Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction-associated steatotic liver disease but is not altered by 6 weeks of exercise training.

Aims: To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction-associated steatotic liver disease (MASLD).

Materials And Methods: In Part A (cross-sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol [<6.

Effectiveness of integrating a pragmatic pathway for prescribing liraglutide 3.0 mg in weight management services (STRIVE study): a multicentre, open-label, parallel-group, randomized controlled trial.

Background: An effective prescribing pathway for liraglutide 3 mg, an approved obesity pharmacotherapy, may improve treatment access. This trial compared a targeted prescribing pathway for liraglutide 3 mg with multiple stopping rules in specialist weight management services (SWMS) to standard SWMS care.

Methods: This phase four, two-year, multicentre, open-label, parallel-group, real-world randomized clinical trial (ClinicalTrials.

Effect of delay in treatment intensification in people with type 2 diabetes and suboptimal glycaemia after basal insulin initiation: A real-world observational study.

Aim: Despite global recommendations for type 2 diabetes mellitus treatment to maintain optimal glycaemic targets, a significant proportion of people remain in suboptimal glycaemic control. Our objective was to investigate the impact of intensification delay after basal insulin (BI) initiation on long-term complications in people with suboptimal glycaemia.

Materials And Methods: We conducted a retrospective cohort study in individuals with type 2 diabetes mellitus initiated on BI.

Factors associated with therapeutic inertia in individuals with type 2 diabetes mellitus started on basal insulin.

Aim: In this study we aim to identify the factors associated with treatment inertia in patients with type 2 diabetes mellitus (T2DM) who have been recently started on basal insulin (BI).

Methods: Using UK CPRD GOLD, we identified adults with T2DM with suboptimal glycaemia (HbA1c within 12 months of BI ≥ 7% (≥53 mmol/mol)). We used multivariable Cox regression model to describe the association between patient characteristics and the time to treatment intensification.

Impact of novel glucose-lowering therapies on physical function in people with type 2 diabetes: A systematic review and meta-analysis of randomised placebo-controlled trials.

Aims: We investigated evidence from randomised, placebo-controlled trials of novel glucose-lowering therapies; sodium-glucose co-transporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), on physical function in people with type 2 diabetes (T2D).

Methods: PubMed, Medline, Embase and Cochrane library were searched from 1 April 2005 to 20 January 2022. The primary outcome was change in physical function in groups receiving a novel glucose-lowering therapy versus placebo at the trial end-point.

The effects of weight-lowering pharmacotherapies on physical activity, function and fitness: A systematic review and meta-analysis of randomized controlled trials.

Weight-lowering pharmacotherapies provide an option for weight management; however, their effects on physical activity, function, and cardiorespiratory fitness are not fully understood. We conducted a systematic review and meta-analysis of randomized controlled trials to investigate the effect of licensed weight loss pharmacotherapies on physical activity, physical function, and cardiorespiratory fitness in individuals with obesity. Fourteen trials met our prespecified inclusion criteria: Five investigated liraglutide, four semaglutide, three naltrexone/bupropion, and two phentermine/topiramate.

The effect of acute and chronic exercise on hepatic lipid composition.

Exercise is recommended for those with, or at risk of nonalcoholic fatty liver disease (NAFLD), owing to beneficial effects on hepatic steatosis and cardiometabolic risk. Whilst exercise training reduces total intrahepatic lipid in people with NAFLD, accumulating evidence indicates that exercise may also modulate hepatic lipid composition. This metabolic influence is important as the profile of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) dramatically affect the metabolic consequences of hepatic lipid accumulation; with SFA being especially lipotoxic.

Type 2 diabetes.

Type 2 diabetes accounts for nearly 90% of the approximately 537 million cases of diabetes worldwide. The number affected is increasing rapidly with alarming trends in children and young adults (up to age 40 years). Early detection and proactive management are crucial for prevention and mitigation of microvascular and macrovascular complications and mortality burden.

The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: The SEESAW randomized, double-blind, placebo-controlled trial.

Aim: To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity.

Materials And Methods: In a double-blind, placebo-controlled trial, 68 adults (aged 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%-10.

Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile: A pooled analysis.

Background: The diagnosis of type 2 diabetes (T2D) in younger adults, an increasingly common public health issue, is associated with a higher risk of cardiovascular complications and mortality, which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.

Aim: To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.

Methods: A pooled dataset was used, comprised of data from five previous studies of adults with T2D, including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.

Consultation rates in people with type 2 diabetes with and without vascular complications: a retrospective analysis of 141,328 adults in England.

Objective: To assess trends in primary and specialist care consultation rates and average length of consultation by cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), or cardiometabolic multimorbidity exposure status.

Methods: Observational, retrospective cohort study used linked Clinical Practice Research Datalink primary care data from 01/01/2000 to 31/12/2018 to assess consultation rates in 141,328 adults with newly diagnosed T2DM, with or without CVD. Patients who entered the study with either a diagnosis of T2DM or CVD and later developed the second condition during the study are classified as the cardiometabolic multimorbidity group.

Clinical associations with stage B heart failure in adults with type 2 diabetes.

Background: There is a high prevalence of asymptomatic (American Heart Association Stage B) heart failure (SBHF) in people with type 2 diabetes (T2D). We aimed to identify associations between clinical characteristics and markers of SBHF in adults with T2D, which may allow therapeutic interventions prior to symptom onset.

Methods: Adults with T2D from a multi-ethnic population with no prevalent cardiovascular disease [ = 247, age 52 ± 12 years, glycated haemoglobin A1c (HbA1c) 7.

Animal models for SARS-Cov2/Covid19 research-A commentary.

There is an urgent need for new animal models of SARS CoV-2 infection to improve research and drug development. This brief commentary examines the deficits of current models and proposes several improved alternates. The existing single transgene mouse models poorly mimic the clinical features of COVID-19; those strains get a milder disease than human COVID-19 disease.

Effect of metformin on biomarkers of placental- mediated disease: A systematic review and meta-analysis.

Metformin reduces the incidence of placental-mediated disease (PMD) in pregnancies with and without diabetes, but the mechanism through which it exerts these effects is not yet fully understood. We performed a systematic review and meta-analysis to examine the effect of metformin on biomarkers implicated in the pathogenesis of PMD. We searched Medline, Embase and the Cochrane Library for studies of metformin and biomarkers of PMD in pregnancy.

Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial.

The mechanisms behind the beneficial cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared with dipeptidyl peptidase-4 inhibitors (DPP4is) remain largely unknown, despite both targeting the incretin pathway to improve glycaemic control. In these prespecified secondary analyses of the LYDIA trial, we examined the impact of the GLP-1RA liraglutide (1.8 mg once-daily) and the DPP4i sitagliptin (100 mg once-daily) on circulating cardiovascular biomarkers associated with atherosclerotic risk, including circulating progenitor cells (CPCs).

Association of weight loss and weight loss maintenance following diabetes diagnosis by screening and incidence of cardiovascular disease and all-cause mortality: An observational analysis of the ADDITION-Europe trial.

Aims: Short-term weight loss may lead to remission of type 2 diabetes but the effect of maintained weight loss on cardiovascular disease (CVD) is unknown. We quantified the associations between changes in weight 5 years following a diagnosis of diabetes, and incident CVD events and mortality up to 10 years after diagnosis.

Materials And Methods: Observational analysis of the ADDITION-Europe trial of 2730 adults with screen-detected type 2 diabetes from the UK, Denmark and the Netherlands.

Where Does Metformin Stand in Modern Day Management of Type 2 Diabetes?

Metformin is the most commonly used glucose-lowering therapy (GLT) worldwide and remains the first-line therapy for newly diagnosed individuals with type 2 diabetes (T2D) in management algorithms and guidelines after the UK Prospective Diabetes Study (UKPDS) showed cardiovascular mortality benefits in the overweight population using metformin. However, the improved Major Adverse Cardiovascular Events (MACE) realised in some of the recent large cardiovascular outcomes trials (CVOTs) using sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have challenged metformin's position as a first-line agent in the management of T2D. Many experts now advocate revising the existing treatment algorithms to target atherosclerotic cardiovascular disease (ASCVD) and improving glycaemic control as a secondary aim.

Improvements in Glycemic Control After Acute Moderate-Intensity Continuous or High-Intensity Interval Exercise Are Greater in South Asians Than White Europeans With Nondiabetic Hyperglycemia: A Randomized Crossover Study.

Objective: To examine whether circulating metabolic responses to low-volume high-intensity interval exercise (LV-HIIE) or continuous moderate-intensity aerobic exercise (CME) differ between white Europeans and South Asians with nondiabetic hyperglycemia (NDH).

Research Design And Methods: Thirteen white Europeans and 10 South Asians (combined median [interquartile range] age 67 [60-68] years, HbA 5.9% [5.

Adults with early-onset type 2 diabetes (aged 18-39 years) are severely underrepresented in diabetes clinical research trials.

Aims/hypothesis: Early-onset adult type 2 diabetes (diagnosed between ages 18 and 39 years) is increasingly prevalent and associated with poor long-term outcomes. We hypothesised that individuals with early-onset adult type 2 diabetes were underrepresented in the prominent research trials that underpin type 2 diabetes management guidelines.

Methods: We reviewed the mean age of the study populations recruited to 90 prominent trials in type 2 diabetes, including 37 cardio-renal outcomes trials across a range of pharmacological, non-pharmacological and multifactorial interventions, 28 trials from the phase III programmes of three representative glucose-lowering therapies used routinely in clinical practice (empagliflozin, liraglutide and sitagliptin) and 25 prominent trials of diabetes self-management education and support or intensive lifestyle interventions (diet or supervised exercise training).

Number needed to treat in cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists: A systematic review with temporal analysis.

Cardiovascular outcome trials (CVOTs) investigating the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have highlighted some important differences among these medications. The recent American Diabetes Association and European Association for the Study of Diabetes consensus underlines that each trial constitutes a single experiment; therefore, it remains unclear if, and to what extent, the observed differences reflect the heterogeneous pharmacological properties of each compound. To help clarify the evidence, in this systematic review we investigated differences in trial characteristics which may have had an impact on the primary and secondary trial results, including baseline control of risk factors, prevalence of cardiovascular diseases, absolute rates of events, duration of the study, and definitions of the inclusion criteria and outcomes.