International Variation in Case Fatality After Major Coronary or Cerebrovascular Events in Individuals With Type 2 Diabetes: Evidence From ADVANCE, TECOS, and EXSCEL.

Objective: To examine differences in case-fatality incidence among individuals with type 2 diabetes after major coronary or cerebrovascular events by geographic region and country income level.

Research Design And Methods: We studied ADVANCE, TECOS, and EXSCEL participants who experienced within-trial major coronary (fatal or nonfatal myocardial infarction or sudden cardiac death) or cerebrovascular (fatal or nonfatal stroke) events. Case fatality was defined as death at the time or within 30 days of an event.

Impact of changes in conventional risk factors induced by once-weekly GLP-1 receptor agonist exenatide on cardiovascular outcomes: an EXSCEL post hoc analysis.

Background: The objective of this study was to examine the degree to which conventional cardiovascular (CV) risk factor changes induced by once-weekly exenatide (EQW) might explain the placebo-controlled differences in CV outcomes observed in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

Methods: We entered participant-level risk factor values over time into a validated type 2 diabetes-specific clinical outcomes model to estimate event rates, and compared simulated with observed relative risk changes in EXSCEL. We performed simulations for each participant to minimize uncertainty and to optimize confidence interval precision around risk point estimates.

Glucocorticoid-induced hyperglycaemia in hospitalised adults: A matched cohort study (2013-2023).

Aims: To compare the risk of new-onset hyperglycaemia between inpatients treated versus non-treated with systemic glucocorticoids and identify factors associated with glucocorticoid-induced hyperglycaemia (GIH).

Materials And Methods: We conducted a cohort study using electronic healthcare records of adults admitted to the Oxford University Hospitals between 2013 and 2023. We excluded patients with diabetes or prescribed systemic glucocorticoids before admission.

Risk factors for bone fractures in type 2 diabetes and the impact of once-weekly exenatide: insights from an EXSCEL post-hoc analysis.

Aims: We investigated bone fracture predictors in people with T2D enrolled in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) and evaluated the effects of once-weekly exenatide (EQW) on incident bone fractures.

Methods: EXSCEL randomised 14,752 people to EQW 2 mg or placebo with a median follow-up of 3.2 years.

Glucocorticoid treatment and new-onset hyperglycaemia and diabetes in people living with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Introduction: In people living with chronic obstructive pulmonary disease (COPD), we aimed to estimate: (1) the prevalence of glucocorticoid-induced hyperglycaemia (GIH); (2) whether the prevalence of GIH varies by age, baseline diabetes status, treatment duration, ascertainment of glycaemia, definition of hyperglycaemia, study design and year of publication; and (3) the relative risk (RR) of new-onset hyperglycaemia in exposed vs non-exposed to systemic glucocorticoids.

Methods: We searched electronic databases until 9 November 2023 for randomised controlled trials and observational studies including adults diagnosed with COPD, with or without diabetes at baseline, using systemic glucocorticoids equivalent to prednisolone ≥5 mg/day for ≥3 days if exposed. Hyperglycaemia was defined as a blood glucose above a study-specific cut-off.

Younger-onset compared with later-onset type 2 diabetes: an analysis of the UK Prospective Diabetes Study (UKPDS) with up to 30 years of follow-up (UKPDS 92).

Background: Younger-onset type 2 diabetes is associated with accelerated complications. We assessed whether complications and mortality rates differed for younger age compared with older age at diagnosis over 30 years of follow-up.

Methods: In this study, we used data from the UKPDS, collected between 1977 and 2007, of participants aged 25-65 years with newly diagnosed type 2 diabetes with younger-onset (younger than 40 years) or later-onset (40 years or older), and without diabetes autoantibodies.

Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial.

Aim: The decline in estimated glomerular filtration rate (eGFR), a significant predictor of cardiovascular disease (CVD), occurs heterogeneously in people with diabetes because of various risk factors. We investigated the role of eGFR decline in predicting CVD events in people with type 2 diabetes in both primary and secondary CVD prevention settings.

Materials And Methods: Bayesian joint modelling of repeated measures of eGFR and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to examine the association between the eGFR slope and the incidence of major adverse CV event/hospitalization for heart failure (MACE/hHF) (non-fatal myocardial infarction, non-fatal stroke, CV death, or hospitalization for heart failure).

Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91).

Background: The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years.

Comparison of medical resources and costs among patients with coronary heart disease and impaired glucose tolerance in the Acarbose Cardiovascular Evaluation trial.

Background: The Acarbose Cardiovascular Evaluation (ACE) trial (ISRCTN91899513) evaluated the alpha-glucosidase inhibitor acarbose, compared with placebo, in 6522 patients with coronary heart disease and impaired glucose tolerance in China and showed a reduced incidence of diabetes. We assessed the within-trial medical resource use and costs, and quality-adjusted life years (QALYs).

Methods: Resource use data were collected prospectively within the ACE trial.

Orthostatic Hypotension, Hypertension Treatment, and Cardiovascular Disease: An Individual Participant Meta-Analysis.

Importance: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension.

Objective: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension.

Data Sources: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022.

Gamified Problem Gambling and Psychological Distress: The Mediated-Moderated Roles of Cognitive and Economic Motives.

Economic and non-economic motives for gambling may amplify anxiety and depression among young adults. On the grounds that online gambling is highly addictive, it is imperative to assess significant contributory factors in gambling that aggravate financial harm and psychological distress. The study examines gamified problem gambling and psychological distress among young adults in Ghanaian universities.

Bubble-PAPR: a phase 1 clinical evaluation of the comfort and perception of a prototype powered air-purifying respirator for use by healthcare workers in an acute hospital setting.

Objectives: We aimed to design and produce a low-cost, ergonomic, hood-integrated powered air-purifying respirator (Bubble-PAPR) for pandemic healthcare use, offering optimal and equitable protection to all staff. We hypothesised that participants would rate Bubble-PAPR more highly than current filtering face piece (FFP3) face mask respiratory protective equipment (RPE) in the domains of comfort, perceived safety and communication.

Design: Rapid design and evaluation cycles occurred based on the identified user needs.

Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin: The Randomized, Controlled EMPA-VISION Trial.

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production.

11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial.

Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid, we investigated whether 11β-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810).

Joint longitudinal and time-to-event modelling compared with standard Cox modelling in patients with type 2 diabetes with and without established cardiovascular disease: An analysis of the EXSCEL trial.

Aim: To demonstrate the gain in predictive performance when cardiovascular disease (CVD) risk prediction tools (RPTs) incorporate repeated rather than only single measurements of risk factors.

Materials And Methods: We used data from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to compare the quality of predictions of future major adverse cardiovascular events (MACE) with the Cox proportional hazards model (using single values of risk factors) compared to the Bayesian joint model (using repeated measures of risk factors). The risk of MACE was calculated in patients with type 2 diabetes with and without established CVD.

Risk prediction models for incident type 2 diabetes in Chinese people with intermediate hyperglycemia: a systematic literature review and external validation study.

Background: People with intermediate hyperglycemia (IH), including impaired fasting glucose and/or impaired glucose tolerance, are at higher risk of developing type 2 diabetes (T2D) than those with normoglycemia. We aimed to evaluate the performance of published T2D risk prediction models in Chinese people with IH to inform them about the choice of primary diabetes prevention measures.

Methods: A systematic literature search was conducted to identify Asian-derived T2D risk prediction models, which were eligible if they were built on a prospective cohort of Asian adults without diabetes at baseline and utilized routinely-available variables to predict future risk of T2D.

Historical HbA Values May Explain the Type 2 Diabetes Legacy Effect: UKPDS 88.

Objective: Type 2 diabetes all-cause mortality (ACM) and myocardial infarction (MI) glycemic legacy effects have not been explained. We examined their relationships with prior individual HbA values and explored the potential impact of instituting earlier, compared with delayed, glucose-lowering therapy.

Research Design And Methods: Twenty-year ACM and MI hazard functions were estimated from diagnosis of type 2 diabetes in 3,802 UK Prospective Diabetes Study participants.

Increased Risk of Incident Heart Failure and Death Is Associated With Insulin Resistance in People With Newly Diagnosed Type 2 Diabetes: UKPDS 89.

Objective: Insulin resistance (IR) may mediate heart failure (HF) development. We examined whether IR in people with newly diagnosed type 2 diabetes (T2D) increased their risk of a composite outcome of HF or death or of HF alone.

Research Design And Methods: Insulin resistance (HOMA2-IR) values for UKPDS participants were derived from paired fasting plasma glucose (FPG) and insulin measures.

Design and rationale of the EMPA-VISION trial: investigating the metabolic effects of empagliflozin in patients with heart failure.

Aims: Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium-glucose co-transporter-2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR-Reduced trial and cardiovascular mortality in the EMPA-REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR).

Predicting the risk of developing type 2 diabetes in Chinese people who have coronary heart disease and impaired glucose tolerance.

Aims: Robust diabetes risk estimates in Asian patients with impaired glucose tolerance (IGT) and coronary heart disease (CHD) are lacking. We developed a Chinese type 2 diabetes risk calculator using Acarbose Cardiovascular Evaluation (ACE) trial data.

Methods: There were 3105 placebo-treated ACE participants with requisite data for model development.

Refeeding risks in patients requiring intravenous nutrition support: Results of a two-centre, prospective, double-blind, randomised controlled trial.

Background/aims: Refeeding syndrome can result following excessive feeding of malnourished patients. The syndrome remains poorly defined but encompasses a range of adverse effects including electrolyte shifts, hyperglycaemia and other less well-defined phenomena. There are additional risks of underfeeding malnourished individuals.

Predicting heart failure events in patients with coronary heart disease and impaired glucose tolerance: Insights from the Acarbose Cardiovascular Evaluation (ACE) trial.

Aims: Heart failure is a fatal complication of type 2 diabetes but little is known about its incidence in people with impaired glucose tolerance (IGT). We used Acarbose Cardiovascular Evaluation (ACE) trial data to identify predictors of hospitalisation for heart failure (hHF) or cardiovascular (CV) death in patients with coronary heart disease (CHD) and IGT randomised to acarbose or placebo.

Methods: Independent hHF/CV death risk factors were determined using Cox proportional hazards models, with participants censored at first hHF event, CV death, or end of follow-up.