the first year of the pandemic: Key factors for severe disease and death.

Background: Studies on risk factors for severe COVID-19 in people of working age have generally not included non-working persons or established population attributable fractions (PAFs) for occupational and other factors. Objectives: We describe the effect of job-related, sociodemographic, and other exposures on the incidence, relative risks and PAFs of severe COVID-19 in individuals aged 18-64. Methods: We conducted a registry-based study in Swedish citizens aged 18-64 from 1 January 2020 to 1 February 2021 with respect to COVID-19-related hospitalizations and death. Results: Of 6,205,459 persons, 272,043 (7.5%) were registered as infected, 3399 (0.05%) needed intensive care, and 620 (0.01%) died, with an estimated case fatality rate of 0.06% over the last 4-month period when testing was adequate. Non-Nordic origin was associated with a RR for need of intensive care of 3·32, 95%CI 2·19-3·36, and a PAF of 33·1% after adjustment for age, sex, work, region and comorbidities. In a second model with occupation as main exposure, and adjusted for age, sex, region, comorbidities and origin, essential workers had an RR of 1·51, 95%CI, 1·35-1·6, blue-collar workers 1·18, 95%CI 1·06-1·31, school staff 1·21, 95%CI 1·01-1·46, and health and social care workers 1·89, 95%CI 1·67-2·135) compared with people able to work from home, with altogether about 14% of the PAF associated with these occupations. Essential workers and blue-collar workers, but no other job categories had higher risk of death, adjusted RRs of 1·66, 95%CI 1·24-2·23 and 1·37, 95%CI 1·04-1·81, with adjusted PAFs of altogether 9%. Conclusion: Among people of working age in Sweden, overall mortality and case fatality were low. Occupations that require physical presence at work were associated with elevated risk of needing intensive care for COVID-19, with 14% cases attributable to this factor, and 9% of deaths.

Cohort profile: the Scottish Diabetes Research Network national diabetes cohort - a population-based cohort of people with diabetes in Scotland.

PURPOSE: The Scottish Diabetes Research Network (SDRN)-diabetes research platform was established to combine disparate electronic health record data into research-ready linked datasets for diabetes research in Scotland. The resultant cohort, 'The SDRN-National Diabetes Dataset (SDRN-NDS)', has many uses, for example, understanding healthcare burden and socioeconomic trends in disease incidence and prevalence, observational pharmacoepidemiology studies and building prediction tools to support clinical decision making. PARTICIPANTS: We estimate that >99% of those diagnosed with diabetes nationwide are captured into the research platform. Between 2006 and mid-2020, the cohort comprised 472 648 people alive with diabetes at any point in whom there were 4 million person-years of follow-up. Of the cohort, 88.1% had type 2 diabetes, 8.8% type 1 diabetes and 3.1% had other types (eg, secondary diabetes). Data are captured from all key clinical encounters for diabetes-related care, including diabetes clinic, primary care and podiatry and comprise clinical history and measurements with linkage to blood results, microbiology, prescribed and dispensed drug and devices, retinopathy screening, outpatient, day case and inpatient episodes, birth outcomes, cancer registry, renal registry and causes of death. FINDINGS TO DATE: There have been >50 publications using the SDRN-NDS. Examples of recent key findings include analysis of the incidence and relative risks for COVID-19 infection, drug safety of insulin glargine and SGLT2 inhibitors, life expectancy estimates, evaluation of the impact of flash monitors on glycaemic control and diabetic ketoacidosis and time trend analysis showing that diabetic ketoacidosis (DKA) remains a major cause of death under age 50 years. The findings have been used to guide national diabetes strategy and influence national and international guidelines. FUTURE PLANS: The comprehensive SDRN-NDS will continue to be used in future studies of diabetes epidemiology in the Scottish population. It will continue to be updated at least annually, with new data sources linked as they become available.

A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases.

OBJECTIVES: Informing an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively targeting interleukin-6 (IL-6) pathway in the context of immune-mediated inflammatory diseases. METHODS: A systematic literature research of all publications on IL-6 axis inhibition with bDMARDs published between January 2012 and December 2020 was performed using MEDLINE, EMBASE and Cochrane CENTRAL databases. Efficacy and safety outcomes were assessed in clinical trials including their long-term extensions and observational studies. Meeting abstracts from ACR, EULAR conferences and results on clinicaltrials.gov were taken into consideration. RESULTS: 187 articles fulfilled the inclusion criteria. Evidence for positive effect of IL-6 inhibition was available in various inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, cytokine release syndrome due to chimeric antigen receptor T cell therapy and systemic sclerosis-associated interstitial lung disease. Newcomers like satralizumab and anti-IL-6 ligand antibody siltuximab have expanded therapeutic approaches for Castleman's disease and neuromyelitis optica, respectively. IL-6 inhibition did not provide therapeutic benefits in psoriatic arthritis, ankylosing spondylitis and certain connective tissue diseases. In COVID-19, tocilizumab (TCZ) has proven to be therapeutic in advanced disease. Safety outcomes did not differ from other bDMARDs, except higher risks of diverticulitis and lower gastrointestinal perforations. Inconsistent results were observed in several studies investigating the risk for infections when comparing TCZ to TNF-inhibitors. CONCLUSION: IL-6 inhibition is effective for treatment of several inflammatory diseases with a safety profile that is widely comparable to other bDMARDs.

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records.

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK.

Associations between reductions in routine care delivery and non-COVID-19-related mortality in people with diabetes in England during the COVID-19 pandemic: a population-based parallel cohort study.

BACKGROUND: The Office for Health Improvement and Disparities, part of the UK Government Department of Health and Social Care, highlighted an emerging signal of increased non-COVID-19-related deaths in England between July and October, 2021, with a potentially disproportionate higher increase in people with diabetes. We aimed to substantiate and quantify this apparent excess mortality, and to investigate the association between diabetes routine care delivery and non-COVID-19-related-mortality in people with diabetes before and after the onset of the pandemic. METHODS: In this population-based parallel cohort study, we used the National Diabetes Audit (NDA) to identify people with diabetes in England. The primary outcome was non-COVID-19-related deaths between July 3, 2021, and Oct 15, 2021, in participants in the 2021 COVID-19 cohort (registered in the NDA in the periods Jan 1, 2019, to March 31, 2020, and Jan 1, 2020, to March 31, 2021) compared with deaths between June 29, 2019, and Oct 11, 2019 (the equivalent 15-week period in 2019) in the 2019 pre-COVID-19 comparator cohort (people registered in the NDA in the periods Jan 1, 2017, to March 31, 2018, and Jan 1, 2018 to March 31, 2019). In each cohort, multivariable logistic regression examined whether completion of eight diabetes care processes in each of the two years before the index mortality year was associated with non-COVID-19-related death, adjusting for diabetes type, age, sex, ethnicity, and socioeconomic deprivation. FINDINGS: There were 3 218 570 people in the 2021 cohort and 2 973 645 people in the 2019 comparator cohort. In the 2021 cohort, there were 30 118 non-COVID-19-related deaths in people with diabetes, compared with 27 132 in the comparator cohort, representing an 11% increase (95% CI 9-13). The unadjusted incidence rate ratio (IRR) for mortality in the 2021 cohort compared to the 2019 cohort was 1·026 (1·009-1·043; p=0·003), which was unchanged after adjustment for age, sex, ethnicity, socioeconomic deprivation, and diabetes type (IRR 1·023 (1·006-1·040); p=0·007). In the 2021 cohort, 853 660 (26·5%) people received all eight care processes in 2020-21 compared with 1 547 240 (48·1%) people in 2019-20; a 44·8% (95% CI 44·7-45·0) relative reduction. In the pre-COVID-19 comparator cohort, 1 370 315 (46·1%) people with diabetes received all eight care processes in 2018-19 compared with 1 437 740 (48·3%) in 2017-18; a 4·7% (95% CI 4·5-4·9) relative decrease. Non-COVID-19-related mortality in the 2021 cohort was highest in people who did not receive all eight care processes in either of the two previous years (OR 2·67 [95% CI 2·56-2·77]; p<0·001) compared with those who received all eight care processes in both previous years. Mortality was also significantly higher in those who received all eight care processes in 2019-20 but not in 2020-21 (OR 1·66 [95% CI 1·59-1·73]; p<0·001) or not in 2019-20 but in 2020-21 (OR 1·27 [1·20-1·35]; p<0·001). This pattern of association was similar in the 2019 pre-COVID-19 cohort. INTERPRETATION: Our results show an increased risk of mortality in those who did not receive all eight care processes in one or both of the previous two years. Our results provide evidence that the increased rate of non-COVID-19-related mortality in people with diabetes in England observed between July 3, and Oct 15 of 2021 is associated with a reduction in completion of routine diabetes care processes following the pandemic onset in 2020. FUNDING: None.

Severe COVID-19 in people 55 and older during the first year of the pandemic in Sweden.

BACKGROUND: Exposure to many contacts is the main risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while risk of serious disease and death is chiefly determined by old age and comorbidities. Relative and population-attributable fractions (PAFs) of multiple medical and social exposures for COVID-19 outcomes have not been evaluated among older adults. OBJECTIVES: We describe the effect of multiple exposures on the odds of testing positive for the virus and of severe disease (hospital care or death) and PAFs in Swedish citizens aged 55 years and above. METHODS: We used national registers to follow all citizens aged 55 years and above with respect to (1) testing positive, (2) hospitalization, and (3) death between 31 January 2020 and 1 February 2021. RESULTS: Of 3,410,241 persons, 156,017 (4.6%, mean age 68.3 years) tested positive for SARS-CoV-2, while 35,999 (1.1%, mean age 76.7 years) were hospitalized or died (12,384 deaths, 0.4%, mean age 84.0 years). Among the total cohort, the proportion living without home care or long-term care was 98.8% among persons aged 55-64 and 22.1% of those aged 95 and above. After multiple adjustment, home care and long-term care were associated with odds ratios of 7.9 (95% confidence interval [CI] 6.8-9.1) and 22.5 (95% CI 19.6-25.7) for mortality, with PAFs of 21.9% (95% CI 20.9-22.9) and 33.3% (95% CI 32.4-34.3), respectively. CONCLUSION: Among Swedish residents aged 55 years and above, those with home care or long-term care had markedly increased risk for COVID-19 death during the first year of the pandemic, with over 50% of deaths attributable to these factors.

A multisystem, cardio-renal investigation of post-COVID-19 illness.

The pathophysiology and trajectory of post-Coronavirus Disease 2019 (COVID-19) syndrome is uncertain. To clarify multisystem involvement, we undertook a prospective cohort study including patients who had been hospitalized with COVID-19 (ClinicalTrials.gov ID NCT04403607 ). Serial blood biomarkers, digital electrocardiography and patient-reported outcome measures were obtained in-hospital and at 28-60 days post-discharge when multisystem imaging using chest computed tomography with pulmonary and coronary angiography and cardio-renal magnetic resonance imaging was also obtained. Longer-term clinical outcomes were assessed using electronic health records. Compared to controls (n = 29), at 28-60 days post-discharge, people with COVID-19 (n = 159; mean age, 55 years; 43% female) had persisting evidence of cardio-renal involvement and hemostasis pathway activation. The adjudicated likelihood of myocarditis was 'very likely' in 21 (13%) patients, 'probable' in 65 (41%) patients, 'unlikely' in 56 (35%) patients and 'not present' in 17 (11%) patients. At 28-60 days post-discharge, COVID-19 was associated with worse health-related quality of life (EQ-5D-5L score 0.77 (0.23) versus 0.87 (0.20)), anxiety and depression (PHQ-4 total score 3.59 (3.71) versus 1.28 (2.67)) and aerobic exercise capacity reflected by predicted maximal oxygen utilization (20.0 (7.6) versus 29.5 (8.0) ml/kg/min) (all P < 0.01). During follow-up (mean, 450 days), 24 (15%) patients and two (7%) controls died or were rehospitalized, and 108 (68%) patients and seven (26%) controls received outpatient secondary care (P = 0.017). The illness trajectory of patients after hospitalization with COVID-19 includes persisting multisystem abnormalities and health impairments that could lead to substantial demand on healthcare services in the future.

Managing weight and glycaemic targets in people with type 2 diabetes—How far have we come?

IntroductionAs the vast majority of people with type 2 diabetes (T2D) are also overweight or obese, healthcare professionals (HCP) are faced with the task of addressing both weight management and glucose control. In this narrative review, we aim to identify the challenges of reaching and maintaining body weight targets in people with T2D and highlight current and future treatment interventions.MethodsA search of the PubMed database was conducted using the search terms “diabetes” and “weight loss.”ResultsAccording to emerging evidence, treating obesity may be antecedent to the development and progression of T2D. While clinical benefits typically set in upon achieving a weight loss of 3–5%, these benefits are progressive leading to further health improvements, and weight loss of >15% can have a disease‐modifying effect in people with T2D, an outcome that up to recently could not be achieved with any blood glucose‐lowering pharmacotherapy. However, advanced treatment options with weight‐loss effects currently in development including the dual GIP/GLP‐1 receptor agonists may enable simultaneous achievement of individual glycemic and weight goals.ConclusionDespite considerable therapeutic progress, there is still a large unmet medical need in patients with T2D who miss their individualized glycemic and weight‐loss targets. Nonetheless, it is to be expected that development of future therapies and their use will favourably change the scenario of weight and glucose control in T2D.

The association between a lifestyle score, socioeconomic status, and COVID-19 outcomes within the UK Biobank cohort.

BACKGROUND: Infection with SARS-CoV-2 virus (COVID-19) impacts disadvantaged groups most. Lifestyle factors are also associated with adverse COVID-19 outcomes. To inform COVID-19 policy and interventions, we explored effect modification of socioeconomic-status (SES) on associations between lifestyle and COVID-19 outcomes. METHODS: Using data from UK-Biobank, a large prospective cohort of 502,536 participants aged 37-73 years recruited between 2006 and 2010, we assigned participants a lifestyle score comprising nine factors. Poisson regression models with penalised splines were used to analyse associations between lifestyle score, deprivation (Townsend), and COVID-19 mortality and severe COVID-19. Associations between each exposure and outcome were examined independently before participants were dichotomised by deprivation to examine exposures jointly. Models were adjusted for sociodemographic/health factors. RESULTS: Of 343,850 participants (mean age > 60 years) with complete data, 707 (0.21%) died from COVID-19 and 2506 (0.76%) had severe COVID-19. There was evidence of a nonlinear association between lifestyle score and COVID-19 mortality but limited evidence for nonlinearity between lifestyle score and severe COVID-19 and between deprivation and COVID-19 outcomes. Compared with low deprivation, participants in the high deprivation group had higher risk of COVID-19 outcomes across the lifestyle score. There was evidence for an additive interaction between lifestyle score and deprivation. Compared with participants with the healthiest lifestyle score in the low deprivation group, COVID-19 mortality risk ratios (95% CIs) for those with less healthy scores in low versus high deprivation groups were 5.09 (1.39-25.20) and 9.60 (4.70-21.44), respectively. Equivalent figures for severe COVID-19 were 5.17 (2.46-12.01) and 6.02 (4.72-7.71). Alternative SES measures produced similar results. CONCLUSIONS: Unhealthy lifestyles are associated with higher risk of adverse COVID-19, but risks are highest in the most disadvantaged, suggesting an additive influence between SES and lifestyle. COVID-19 policy and interventions should consider both lifestyle and SES. The greatest public health benefit from lifestyle focussed COVID-19 policy and interventions is likely to be seen when greatest support for healthy living is provided to the most disadvantaged groups.

Epidemiology of type 2 diabetes remission in Scotland in 2019: A cross-sectional population-based study.

BACKGROUND: Clinical pathways are changing to incorporate support and appropriate follow-up for people to achieve remission of type 2 diabetes, but there is limited understanding of the prevalence of remission in current practice or patient characteristics associated with remission. METHODS AND FINDINGS: We carried out a cross-sectional study estimating the prevalence of remission of type 2 diabetes in all adults in Scotland aged ≥30 years diagnosed with type 2 diabetes and alive on December 31, 2019. Remission of type 2 diabetes was assessed between January 1, 2019 and December 31, 2019. We defined remission as all HbA1c values <48 mmol/mol in the absence of glucose-lowering therapy (GLT) for a continuous duration of ≥365 days before the date of the last recorded HbA1c in 2019. Multivariable logistic regression in complete and multiply imputed datasets was used to examine characteristics associated with remission. Our cohort consisted of 162,316 individuals, all of whom had at least 1 HbA1c ≥48 mmol/mol (6.5%) at or after diagnosis of diabetes and at least 1 HbA1c recorded in 2019 (78.5% of the eligible population). Over half (56%) of our cohort was aged 65 years or over in 2019, and 64% had had type 2 diabetes for at least 6 years. Our cohort was predominantly of white ethnicity (74%), and ethnicity data were missing for 19% of the cohort. Median body mass index (BMI) at diagnosis was 32.3 kg/m2. A total of 7,710 people (4.8% [95% confidence interval [CI] 4.7 to 4.9]) were in remission of type 2 diabetes. Factors associated with remission were older age (odds ratio [OR] 1.48 [95% CI 1.34 to 1.62] P < 0.001) for people aged ≥75 years compared to 45 to 54 year group), HbA1c <48 mmol/mol at diagnosis (OR 1.31 [95% CI 1.24 to 1.39] P < 0.001) compared to 48 to 52 mmol/mol), no previous history of GLT (OR 14.6 [95% CI 13.7 to 15.5] P < 0.001), weight loss from diagnosis to 2019 (OR 4.45 [95% CI 3.89 to 5.10] P < 0.001) for ≥15 kg of weight loss compared to 0 to 4.9 kg weight gain), and previous bariatric surgery (OR 11.9 [95% CI 9.41 to 15.1] P < 0.001). Limitations of the study include the use of a limited subset of possible definitions of remission of type 2 diabetes, missing data, and inability to identify self-funded bariatric surgery. CONCLUSIONS: In this study, we found that 4.8% of people with type 2 diabetes who had at least 1 HbA1c ≥48 mmol/mol (6.5%) after diagnosis of diabetes and had at least 1 HbA1c recorded in 2019 had evidence of type 2 diabetes remission. Guidelines are required for management and follow-up of this group and may differ depending on whether weight loss and remission of diabetes were intentional or unintentional. Our findings can be used to evaluate the impact of future initiatives on the prevalence of type 2 diabetes remission.

Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England.

BACKGROUND: In patients with type 2 diabetes, hyperglycaemia is an independent risk factor for COVID-19-related mortality. Associations between pre-infection prescription for glucose-lowering drugs and COVID-19-related mortality in people with type 2 diabetes have been postulated but only investigated in small studies and limited to a few agents. We investigated whether there are associations between prescription of different classes of glucose-lowering drugs and risk of COVID-19-related mortality in people with type 2 diabetes. METHODS: This was a nationwide observational cohort study done with data from the National Diabetes Audit for people with type 2 diabetes and registered with a general practice in England since 2003. Cox regression was used to estimate the hazard ratio (HR) of COVID-19-related mortality in people prescribed each class of glucose-lowering drug, with covariate adjustment with a propensity score to address confounding by demographic, socioeconomic, and clinical factors. FINDINGS: Among the 2 851 465 people with type 2 diabetes included in our analyses, 13 479 (0·5%) COVID-19-related deaths occurred during the study period (Feb 16 to Aug 31, 2020), corresponding to a rate of 8·9 per 1000 person-years (95% CI 8·7-9·0). The adjusted HR associated with recorded versus no recorded prescription was 0·77 (95% CI 0·73-0·81) for metformin and 1·42 (1·35-1·49) for insulin. Adjusted HRs for prescription of other individual classes of glucose-lowering treatment were as follows: 0·75 (0·48-1·17) for meglitinides, 0·82 (0·74-0·91) for SGLT2 inhibitors, 0·94 (0·82-1·07) for thiazolidinediones, 0·94 (0·89-0·99) for sulfonylureas, 0·94 (0·83-1·07) for GLP-1 receptor agonists, 1·07 (1·01-1·13) for DPP-4 inhibitors, and 1·26 (0·76-2·09) for α-glucosidase inhibitors. INTERPRETATION: Our results provide evidence of associations between prescription of some glucose-lowering drugs and COVID-19-related mortality, although the differences in risk are small and these findings are likely to be due to confounding by indication, in view of the use of different drug classes at different stages of type 2 diabetes disease progression. In the context of the COVID-19 pandemic, there is no clear indication to change prescribing of glucose-lowering drugs in people with type 2 diabetes. FUNDING: None.

Thromboembolic Risk in Hospitalized and Nonhospitalized COVID-19 Patients: A Self-Controlled Case Series Analysis of a Nationwide Cohort.

OBJECTIVE: To assess the associations between coronavirus disease 2019 (COVID-19) infection and thromboembolism including myocardial infarction (MI), ischemic stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE). PATIENTS AND METHODS: A self-controlled case-series study was conducted covering the whole of Scotland's general population. The study population comprised individuals with confirmed (positive test) COVID-19 and at least one thromboembolic event between March 2018 and October 2020. Their incidence rates during the risk interval (5 days before to 56 days after the positive test) and the control interval (the remaining periods) were compared intrapersonally. RESULTS: Across Scotland, 1449 individuals tested positive for COVID-19 and experienced a thromboembolic event. The risk of thromboembolism was significantly elevated over the whole risk period but highest in the 7 days following the positive test (incidence rate ratio, 12.01; 95% CI, 9.91 to 14.56) in all included individuals. The association was also present in individuals not originally hospitalized for COVID-19 (incidence rate ratio, 4.07; 95% CI, 2.83 to 5.85). Risk of MI, stroke, PE, and DVT were all significantly higher in the week following a positive test. The risk of PE and DVT was particularly high and remained significantly elevated even 56 days following the test. CONCLUSION: Confirmed COVID-19 infection was associated with early elevations in risk with MI, ischemic stroke, and substantially stronger and prolonged elevations with DVT and PE both in hospital and community settings. Clinicians should consider thromboembolism, especially PE, among people with COVID-19 in the community.

Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study using UK Biobank.

BACKGROUND: Understanding of the role of ethnicity and socioeconomic position in the risk of developing SARS-CoV-2 infection is limited. We investigated this in the UK Biobank study. METHODS: The UK Biobank study recruited 40-70-year-olds in 2006-2010 from the general population, collecting information about self-defined ethnicity and socioeconomic variables (including area-level socioeconomic deprivation and educational attainment). SARS-CoV-2 test results from Public Health England were linked to baseline UK Biobank data. Poisson regression with robust standard errors was used to assess risk ratios (RRs) between the exposures and dichotomous variables for being tested, having a positive test and testing positive in hospital. We also investigated whether ethnicity and socioeconomic position were associated with having a positive test amongst those tested. We adjusted for covariates including age, sex, social variables (including healthcare work and household size), behavioural risk factors and baseline health. RESULTS: Amongst 392,116 participants in England, 2658 had been tested for SARS-CoV-2 and 948 tested positive (726 in hospital) between 16 March and 3 May 2020. Black and south Asian groups were more likely to test positive (RR 3.35 (95% CI 2.48-4.53) and RR 2.42 (95% CI 1.75-3.36) respectively), with Pakistani ethnicity at highest risk within the south Asian group (RR 3.24 (95% CI 1.73-6.07)). These ethnic groups were more likely to be hospital cases compared to the white British. Adjustment for baseline health and behavioural risk factors led to little change, with only modest attenuation when accounting for socioeconomic variables. Socioeconomic deprivation and having no qualifications were consistently associated with a higher risk of confirmed infection (RR 2.19 for most deprived quartile vs least (95% CI 1.80-2.66) and RR 2.00 for no qualifications vs degree (95% CI 1.66-2.42)). CONCLUSIONS: Some minority ethnic groups have a higher risk of confirmed SARS-CoV-2 infection in the UK Biobank study, which was not accounted for by differences in socioeconomic conditions, baseline self-reported health or behavioural risk factors. An urgent response to addressing these elevated risks is required.

Obesity as a Risk Factor for Severe COVID-19: Summary of the Best Evidence and Implications for Health Care.

PURPOSE OF REVIEW: To collate the best evidence from several strands-epidemiological, genetic, comparison with historical data and mechanistic information-and ask whether obesity is an important causal and potentially modifiable risk factor for severe COVID-19 outcomes. RECENT FINDINGS: Several hundred studies provide powerful evidence that body mass index (BMI) is a strong linear risk factor for severe COVID-19 outcomes, with recent studies suggesting ~5-10% higher risk for COVID-19 hospitalisation per every kg/m2 higher BMI. Genetic data concur with hazard ratios increasing by 14% per every kg/m2 higher BMI. BMI to COVID-19 links differ markedly from prior BMI-infection associations and are further supported as likely causal by multiple biologically plausible pathways. Excess adiposity appears to be an important, modifiable risk factor for adverse COVID-19 outcomes across all ethnicities. The pandemic is also worsening obesity levels. It is imperative that medical systems worldwide meet this challenge by upscaling investments in obesity prevention and treatments.