General Practice and Primary Care - Research Publications
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ItemNo Preview AvailableEffect of Conventional Lifestyle Interventions on Type 2 Diabetes Incidence by Glucose-Defined Prediabetes Phenotype: An Individual Participant Data Meta-analysis of Randomized Controlled Trials.(American Diabetes Association, 2023-11-01)OBJECTIVE: To examine whether the effect of conventional lifestyle interventions on type 2 diabetes incidence differs by glucose-defined prediabetes phenotype. RESEARCH DESIGN AND METHODS: We searched multiple databases until 1 April 2023 for randomized controlled trials that recruited people with isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and impaired fasting glucose plus impaired glucose tolerance (IFG+IGT). Individual participant data were pooled from relevant trials and analyzed through random-effects models with use of the within-trial interactions approach. RESULTS: Four trials with 2,794 participants (mean age 53.0 years, 60.7% men) were included: 1,240 (44.4%), 796 (28.5%), and 758 (27.1%) had i-IFG, i-IGT, and IFG+IGT, respectively. After a median of 2.5 years, the pooled hazard ratio for diabetes incidence in i-IFG was 0.97 (95% CI 0.66, 1.44), i-IGT 0.65 (0.44, 0.96), and IFG+IGT 0.51 (0.38, 0.68; Pinteraction = 0.01). CONCLUSIONS: Conventional lifestyle interventions reduced diabetes incidence in people with IGT (with or without IFG) but not in those with i-IFG.
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ItemRisk of Long COVID in People Infected With Severe Acute Respiratory Syndrome Coronavirus 2 After 2 Doses of a Coronavirus Disease 2019 Vaccine: Community-Based, Matched Cohort Study(OXFORD UNIV PRESS INC, 2022-09-02)We investigated long COVID incidence by vaccination status in a random sample of UK adults from April 2020 to November 2021. Persistent symptoms were reported by 9.5% of 3090 breakthrough severe acute respiratory syndrome coronavirus 2 infections and 14.6% of unvaccinated controls (adjusted odds ratio, 0.59 [95% confidence interval, .50-.69]), emphasizing the need for public health initiatives to increase population-level vaccine uptake.
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ItemRemission of type 2 diabetes and improved diastolic function by combining structured exercise with meal replacement and food reintroduction among young adults: the RESET for REMISSION randomised controlled trial protocol(BMJ PUBLISHING GROUP, 2022-09)INTRODUCTION: Type 2 diabetes mellitus (T2DM) onset before 40 years of age has a magnified lifetime risk of cardiovascular disease. Diastolic dysfunction is its earliest cardiac manifestation. Low energy diets incorporating meal replacement products can induce diabetes remission, but do not lead to improved diastolic function, unlike supervised exercise interventions. We are examining the impact of a combined low energy diet and supervised exercise intervention on T2DM remission, with peak early diastolic strain rate, a sensitive MRI-based measure, as a key secondary outcome. METHODS AND ANALYSIS: This prospective, randomised, two-arm, open-label, blinded-endpoint efficacy trial is being conducted in Montreal, Edmonton and Leicester. We are enrolling 100 persons 18-45 years of age within 6 years' T2DM diagnosis, not on insulin therapy, and with obesity. During the intensive phase (12 weeks), active intervention participants adopt an 800-900 kcal/day low energy diet combining meal replacement products with some food, and receive supervised exercise training (aerobic and resistance), three times weekly. The maintenance phase (12 weeks) focuses on sustaining any weight loss and exercise practices achieved during the intensive phase; products and exercise supervision are tapered but reinstituted, as applicable, with weight regain and/or exercise reduction. The control arm receives standard care. The primary outcome is T2DM remission, (haemoglobin A1c of less than 6.5% at 24 weeks, without use of glucose-lowering medications during maintenance). Analysis of remission will be by intention to treat with stratified Fisher's exact test statistics. ETHICS AND DISSEMINATION: The trial is approved in Leicester (East Midlands - Nottingham Research Ethics Committee (21/EM/0026)), Montreal (McGill University Health Centre Research Ethics Board (RESET for remission/2021-7148)) and Edmonton (University of Alberta Health Research Ethics Board (Pro00101088). Findings will be shared widely (publications, presentations, press releases, social media platforms) and will inform an effectiveness trial. TRIAL REGISTRATION NUMBER: ISRCTN15487120.
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ItemAssociation of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales(LIPPINCOTT WILLIAMS & WILKINS, 2022-09-20)BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear. METHODS: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history. RESULTS: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0-22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21-1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3-35.2) in week 1 to 1.80 (95% CI, 1.50-2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses. CONCLUSIONS: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.
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ItemTreatment patterns and glycated haemoglobin levels over 36 months in individuals with type 2 diabetes initiating second-line glucose-lowering therapy: The global DISCOVER study(WILEY, 2023-01)AIMS: To describe glucose-lowering treatment regimens and glycated haemoglobin (HbA1c) trajectories in individuals with type 2 diabetes (T2D) over 36 months of follow-up from the start of second-line therapy. MATERIALS AND METHODS: This data analysis from the 3-year, observational DISCOVER study programme included 14 687 participants from 37 countries with T2D initiating second-line glucose-lowering therapy. Treatment and HbA1c data were collected at baseline (start of second-line therapy) and at 6, 12, 24 and 36 months. Treatment regimen changes over follow-up were analysed using the McNemar test, with carry-forward imputation for intermediate missing values. RESULTS: A total of 11 592 participants had treatment data at baseline and 36 months, and 11 882 had HbA1c data at baseline. At baseline and 36 months, respectively, rates of oral monotherapy use were 12.1% and 12.4% (P = 0.22), rates of dual oral therapy use were 63.4% and 47.6% (P < 0.0001), rates of ≥ triple oral therapy use were 17.5% and 25.4% (P < 0.0001), and rates of injectable treatment use were 7.0% and 13.7% (P < 0.0001). Use of injectable drugs was most common among participants with an HbA1c level ≥64 mmol/mol (≥8.0%). Overall, 42.9% of participants changed treatment during follow-up. Mean HbA1c levels at baseline and 6 months were 67 mmol/mol (8.3%) and 55 mmol/mol (7.2%), respectively, remaining stable thereafter. CONCLUSIONS: Dual oral therapy was the most common treatment regimen at the start of second-line treatment, and over half of the participants remained on the same treatment during follow-up.
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ItemAssociation of country economy and socioeconomic factors on risk factor control for primary prevention of cardiovascular disease in patients with diabetes mellitus: Insights from the DISCOVER study(ELSEVIER, 2022-09-01)BACKGROUND: We sought to describe global patterns in achievement of risk factor control for primary prevention in patients with T2D and explore the association of country's GNI/capita with risk factor control. METHODS: The DISCOVER study is a prospective, observational study of patients with T2D from 38 countries enrolled at initiation of second-line glucose-lowering therapy. We examined achievement of risk factor control (glycosylated hemoglobin <7%, blood pressure <140/90 mmHg, prescription of a statin) at 3 years among those without optimal control at baseline. Countries were stratified by gross national income (GNI)/capita, from 2017). We examined the impact of country GNI/capita with achievement of risk factor control. FINDINGS: Our cohort included 9613 patients with T2D and without baseline cardiovascular disease (mean age 57.2 ± 8.7 years, 47.9% women). At baseline, 6354/7646 patients (83.1%) had suboptimal glucose control, 3449/9200 patients (37.5%) had suboptimal BP control, and 2800/4221 patients (66.7%) were not on an appropriate statin (sample sizes differed due to missing covariate data). Optimal control at 3 years of follow-up was achieved in 41% (glucose), 56% (blood pressure), and 29% (statins) of patients. There was significant variability in achievement of risk factor control across countries but no association between country GNI/capita with achievement of risk factor control (p > 0.08 for all). INTERPRETATION: In a global, prospective study of patients with T2D, we found that cardiovascular risk factor control achievement was suboptimal despite 3 years of follow-up in specialized health care systems. Neither country-level nor patient-level socioeconomic factors fully explained this finding.
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ItemAssociations between frailty trajectories and cardiovascular, renal, and mortality outcomes in chronic kidney disease(WILEY, 2022-10)BACKGROUND: Frailty is characterized by the loss of biological reserves and vulnerability to adverse outcomes. In individuals with chronic kidney disease (CKD), numerous pathophysiological factors may be responsible for frailty development including inflammation, physical inactivity, reduced energy intake, and metabolic acidosis. Given that both CKD and frailty incur a significant healthcare burden, it is important to understand the relationship of CKD and frailty in real-world routine clinical practice, and how simple frailty assessment methods (e.g. frailty indexes) may be useful. We investigated the risk of frailty development in CKD and the impact of frailty status on mortality and end-stage kidney disease (ESKD). METHODS: A retrospective cohort study using primary care records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics and the UK Office for National Statistics was undertaken in 819 893 participants aged ≥40 years, of which 140 674 had CKD. Frailty was defined using an electronic frailty index, generated electronically from primary care records. Cox proportional hazard and flexible parametric survival models were used to investigate the risk of developing frailty and the effect of frailty on risk of all-cause and cardiovascular mortality, and ESKD. RESULTS: The mean age of those with CKD was 77.5 (SD 9.7) years [61.0 (SD 12.1) years in no-CKD group]; 62.0% of the CKD group were female (compared with 53.3% in no-CKD group). The mean estimated glomerular filtration rate of those with CKD was 46.1 (SD 9.9) mL/min/1.73 m2 . The majority of those with CKD (75.3%) were frail [vs. 45.4% in those without CKD (no-CKD)]. Over 3 years (median), 69.5% of those with CKD developed frailty. Compared with no-CKD, those with CKD had increased rates of developing mild (hazard ratio: 1.02; 95% confidence interval: 1.01-1.04), moderate (1.30; 1.26-1.34), and severe (1.50; 1.37-1.65) frailty. Mild (1.22; 1.19-1.24), moderate (1.60; 1.56-1.63), and severe (2.16; 2.11-2.22) frailty was associated with increased rates of all-cause and cardiovascular-related mortality (mild 1.35; 1.31-1.39; moderate 1.96; 1.90-2.02; and severe 2.91; 2.81-3.02). All stages of frailty significantly increased ESKD rates. CONCLUSIONS: Frailty is highly prevalent and associated with adverse outcomes in people with CKD, including mortality and risk of ESKD. Preventative interventions should be initiated to mitigate the development of frailty. The use of a simple frailty index, generated electronically from health records, can predict outcomes and may aid prioritization for management of people with frailty.
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ItemSignificant reduction in chronic kidney disease progression with sodium-glucose cotransporter-2 inhibitors compared to dipeptidyl peptidase-4 inhibitors in adults with type 2 diabetes in a UK clinical setting: An observational outcomes study based on international guidelines for kidney disease(WILEY, 2022-07-06)AIMS: To confirm the reno-protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with dipeptidyl peptidase-4 (DPP-4) inhibitors on the onset and progression of chronic kidney disease (CKD) in routine clinical practice. MATERIALS AND METHODS: We conducted a retrospective cohort study using the Clinical Practice Research Datalink Aurum database linked to Hospital Episode Statistics. The primary outcome was risk of the composite CKD endpoint based on the recent consensus guidelines for kidney disease: >40% decline in estimated glomerular filtration rate (eGFR), kidney death or end-stage kidney disease (ESKD; a composite of kidney transplantation, maintenance of dialysis, sustained low eGFR <15 ml/min/1.73m² or diagnosis of ESKD). Secondary outcomes were components of the composite CKD endpoint, analysed separately. Patients were propensity-score-matched 1:1 for SGLT2 inhibitor versus DPP-4 inhibitor use. RESULTS: A total of 131 824 people with type 2 diabetes (T2D) were identified; 79.0% had no known history of CKD. During a median follow-up of 2.1 years, SGLT2 inhibitor initiation was associated with lower risk of progression to composite kidney endpoints than DPP-4 inhibitor initiation (7.48 vs. 11.77 events per 1000 patient-years, respectively). Compared with DPP-4 inhibitor initiation, SGLT2 inhibitor initiation was associated with reductions in the primary composite CKD endpoint (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.56-0.74), all-cause mortality (HR 0.74, 95% CI 0.64-0.86) and ESKD (HR 0.37, 95% CI 0.25-0.55), reduced the rate of sustained low eGFR (HR 0.33, 95% CI 0.19-0.57), and reduced diagnoses of ESKD in primary care (HR 0.04, 95% CI 0.01-0.18). Results were consistent across subgroup and sensitivity analyses. CONCLUSIONS: In adults with T2D, initiation of an SGLT2 inhibitor was associated with a significantly reduced risk of CKD progression and death compared with initiation of a DPP-4 inhibitor.