Publications by authors named "Kamlesh Khunti"

615 Publications

Indirect impact of the COVID-19 pandemic on hospitalisations for cardiometabolic conditions and their management: A systematic review.

Prim Care Diabetes 2021 May 28. Epub 2021 May 28.

Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, UK.

Background: The Coronavirus disease 2019 (COVID-19) pandemic has led to a dramatic crisis in health care systems worldwide. These may have significant implications for the management of cardiometabolic diseases. We conducted a systematic review of published evidence to assess the indirect impact of the COVID-19 pandemic on hospitalisations for cardiovascular diseases and their management.

Methods: Studies that evaluated volume of hospitalisations for cardiometabolic conditions and their management with comparisons between the COVID-19 and pre-COVID periods were identified from MEDLINE, Embase and the reference list of relevant studies from January 2020 to 25 February 2021.

Results: We identified 103 observational studies, with most studies assessing hospitalisations for acute cardiovascular conditions such as acute coronary syndrome, ischemic strokes and heart failure. About 89% of studies reported a decline in hospitalisations during the pandemic compared to pre-pandemic times, with reductions ranging from 20.2 to 73%. Severe presentation, less utilization of cardiovascular procedures, and longer patient- and healthcare-related delays were common during the pandemic. Most studies reported shorter length of hospital stay during the pandemic than before the pandemic (1-8 vs 2-12 days) or no difference in length of stay. Most studies reported no change in in-hospital mortality among hospitalised patients.

Conclusion: Clinical care of patients for acute cardiovascular conditions, their management and outcomes have been adversely impacted by the COVID-19 pandemic. Patients should be educated via population-wide approaches on the need for timely medical contact and health systems should put strategies in place to provide timely care to patients at high risk.

Systematic Review Registration: PROSPERO 2021: CRD42021236102.
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http://dx.doi.org/10.1016/j.pcd.2021.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162904PMC
May 2021

Promoting physical activity in a multi-ethnic population at high risk of diabetes: the 48-month PROPELS randomised controlled trial.

BMC Med 2021 Jun 3;19(1):130. Epub 2021 Jun 3.

Diabetes Research Centre, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK.

Background: Physical activity is associated with a reduced risk of type 2 diabetes and cardiovascular disease but limited evidence exists for the sustained promotion of increased physical activity within diabetes prevention trials. The aim of the study was to investigate the long-term effectiveness of the Walking Away programme, an established group-based behavioural physical activity intervention with pedometer use, when delivered alone or with a supporting mHealth intervention.

Methods: Those at risk of diabetes (nondiabetic hyperglycaemia) were recruited from primary care, 2013-2015, and randomised to (1) Control (information leaflet); (2) Walking Away (WA), a structured group education session followed by annual group-based support; or (3) Walking Away Plus (WAP), comprising WA annual group-based support and an mHealth intervention delivering tailored text messages supported by telephone calls. Follow-up was conducted at 12 and 48 months. The primary outcome was accelerometer measured ambulatory activity (steps/day). Change in primary outcome was analysed using analysis of covariance with adjustment for baseline, randomisation and stratification variables.

Results: One thousand three hundred sixty-six individuals were randomised (median age = 61 years, ambulatory activity = 6638 steps/day, women = 49%, ethnic minorities = 28%). Accelerometer data were available for 1017 (74%) individuals at 12 months and 993 (73%) at 48 months. At 12 months, WAP increased their ambulatory activity by 547 (97.5% CI 211, 882) steps/day compared to control and were 1.61 (97.5% CI 1.05, 2.45) times more likely to achieve 150 min/week of moderate-to-vigorous physical activity. Differences were not maintained at 48 months. WA was no different to control at 12 or 48 months. Secondary anthropometric and health outcomes were largely unaltered in both intervention groups apart from small reductions in body weight in WA (~ 1 kg) at 12- and 48-month follow-up.

Conclusions: Combining a pragmatic group-based intervention with text messaging and telephone support resulted in modest changes to physical activity at 12 months, but changes were not maintained at 48 months.

Trial Registration: ISRCTN 83465245 (registered on 14 June 2012).
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http://dx.doi.org/10.1186/s12916-021-01997-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173914PMC
June 2021

Chronic Kidney Disease in Diabetes: Guidelines from KDIGO.

Am Fam Physician 2021 Jun;103(11):698-700

Steno Diabetes Center, University of Copenhagen, Copenhagen, Denmark.

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June 2021

The effects of a leaflet-based intervention, 'Hypos can strike twice', on recurrent hypoglycaemic attendances by ambulance services: A non-randomised stepped wedge study.

Diabet Med 2021 May 30:e14612. Epub 2021 May 30.

Community and Health Research Unit and Lincoln Clinical Trials Unit, School of Health and Social Care, University of Lincoln, Lincoln, UK.

Aims: We aimed to investigate the effect of an intervention in which ambulance personnel provided advice supported by a booklet-'Hypos can strike twice'-issued following a hypoglycaemic event to prevent future ambulance attendances.

Methods: We used a non-randomised stepped wedge-controlled design. The intervention was introduced at different times (steps) in different areas (clusters) of operation within East Midlands Ambulance Service NHS Trust (EMAS). During the first step (T0), no clusters were exposed to the intervention, and during the last step (T3), all clusters were exposed. Data were analysed using a general linear mixed model (GLMM) and an interrupted-time series analysis (ITSA).

Results: The study included 4825 patients (mean age 65.42 years, SD 19.42; 2,166 females) experiencing hypoglycaemic events attended by EMAS. GLMM indicated a reduction in the number of unsuccessful attendances (i.e., attendance followed by a repeat attendance) in the final step of the intervention when compared to the first (odds ratio OR: 0.50, 95%CI: 0.33-0.76, p = 0.001). ITSA indicated a significant decrease in repeat ambulance attendances for hypoglycaemia-relative to the pre-intervention trend (p = 0.008). Furthermore, the hypoglycaemia care bundle was delivered in 66% of attendances during the intervention period, demonstrating a significant level of practice change (p < 0.001).

Conclusion: The 'Hypos can strike twice' intervention had a positive effect on reducing numbers of repeat attendances for hypoglycaemia and in achieving the care bundle. The study supports the use of information booklets by ambulance clinicians to prevent future attendances for recurrent hypoglycaemic events.
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http://dx.doi.org/10.1111/dme.14612DOI Listing
May 2021

Should vaccination for healthcare workers be mandatory?

J R Soc Med 2021 05;114(5):235-236

School of Medicine, University of Nottingham, NG7 2TU, UK.

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http://dx.doi.org/10.1177/01410768211013525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150569PMC
May 2021

Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries.

BMJ 2021 05 19;373:n1137. Epub 2021 May 19.

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: To estimate the direct and indirect effects of the covid-19 pandemic on mortality in 2020 in 29 high income countries with reliable and complete age and sex disaggregated mortality data.

Design: Time series study of high income countries.

Setting: Austria, Belgium, Czech Republic, Denmark, England and Wales, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, the Netherlands, New Zealand, Northern Ireland, Norway, Poland, Portugal, Scotland, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, and United States.

Participants: Mortality data from the Short-term Mortality Fluctuations data series of the Human Mortality Database for 2016-20, harmonised and disaggregated by age and sex.

Interventions: Covid-19 pandemic and associated policy measures.

Main Outcome Measures: Weekly excess deaths (observed deaths versus expected deaths predicted by model) in 2020, by sex and age (0-14, 15-64, 65-74, 75-84, and ≥85 years), estimated using an over-dispersed Poisson regression model that accounts for temporal trends and seasonal variability in mortality.

Results: An estimated 979 000 (95% confidence interval 954 000 to 1 001 000) excess deaths occurred in 2020 in the 29 high income countries analysed. All countries had excess deaths in 2020, except New Zealand, Norway, and Denmark. The five countries with the highest absolute number of excess deaths were the US (458 000, 454 000 to 461 000), Italy (89 100, 87 500 to 90 700), England and Wales (85 400, 83 900 to 86 800), Spain (84 100, 82 800 to 85 300), and Poland (60 100, 58 800 to 61 300). New Zealand had lower overall mortality than expected (-2500, -2900 to -2100). In many countries, the estimated number of excess deaths substantially exceeded the number of reported deaths from covid-19. The highest excess death rates (per 100 000) in men were in Lithuania (285, 259 to 311), Poland (191, 184 to 197), Spain (179, 174 to 184), Hungary (174, 161 to 188), and Italy (168, 163 to 173); the highest rates in women were in Lithuania (210, 185 to 234), Spain (180, 175 to 185), Hungary (169, 156 to 182), Slovenia (158, 132 to 184), and Belgium (151, 141 to 162). Little evidence was found of subsequent compensatory reductions following excess mortality.

Conclusion: Approximately one million excess deaths occurred in 2020 in these 29 high income countries. Age standardised excess death rates were higher in men than women in almost all countries. Excess deaths substantially exceeded reported deaths from covid-19 in many countries, indicating that determining the full impact of the pandemic on mortality requires assessment of excess deaths. Many countries had lower deaths than expected in children <15 years. Sex inequality in mortality widened further in most countries in 2020.
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http://dx.doi.org/10.1136/bmj.n1137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132017PMC
May 2021

Association of maternal lipid profile and gestational diabetes mellitus: A systematic review and meta-analysis of 292 studies and 97,880 women.

EClinicalMedicine 2021 Apr 16;34:100830. Epub 2021 Apr 16.

Department of Cardiovascular Sciences and Diabetes Research Centre, University of Leicester, Leicester LE1 7RH, United Kingdom.

Background: Gestational Diabetes Mellitus (GDM) is the most prevalent metabolic disorder during pregnancy, however, the association between dyslipidaemia and GDM remains unclear.

Methods: We searched Medline, Scopus, Web of Science, Cochrane, Maternity and Infant Care database (MIDIRS) and ClinicalTrials.gov up to February 2021 for relevant studies which reported on the circulating lipid profile during pregnancy, in women with and without GDM. Publications describing original data with at least one raw lipid [triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or very low-density lipoprotein cholesterol (VLDL-C)] measurement were retained. Data extraction was performed using a piloted data extraction form. The protocol was registered with PROSPERO (CRD42019139696).

Findings: A total of 292 studies, comprising of 97,880 pregnant women (28232 GDM and 69,648 controls) were included. Using random-effects meta-analysis models to pool study estimates, women with GDM had significantly higher (by 20%) TG levels, with a pooled weighted mean difference between GDM and non-GDM pregnancies of 0.388 mM (0.336, 0.439,  < 0.001). Further analyses revealed elevated TG levels occur in the first trimester and persist afterwards. Meta-regression analyses showed that differences in TG levels between women with GDM and healthy controls were significantly associated with age, BMI, study continent, OGTT procedure, and GDM diagnosis criteria.

Interpretation: Elevated lipids, particularly, TG, are associated with GDM.
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http://dx.doi.org/10.1016/j.eclinm.2021.100830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102708PMC
April 2021

Antihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Trial.

Stroke 2021 May 14:STROKEAHA120030790. Epub 2021 May 14.

Population Health Research Institute, Hamilton Health Sciences, ON, Canada (J.B., E.M.L., P.G., R.G.H., S.Y.).

Background And Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation-3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups.

Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed.

Results: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59-1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55-1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34-1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41-2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52-0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37-0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59-2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57-2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36-0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23-0.72]).

Conclusions: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.
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http://dx.doi.org/10.1161/STROKEAHA.120.030790DOI Listing
May 2021

Lower Risk of Hospitalisation for Heart Failure, Kidney Disease and Death with Sodium Glucose Co-Transporter-2 Compared to Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Regardless of Prior Cardiovascular or Kidney Disease: A Retrospective Cohort Study in UK Primary Care.

Diabetes Obes Metab 2021 May 11. Epub 2021 May 11.

Medical writing support Mr Jonathan Tulip and Mr Mark Greener Omegascientific UK ltd.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of cardiovascular and, or renal disease (CVRD). Dipeptidyl peptidase-4 inhibitors (DPP4i) have not shown these effects.

Methods: This retrospective cohort study propensity matched 24,438 patients receiving a SGLT2i 1:1 to a person receiving a DDP4i, stratified based on presence of CVRD. Primary outcomes were the time to each of the following: all-cause mortality, cardiovascular death or hospitalisation for heart failure (HF), myocardial infarction, stroke and chronic kidney disease (CKD).

Findings: Overall, SGLT2i were associated with reductions in all-cause mortality, cardiovascular mortality , HF hospitalisation and CKD hospitalisation compared with DPP4i. In patients with no CVRD history, SGLT2i were associated with reductions in all-cause mortality (0·71, 0·57-0·88; p=0·002), HF hospitalisation (0·76, 0·59-0·98; p=0·035) and CKD hospitalisation (0·75, 0·63-0·88; p<0·001). In patients with established cardiovascular disease (CVD) or at high risk, SGLT2i were associated with reductions in all-cause mortality (0·69, 0·59-0·82); p<0·001), cardiovascular mortality (0·76, 0·62-0·95; p=0·014), HF hospitalisation (0·73, 0·63-0·85; p<0·001), stroke hospitalisation (0·75, 0·59-0·94, p=0·013) and CKD hospitalisation (0·49, 0·43-0·54, p<0·001). Results were consistent across subgroups and sensitivity analyses.

Interpretation: SGLT2i were associated with reduced risk of all-cause mortality and hospitalisation for HF and CKD compared with DPP4-i, highlighting the need to introduce SGLT2i early in the management of T2D patients. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/dom.14437DOI Listing
May 2021

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

Diabetologia 2021 May 8. Epub 2021 May 8.

Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

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/m and last recorded HbA 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.
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http://dx.doi.org/10.1007/s00125-021-05463-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106514PMC
May 2021

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants.

Eur Heart J 2021 May 8. Epub 2021 May 8.

The Population Health Research Institute, Hamilton Health Sciences, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.

Aims: Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated.

Methods And Results: After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years.

Conclusion: The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.

Trial Registration Number: NCT00468923.
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http://dx.doi.org/10.1093/eurheartj/ehab225DOI Listing
May 2021

Microvascular Disease and Risk of Cardiovascular Events and Death From Intensive Treatment in Type 2 Diabetes: The ACCORDION Study.

Mayo Clin Proc 2021 06 2;96(6):1458-1469. Epub 2021 May 2.

Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, United Kingdom; Leicester Real World Evidence Unit, Leicester Diabetes Centre, Leicester General Hospital, United Kingdom.

Objective: To assess whether the presence of microvascular complications modifies the effect of intensive glucose reduction on long-term outcomes in patients with type 2 diabetes.

Patients And Methods: Using ACCORD and ACCORDION study data, we investigated the risk of the primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) or death in relation to the prerandomization type and extent of microvascular complications. Interaction terms were fitted in survival models to estimate the risk of both outcomes across levels of an overall microvascular disease score (range 0 to 100) and its individual components: diabetic nephropathy, retinopathy, and neuropathy.

Results: During a mean follow-up of 7.7 years, 1685 primary outcomes and 1806 deaths occurred in 9405 participants. The outcome-specific microvascular score was ≤30 in 97.9% of subjects for the primary outcome and in 98.5% for death. For participants with scores of 0 and 30, respectively, the 10-year absolute risk difference between intensive glucose control and standard treatment ranged from -0.8% (95% CI, -2.6, 1.1) to -3.0% -7.1, 1.1) for the primary outcome and from -0.5% (-2.1, 1.1) to 0.7% (-4.2, 5.6) for mortality. Retinopathy was associated with the largest effects, with a 10-year absolute risk difference of -6.5% (-11.1 to -2.0) for the primary outcome and -3.9% (-7.8 to 0.1) for mortality.

Conclusion: This hypothesis-generating study identifies diabetic retinopathy as predictor of the beneficial effect of intensive glucose control on the risk of cardiovascular disease and possibly death. Further long-term studies are required to confirm these findings.
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http://dx.doi.org/10.1016/j.mayocp.2020.08.047DOI Listing
June 2021

Inappropriate intensification of glucose-lowering treatment in older patients with type 2 diabetes: the global DISCOVER study.

BMJ Open Diabetes Res Care 2021 May;9(1)

Institute for Biometrics and Epidemiology, German Diabetes Center Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Dusseldorf, Germany.

Introduction: Although individualized target glycated hemoglobin (HbA) levels are recommended in older people with type 2 diabetes, studies report high levels of potential overtreatment. We aimed to investigate the proportion of older patients (aged ≥65 years) who potentially received an inappropriately intensive treatment (HbA level <7.0% (53.0 mmol/mol)) in a global study. Factors associated with intensive glycemic management and using glucose-lowering medications associated with a high risk of hypoglycemia (high-risk medications (insulin, sulfonylureas, and meglitinides)) were also assessed.

Research Design And Methods: DISCOVER is a 3-year observational study program of 15 992 people with type 2 diabetes initiating second-line glucose-lowering therapy in 38 countries. Data were collected at baseline (initiation of second-line therapy) and at 6, 12, and 24 months. Factors associated with an inappropriately intensive treatment or using high-risk medications were assessed using a hierarchical regression model.

Results: Of the 3344 older patients with baseline HbA data in our analytic cohort, 23.5% received inappropriate treatment intensification. Among those who had follow-up HbA data, 55.2%, 54.2%, and 53.5% were inappropriately tightly controlled at 6, 12, and 24 months, respectively, with higher proportions in high-income than in middle-income countries. The proportion of patients receiving high-risk medications was higher in middle-income countries than in high-income countries. Gross national income (per US$5000 increment) was associated with increased odds of inappropriately intensive treatment but with decreased odds of receiving high-risk medications.

Conclusions: A large proportion of older DISCOVER patients received an inappropriately intensive glucose-lowering treatment across the 2 years of follow-up, with substantial regional variation. The use of high-risk medications in these patients is particularly concerning.
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http://dx.doi.org/10.1136/bmjdrc-2020-001585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098925PMC
May 2021

Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.

Lancet 2021 05 30;397(10286):1711-1724. Epub 2021 Apr 30.

Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.

Background: COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.

Methods: We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region.

Findings: Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories.

Interpretation: Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.

Funding: Medical Research Council.
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http://dx.doi.org/10.1016/S0140-6736(21)00634-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087292PMC
May 2021

Gait Speed as a Predictor for Diabetes Incidence in People with or at Risk of Knee Osteoarthritis: A Longitudinal Analysis from the Osteoarthritis Initiative.

Int J Environ Res Public Health 2021 04 21;18(9). Epub 2021 Apr 21.

Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia.

Background: This study examined the association between baseline gait speed with incident diabetes mellitus (DM) among people with or at elevated risk for knee OA.

Materials And Methods: Participants from the Osteoarthritis Initiative, aged 45 to 79 years, where included. Participants with or at risk of knee OA from baseline to the 96-month visit were included. Participants with self-reported DM at baseline were excluded. DM incidence was followed over the 4-time points. Gait speed was measured at baseline using a 20-m walk test. Generalized estimating equations with logistic regression were utilized for analyses. Receiver operator characteristic curves and area under the curve were used to determine the cutoff score for baseline speed.

Results: Of the 4313 participants included in the analyses (58.7% females), 301 participants had a cumulative incidence of DM of 7.0% during follow-up. Decreased gait speed was a significant predictor of incident DM (RR 0.44, = 0.018). The threshold for baseline gait speed that predicted incident DM was 1.32 m/s with an area under the curve of 0.59 ( < 0.001).

Conclusions: Baseline gait speed could be an important screening tool for identifying people at risk of incident diabetes, and the determined cutoff value for gait speed should be examined in future research.
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http://dx.doi.org/10.3390/ijerph18094414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122394PMC
April 2021

Biochemical Urine Testing of Medication Adherence and Its Association With Clinical Markers in an Outpatient Population of Type 2 Diabetes Patients: Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT).

Diabetes Care 2021 Apr 23. Epub 2021 Apr 23.

Department of Internal Medicine/Nephrology, Ziekenhuis Groep Twente, Almelo, the Netherlands.

Objective: To assess adherence to the three main drug classes in real-world patients with type 2 diabetes using biochemical urine testing, and to determine the association of nonadherence with baseline demographics, treatment targets, and complications.

Research Design And Methods: Analyses were performed of baseline data on 457 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT) study. Adherence to oral antidiabetics (OADs), antihypertensives, and statins was determined by analyzing baseline urine samples using liquid chromatography-tandem mass spectrometry. Primary outcomes were microvascular and macrovascular complications and treatment targets of LDL cholesterol, HbA, and blood pressure. These were assessed cross-sectionally at baseline.

Results: Overall, 89.3% of patients were identified as adherent. Adherence rates to OADs, antihypertensives, and statins were 95.7, 92.0, and 95.5%, respectively. The prevalence of microvascular (81.6 vs. 66.2%; = 0.029) and macrovascular complications (55.1 vs. 37.0%; = 0.014) was significantly higher in nonadherent patients. The percentage of patients who reached an LDL cholesterol target of ≤2.5 mmol/L was lower (67.4 vs. 81.1%; = 0.029) in nonadherent patients. Binary logistic regression indicated that higher BMI, current smoking, elevated serum LDL cholesterol, high HbA, presence of diabetic kidney disease, and presence of macrovascular disease were associated with nonadherence.

Conclusions: Although medication adherence of real-world type 2 diabetes patients managed in specialist care was relatively high, the prevalence of microvascular and macrovascular complications was significantly higher in nonadherent patients, and treatment targets were reached less frequently. This emphasizes the importance of objective detection and tailored interventions to improve adherence.
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http://dx.doi.org/10.2337/dc20-2533DOI Listing
April 2021

Unequal impact of the COVID-19 crisis on minority ethnic groups: a framework for understanding and addressing inequalities.

J Epidemiol Community Health 2021 Apr 21. Epub 2021 Apr 21.

Public Health and Policy, University of Liverpool, Liverpool, UK.

Minority ethnic groups have been disproportionately affected by the COVID-19 pandemic. While the exact reasons for this remain unclear, they are likely due to a complex interplay of factors rather than a single cause. Reducing these inequalities requires a greater understanding of the causes. Research to date, however, has been hampered by a lack of theoretical understanding of the meaning of 'ethnicity' (or race) and the potential pathways leading to inequalities. In particular, quantitative analyses have often adjusted away the pathways through which inequalities actually arise (ie, mediators for the effect of interest), leading to the effects of social processes, and particularly structural racism, becoming hidden. In this paper, we describe a framework for understanding the pathways that have generated ethnic (and racial) inequalities in COVID-19. We suggest that differences in health outcomes due to the pandemic could arise through six pathways: (1) differential exposure to the virus; (2) differential vulnerability to infection/disease; (3) differential health consequences of the disease; (4) differential social consequences of the disease; (5) differential effectiveness of pandemic control measures and (6) differential adverse consequences of control measures. Current research provides only a partial understanding of some of these pathways. Future research and action will require a clearer understanding of the multiple dimensions of ethnicity and an appreciation of the complex interplay of social and biological pathways through which ethnic inequalities arise. Our framework highlights the gaps in the current evidence and pathways that need further investigation in research that aims to address these inequalities.
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http://dx.doi.org/10.1136/jech-2020-216061DOI Listing
April 2021

Long COVID - metabolic risk factors and novel therapeutic management.

Nat Rev Endocrinol 2021 Apr 19. Epub 2021 Apr 19.

Diabetes Center Bochum-Hattingen, St. Josef-Hospital, Ruhr-University, Bochum, Germany.

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http://dx.doi.org/10.1038/s41574-021-00495-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054121PMC
April 2021

Metformin for Preventing Type 2 Diabetes Mellitus in Women with a Previous Diagnosis of Gestational Diabetes: A Narrative Review.

Semin Reprod Med 2020 Nov 15;38(6):366-376. Epub 2021 Apr 15.

School of Medicine, Deakin University, Geelong, Australia.

Women with a history of gestational diabetes mellitus (GDM) are at greater risk of developing type 2 diabetes mellitus (T2DM) when compared with women who have not had GDM. To delay or prevent T2DM, guidelines recommend regular screening in the primary care setting and lifestyle interventions that are largely focused on dietary and physical activity modifications. As the postpartum period can be challenging for women, uptake and engagement in screening and lifestyle interventions have been poor. Poor uptake and engagement places women with a history of GDM at heightened risk for future morbidity and development of T2DM. Metformin has been a longstanding and safe treatment for the control of blood glucose in people with T2DM. Research has supported the efficacy of metformin, used as an adjunct to a lifestyle intervention or as a stand-alone treatment, in preventing T2DM in people at high risk of T2DM. Findings from longitudinal studies have demonstrated the potential for metformin to reduce conversion to T2DM when used by women with a previous diagnosis of GDM. This review examines the potential effectiveness of metformin to reduce the incidence of T2DM among women with a previous diagnosis of GDM in the "real-world" setting.
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http://dx.doi.org/10.1055/s-0041-1727203DOI Listing
November 2020

Associations between second-line glucose-lowering combination therapies with metformin and HbA1c, body weight, quality of life, hypoglycaemic events and glucose-lowering treatment intensification: The DISCOVER study.

Diabetes Obes Metab 2021 Apr 14. Epub 2021 Apr 14.

AstraZeneca, Gaithersburg, Maryland, USA.

Aim: To explore the effects of second-line combination therapies with metformin on body weight, HbA1c and health-related quality of life, as well as the risks of hypoglycaemia and further treatment intensification in the DISCOVER study, a 3-year, prospective, global observational study of patients with type 2 diabetes initiating second-line glucose-lowering therapy.

Materials And Methods: Adjusted changes from baseline in weight, HbA1c and 36-item Short Form Health Survey version 2 (SF-36v2) summary scores at 6, 12, 24 and 36 months were assessed using linear mixed models. Risk of hypoglycaemia and further intensification were assessed using interval censored analyses.

Results: At baseline, 7613 patients received metformin in combination with a sulphonylurea (SU; 40.9%), a dipeptidyl peptidase-4 (DPP-4) inhibitor (48.3%), a sodium-glucose co-transporter-2 (SGLT-2) inhibitor (8.3%) or a glucagon-like peptide-1 (GLP-1) receptor agonist (2.4%). After 36 months, all combinations showed similar reductions in HbA1c (0.8%-1.0%), however, metformin plus a DPP-4 inhibitor, an SGLT-2 inhibitor or a GLP-1 receptor agonist was associated with greater weight loss (1.9, 2.9 and 5.0 kg, respectively) than metformin plus an SU (1.3 kg, P < .0001). Proportions of further treatment intensification were similar across combinations (19.9%-26.2%). Patients prescribed metformin plus an SU more often reported one or more hypoglycaemic events (11.9%) than other combinations (3.9%-6.4%, P < .0001). SF-36v2 summary scores were typically lowest among patients prescribed metformin and an SU.

Conclusions: Combinations of metformin with an SU were associated with the lowest weight reduction, highest risk of hypoglycaemia and lower SF-36v2 scores.
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http://dx.doi.org/10.1111/dom.14400DOI Listing
April 2021

Prevalence and progression of chronic kidney disease among patients with type 2 diabetes: Insights from the DISCOVER study.

Diabetes Obes Metab 2021 Apr 14. Epub 2021 Apr 14.

Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA.

We report the prevalence and change in severity of chronic kidney disease (CKD) in DISCOVER, a global, 3-year, prospective, observational study of patients with type 2 diabetes (T2D) initiating second-line glucose-lowering therapy. CKD stages were defined according to estimated glomerular filtration rate (eGFR). Overall, 7843 patients from 35 countries had a baseline serum creatinine measurement. Of these (56.7% male; mean age: 58.1 years; mean eGFR: 87.5 mL/min/1.73 m ), baseline prevalence estimates for stage 0-1, 2, 3 and 4-5 CKD were 51.4%, 37.7%, 9.4% and 1.4%, respectively. A total of 5819 patients (74.2%) also had at least one follow-up serum creatinine measurement (median time between measurements: 2.9 years, interquartile range: 1.9-3.0 years). Mean eGFR decreased slightly to 85.7 mL/min/1.73 m over follow-up. CKD progression (increase of ≥1 stage) occurred in 15.7% of patients, and regression (decrease of ≥1 stage) in 12.0%. In summary, a substantial proportion of patients with T2D developed CKD or had CKD progression after the initiation of second-line therapy. Renal function should be regularly monitored in these patients, to ensure early CKD diagnosis and treatment.
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http://dx.doi.org/10.1111/dom.14401DOI Listing
April 2021

Is Socio-economic Deprivation Associated with One Year Post-operative Mortality Following Major Amputation for Chronic Limb Threatening Ischaemia?

Eur J Vasc Endovasc Surg 2021 Apr 10. Epub 2021 Apr 10.

Leicester Vascular Institute, University Hospitals of Leicester NHS Trust, Leicester, UK.

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http://dx.doi.org/10.1016/j.ejvs.2021.02.020DOI Listing
April 2021

Glycemic Control and Prevention of Diabetic Complications in Low- and Middle-Income Countries: An Expert Opinion.

Diabetes Ther 2021 May 10;12(5):1491-1501. Epub 2021 Apr 10.

Diabetes Research Centre, University of Leicester, Leicester, UK.

Introduction: Trends on glycemic control and diabetes complications are known for high-income countries, but comprehensive data from low- and middle-income countries (LMIC) are lacking.

Methods: This is an expert opinion based on two retrospective studies. Here we examine the recent subset analysis of relevant data from the IDMPS Wave 7 (International Diabetes Management-Practices Study, 2015-2016) and the GOAL study conducted in multiple LMICs.

Results: Wave 7 sub-analysis was performed in 6113 people with type 2 diabetes from 24 LMIC. Poorly controlled diabetes (hemogloblin A1c [HbA1c] ≥ 7%) was found in 58.6, 73.0 and 78.3% of participants with diabetes duration of < 5, 5-12 and > 12 years, respectively (in association with a high prevalence of macro- and microvascular complications). Moreover, 37.7% of participants with diabetes duration of 5-12 years were treated only with oral antihyperglycemic drugs. The GOAL study investigated the efficacy of insulin in 2704 poorly controlled participants (mean HbA1c 9.7%; diabetes duration 10.1 ± 6.7 years; 10 LMIC). A significant 2% reduction in mean HbA1c levels was observed after 12 months of treatment. Only 7.2% of participants experienced a symptomatic episode of hypoglycemia (nocturnal or severe hypoglycemia events were infrequent).

Conclusion: The rate of well-controlled participants (HbA1c < 7.0%) in the Wave 7 sub-analysis was lower than that observed in the USA (NHANES survey) or in European countries (GUIDANCE study), and the incidence of microvascular complications was higher. The GOAL study showed that insulin treatment improves glycemic control and reduces this gap. The Expert Panel recommends intensifying diabetes treatment as soon as possible, as well as patients' education and other preventive measures, initiatives which require modest costs compared to hospitalization and treatment of diabetes complications.
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http://dx.doi.org/10.1007/s13300-021-00997-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099945PMC
May 2021

Ramadan and COVID-19 vaccine hesitancy-a call for action.

Lancet 2021 04 7;397(10283):1443-1444. Epub 2021 Apr 7.

Diabetes Research Centre, University of Leicester, Leicester, UK; the Centre for Black Minority Health, University of Leicester, Leicester, UK.

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http://dx.doi.org/10.1016/S0140-6736(21)00779-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026169PMC
April 2021

Quantifying the association between ethnicity and COVID-19 mortality: a national cohort study protocol.

BMJ Open 2021 04 7;11(4):e045286. Epub 2021 Apr 7.

Nuffield Department of Primary Care Sciences, University of Oxford, Oxford, UK.

Introduction: Recent evidence suggests that ethnic minority groups are disproportionately at increased risk of hospitalisation and death from SARS-CoV-2 infection. Population-based evidence on potential explanatory factors across minority groups and within subgroups is lacking. This study aims to quantify the association between ethnicity and the risk of hospitalisation and mortality due to COVID-19.

Methods And Analysis: This is a retrospective cohort study of adults registered across a representative and anonymised national primary care database (QResearch) that includes data on 10 million people in England. Sociodemographic, deprivation, clinical and domicile characteristics will be summarised and compared across ethnic subgroups (categorised as per 2011 census). Cox models will be used to calculate HR for hospitalisation and COVID-19 mortality associated with ethnic group. Potential confounding and explanatory factors (such as demographic, socioeconomic and clinical) will be adjusted for within regression models. The percentage contribution of distinct risk factor classes to the excess risks seen in ethnic groups/subgroups will be calculated.

Ethics And Dissemination: The study has undergone ethics review in accordance with the QResearch agreement (reference OX102). Findings will be disseminated through peer-reviewed manuscripts, presentations at scientific meetings and conferences with national and international stakeholders.
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http://dx.doi.org/10.1136/bmjopen-2020-045286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029035PMC
April 2021

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

Lancet Diabetes Endocrinol 2021 05 30;9(5):293-303. Epub 2021 Mar 30.

National Diabetes Audit Programme, NHS England & Improvement, London, UK; NHS England and NHS Improvement, London, UK; Department of Diabetes and Endocrinology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK; Division of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.

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.
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http://dx.doi.org/10.1016/S2213-8587(21)00050-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009618PMC
May 2021

Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study.

BMJ 2021 03 31;372:n693. Epub 2021 Mar 31.

Institute of Health Informatics, University College London, London NW1 2DA, UK

Objective: To quantify rates of organ specific dysfunction in individuals with covid-19 after discharge from hospital compared with a matched control group from the general population.

Design: Retrospective cohort study.

Setting: NHS hospitals in England.

Participants: 47 780 individuals (mean age 65, 55% men) in hospital with covid-19 and discharged alive by 31 August 2020, exactly matched to controls from a pool of about 50 million people in England for personal and clinical characteristics from 10 years of electronic health records.

Main Outcome Measures: Rates of hospital readmission (or any admission for controls), all cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30 September 2020. Variations in rate ratios by age, sex, and ethnicity.

Results: Over a mean follow-up of 140 days, nearly a third of individuals who were discharged from hospital after acute covid-19 were readmitted (14 060 of 47 780) and more than 1 in 10 (5875) died after discharge, with these events occurring at rates four and eight times greater, respectively, than in the matched control group. Rates of respiratory disease (P<0.001), diabetes (P<0.001), and cardiovascular disease (P<0.001) were also significantly raised in patients with covid-19, with 770 (95% confidence interval 758 to 783), 127 (122 to 132), and 126 (121 to 131) diagnoses per 1000 person years, respectively. Rate ratios were greater for individuals aged less than 70 than for those aged 70 or older, and in ethnic minority groups compared with the white population, with the largest differences seen for respiratory disease (10.5 (95% confidence interval 9.7 to 11.4) for age less than 70 years 4.6 (4.3 to 4.8) for age ≥70, and 11.4 (9.8 to 13.3) for non-white 5.2 (5.0 to 5.5) for white individuals).

Conclusions: Individuals discharged from hospital after covid-19 had increased rates of multiorgan dysfunction compared with the expected risk in the general population. The increase in risk was not confined to the elderly and was not uniform across ethnicities. The diagnosis, treatment, and prevention of post-covid syndrome requires integrated rather than organ or disease specific approaches, and urgent research is needed to establish the risk factors.
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http://dx.doi.org/10.1136/bmj.n693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010267PMC
March 2021

Evaluation of an 8-Week Vegan Diet on Plasma Trimethylamine-N-Oxide and Postchallenge Glucose in Adults with Dysglycemia or Obesity.

J Nutr 2021 Mar 30. Epub 2021 Mar 30.

Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, United Kingdom.

Background: Trimethylamine N-oxide (TMAO), a metabolite generated by the gut in response (in part) to meat consumption, is linked to poor cardiometabolic health.

Objectives: We investigate the effect of an 8-week vegan diet, followed by a 4-week period of unrestricted diet, on glucose tolerance and plasma TMAO in human omnivores with obesity or dysglycemia.

Methods: This interventional single-group prospective trial involved 23 regular meat eaters with dysglycemia [glycated hemoglobin ≥ 5.7% and ≤8% (39-64 mmol/mol)], or obesity (ΒΜΙ ≥ 30 kg/m2) aged 57.8 ± 10.0 years. Participants [14 men (60.9%) and 9 women (39.1%)] were supported in following a vegan diet for 8 weeks, followed by 4 weeks of unrestricted diet. The primary outcomes (plasma TMAO and glucose) were assessed at baseline, during the vegan diet (weeks 1 and 8), and after the unrestricted diet period (week 12). TMAO was assessed after fasting and glucose was measured as a time-averaged total AUC using a 180-minute oral-glucose-tolerance test. Generalized estimating equation models with an exchangeable correlation structure were used to assess changes from baseline, adjusting for age, sex, ethnicity, and weight.

Results: TMAO levels (marginal mean) were reduced after weeks 1 and 8 of a vegan diet compared to baseline, from 10.7 (97.5% CI, 6.61-17.3) μmol/L to 5.66 (97.5% CI, 4.56-7.02) μmol/L and 6.38 (97.5% CI, 5.25-7.74) μmol/L, respectively; however, levels rebounded at week 12 after resumption of an unrestricted diet (17.5 μmol/L; 97.5% CI, 7.98-38.4). Postprandial glucose levels (marginal means) were reduced after weeks 1 and 8 compared to baseline, from 8.07 (97.5% CI, 7.24-8.90) mmol/L to 7.14 (97.5% CI, 6.30-7.98) mmol/L and 7.34 (97.5% CI, 6.63-8.04) mmol/L, respectively. Results for glucose and TMAO were independent of weight loss. Improvements in the lipid profile and markers of renal function were observed at week 8.

Conclusions: These findings suggest that a vegan diet is an effective strategy for improving glucose tolerance and reducing plasma TMAO in individuals with dysglycemia or obesity. This study was registered at clinicaltrials.gov as NCT03315988.
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http://dx.doi.org/10.1093/jn/nxab046DOI Listing
March 2021