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Aim: Existing data on the association between blood pressure levels and adverse cardiovascular outcomes in patients with heart failure (HF) are inconsistent. The optimal blood pressure targets for patients with HF remain uncertain. This study sought to assess the associations between blood pressure (systolic [SBP] and diastolic blood pressure [DBP]) levels and adverse cardiovascular disease (CVD) outcomes in patients with HF. Methods and results: A systematic review and meta‐analysis were conducted using MEDLINE, Embase, the Cochrane Library, and Web of Science databases up to 5 May 2023. The outcomes of interest included adverse cardiovascular events and all‐cause mortality. Pooled relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Forty‐three unique observational cohort studies, comprising 120 643 participants with HF, were included. The pooled RRs (95% CIs) for SBP thresholds of ≥140 mmHg versus <140 mmHg were 0.92 (0.83–1.01) for all‐cause mortality, 0.83 (0.67–1.04) for CVD death, and 0.98 (0.80–1.21) for HF hospitalization. The pooled RR (95% CI) for SBP thresholds of ≥160 mmHg versus <160 mmHg and all‐cause mortality was 0.67 (0.62–0.74). SBP levels below <130, <120, and <110 mmHg were each associated with an increased risk of various cardiovascular endpoints and all‐cause mortality. The pooled RR (95% CI) for DBP thresholds of ≥80 mmHg versus <80 mmHg and all‐cause mortality was 0.86 (0.67–1.10). A 10 mmHg increase in SBP or DBP was associated with a reduction in all‐cause mortality and other cardiovascular endpoints. Conclusions: The findings suggest that lower and normal baseline SBP levels (<130, <120, and <110 mmHg) may be associated with future risk of worse outcomes in patients with HF. Optimal baseline blood pressure levels for these patients may lie within the range of ≥140 mmHg for SBP. In the absence of observational studies with repeated blood pressure measurements or definitive trials evaluating optimal blood pressure targets, individualized blood pressure targets based on patients' unique circumstances are warranted in HF management. [ABSTRACT FROM AUTHOR]

A substantial evidence base supports the use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in the treatment of type 2 diabetes mellitus (T2DM). This class of medicines has demonstrated important benefits that extend beyond glucose-lowering efficacy to protective mechanisms capable of slowing or preventing the onset of long-term cardiovascular, renal and metabolic (CVRM) complications, making their use highly applicable for organ protection and the maintenance of long-term health outcomes. SGLT2is have shown cost-effectiveness in T2DM management and economic savings over other glucose-lowering therapies due to reduced incidence of cardiovascular and renal events. National and international guidelines advocate SGLT2i use early in the T2DM management pathway, based upon a plethora of supporting data from large-scale cardiovascular outcome trials, renal outcomes trials and real-world studies. While most people with T2DM would benefit from CVRM protection through SGLT2i use, prescribing hesitancy remains, potentially due to confusion concerning their place in the complex therapeutic paradigm, variation in licensed indications or safety perceptions/misunderstandings associated with historical data that have since been superseded by robust clinical evidence and long-term pharmacovigilance reporting. This latest narrative review developed by the Improving Diabetes Steering Committee (IDSC) outlines the place of SGLT2is within current evidence-informed guidelines, examines their potential as the standard of care for the majority of newly diagnosed people with T2DM and sets into context the perceived risks and proven advantages of SGLT2is in terms of sustained health outcomes. The authors discuss the cost-effectiveness case for SGLT2is and provide user-friendly tools to support healthcare professionals in the correct application of these medicines in T2DM management. The previously published IDSC SGLT2i Prescribing Tool for T2DM Management has undergone updates and reformatting and is now available as a Decision Tool in an interactive pdf format as well as an abbreviated printable A4 poster/wall chart. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes is a widespread health concern with significant implications for patient well-being. Poor glycaemic control can lead to long-term complications, hypoglycaemia and glycaemic variability, highlighting the importance of setting treatment goals. This podcast, "The use of CGM in optimizing type 2 diabetes management with non-intensive insulin treatment in the primary care setting", introduces non-intensive insulin treatment and continuous glucose monitoring (CGM) as crucial tools in achieving these goals. Objectives and Rationale: The advantages of CGM over blood glucose monitoring (BGM) are explored, emphasizing its real-time glucose data provision and how it empowers patients to make informed treatment decisions. Drawing on randomized controlled trials (RCTs), the compelling evidence of CGM's effectiveness in patients with type 2 diabetes on basal insulin treatment are discussed. Additionally, the real-world evidence, comparing outcomes between insulin-treated and non-insulin-treated patients are also addressed. The podcast examines the link between glycaemic control and acute complications requiring hospitalizations and how CGM contributes to a better quality of life for patients with type 2 diabetes. Empowering patients is central to this podcast, with a focus on education, engagement and strategies for integrating CGM data into treatment plans. The pivotal role of healthcare providers in supporting patients on non-intensive insulin treatment and CGM in the primary care setting is addressed. Addressing challenges and barriers in CGM adoption, including cost considerations, technology accessibility and patient concerns, is vital to its widespread use. There is also a consideration of the cost-effectiveness of CGM in type 2 diabetes management. The podcast provides insights into when to consider CGM, including intermittent use and data integration with other health technologies. It emphasizes the potential for improved patient outcomes and a reduced burden of type 2 diabetes. Practical tips for interpreting the Ambulatory Glucose Profile (AGP) report are shared, benefitting primary care healthcare professionals new to CGM. Conclusion: The podcast "The use of CGM in optimizing type 2 diabetes management with non-intensive insulin treatment in the primary care setting" highlights the transformative potential of CGM in type 2 diabetes care. It encourages patients and healthcare providers to consider CGM as an integral part of treatment plans, ultimately improving the lives of those living with type 2 diabetes. 28JAp7R3q_BT3_eGo-rbWB Podcast Video (MP4 261831 KB) [ABSTRACT FROM AUTHOR]

BACKGROUND: Traditional diabetes self-monitoring of blood glucose (SMBG) involves inconvenient finger pricks. Continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems offer CGM, enhancing type 2 diabetes (T2D) management with convenient, comprehensive data. PURPOSE: To assess the benefits and potential harms of CGM and isCGM compared with usual care or SMBG in individuals with T2D. DATA SOURCES: We conducted a comprehensive search of MEDLINE, Embase, the Cochrane Library, Web of Science, and bibliographies up to August 2023. STUDY SELECTION: We analyzed studies meeting these criteria: randomized controlled trials (RCT) with comparison of at least two interventions for ≥8 weeks in T2D patients, including CGM in real-time/retrospective mode, short-/long-term CGM, isCGM, and SMBG, reporting glycemic and relevant data. DATA EXTRACTION: We used a standardized data collection form, extracting details including author, year, study design, baseline characteristics, intervention, and outcomes. DATA SYNTHESIS: We included 26 RCTs (17 CGM and 9 isCGM) involving 2,783 patients with T2D (CGM 632 vs. usual care/SMBG 514 and isCGM 871 vs. usual care/SMBG 766). CGM reduced HbA1c (mean difference −0.19% [95% CI −0.34, −0.04]) and glycemic medication effect score (−0.67 [−1.20 to −0.13]), reduced user satisfaction (−0.54 [−0.98, −0.11]), and increased the risk of adverse events (relative risk [RR] 1.22 [95% CI 1.01, 1.47]). isCGM reduced HbA1c by −0.31% (−0.46, −0.17), increased user satisfaction (0.44 [0.29, 0.59]), improved CGM metrics, and increased the risk of adverse events (RR 1.30 [0.05, 1.62]). Neither CGM nor isCGM had a significant impact on body composition, blood pressure, or lipid levels. LIMITATIONS: Limitations include small samples, single-study outcomes, population variations, and uncertainty for younger adults. Additionally, inclusion of <10 studies for most end points restricted comprehensive analysis, and technological advancements over time need to be considered. CONCLUSIONS: Both CGM and isCGM demonstrated a reduction in HbA1c levels in individuals with T2D, and unlike CGM, isCGM use was associated with improved user satisfaction. The impact of these devices on body composition, blood pressure, and lipid levels remains unclear, while both CGM and isCGM use were associated with increased risk of adverse events. [ABSTRACT FROM AUTHOR]

Objective. Temporal trends in admissions for atrial fibrillation (AF) and severe bleeding associated with AF vary worldwide. We aimed to explore their temporal trends in England and their relation to the introduction of DOACs in 2014 in the UK. Design. This longitudinal ecological study utilised aggregated data that was extracted from the Hospital Episode Statistics database, which captured annual admissions for AF and severe bleeding associated with AF between 2001 and 2018. Trends in admissions over the study period and across age groups, gender and regions in England were assessed. Results. In total, there were 11,292,177 admissions for AF and 324,851 admissions for severe bleeding associated with AF. There was a steady rise in admissions for AF from 2001 to 2017 (204,808 to 1,109,295; p for trend<.001). A similar trend was observed for severe bleeding (4940 to 30,169; p for trend <.001), but the increase dropped slightly between 2013 and 2014 and continued thereafter. Conclusions. There was a rise in admissions for AF and severe bleeding in England between 2001 and 2018. There is little evidence that the slight drop in admissions for severe bleeding between 2013 and 2014 may have been caused by the introduction of DOACs in 2014. Contributors to these trends need urgent exploration. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of the initial combination therapy versus a stepwise approach in newly diagnosed type 2 diabetes (T2D) by conducting a systematic review and meta‐analysis of observational cohort studies and randomized controlled trials (RCTs). Methods: Studies were identified from MEDLINE, Embase, the Cochrane Library, and through search of bibliographies to January 2022. Study‐specific risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: Eight articles including four unique RCTs (n = 5527 participants) and one observational cohort study (n = 200) that compared initial combination therapy versus stepwise therapy were included. The RR for myocardial infarction comparing initial combination therapy versus stepwise therapy was 1.21 (95% CI 0.74‐2.00). Initial combination therapy reduced levels of fasting plasma glucose and glycated haemoglobin: mean differences −0.97 mmol/L (95% CI −1.41, −0.53) and −24.92 mmol/mol (95% CI −25.67, −24.27), respectively. Initial combination therapy versus stepwise therapy reduced lipid levels, blood pressure and intima media thickness, with no differences in body composition variables, neuropathy, retinopathy or adverse events. Single‐study results showed that initial combination therapy reduced creatinine levels and urine albumin excretion rate. The quality of the evidence ranged from moderate to very low. Conclusions: Except for improving cardiometabolic and glycaemic variables, a limited number of studies characterized by small sample sizes show that initial combination therapy for newly diagnosed T2D may be similar in efficacy and safety to stepwise therapy with respect to cardio‐renal outcomes. There is a lack of sufficient evidence to recommend initial combination therapy with glucose‐lowering agents in newly diagnosed T2D with the aim of preventing cardio‐renal outcomes. Definitive RCTs are warranted. [ABSTRACT FROM AUTHOR]

Objectives. A general body of evidence suggests that low serum albumin might be associated with increased risk of adverse cardiometabolic outcomes, but findings are divergent. We aimed to quantify associations of serum albumin with the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), all-cause mortality, and other adverse outcomes using a systematic review and meta-analyses of published observational cohort studies. Design. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched to January 2020. Relative risks (RRs) with 95% confidence intervals (CIs) comparing top versus bottom thirds of serum albumin levels were pooled. Results. Fifty-four articles based on 48 unique observational cohort studies comprising of 1,492,237 participants were eligible. Multivariable adjusted RRs (95% CIs) comparing the top vs bottom third of serum albumin levels were: 1.03 (0.86–1.22) for T2D; 0.60 (0.53–0.67) for CVD; 0.74 (0.66–0.84) for coronary heart disease (CHD); 0.57 (0.36–0.91) for CHD death; 0.76 (0.65–0.87) for myocardial infarction; 0.66 (0.55–0.77) for all-cause mortality; 0.71 (0.61–0.83) for venous thromboembolism; 0.65 (0.48–0.88) for cancer mortality; and 0.62 (0.46–0.84) for fracture. Heterogeneity between contributing studies of T2D was partly explained by sample sizes of studies (p for meta-regression =.035). Conclusions. Elevated levels of serum albumin are associated with reduced risk of vascular outcomes, all-cause mortality, certain cancers, and fracture. Inconsistent findings for T2D may be attributed to selective reporting by studies. Further research is needed to assess any potential causal relevance to these findings and the role of serum albumin concentrations in disease prevention. Systematic review registration: PROSPERO 2019: CRD42019125869 [ABSTRACT FROM AUTHOR]

Objectives. Circulating osteocalcin (OC), a marker which is central in bone mineralization, may be involved in the atherosclerotic process and influence the risk of developing cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of published observational evidence, to assess and quantify the associations of circulating OC (total, undercarboxylated, and carboxylated OC) with cardiovascular outcomes (clinical CVD endpoints and intermediate cardiovascular phenotypes).Design. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and reference lists of relevant studies to March 2019. Mean differences and risk ratios with 95% CIs were aggregated using random-effects models.Results. Thirty-three observational studies (prospective and retrospective cohort, case-control, and cross-sectional) with data on 21,021 unique participants were eligible. The pooled risk ratio in a comparison of extreme fourths of total OC levels was 0.98 (95% CI 0.89, 1.08) for composite CVD. Circulating total OC levels were significantly lower in patients with cardiovascular conditions compared with those without these conditions -2.58 ng/ml (95% CI -3.85, -1.32; p < .001). Prospective and cross-sectional data showed significant inverse associations between total OC and traits such as aortic or coronary calcification, coronary atherosclerosis or calcification, carotid intima-media thickness, and plaque score. There was limited data on carboxylated and undercarboxylated OC, with no evidence of associations.Conclusion. Observational evidence generally supports inverse associations of circulating total OC with risk of atherosclerotic outcomes and CVD endpoints; however, the data were mostly based on cross-sectional evaluations. Large-scale prospective data are needed. [ABSTRACT FROM AUTHOR]

Aim: To assess deintensification approaches and rates and evaluate the harm and benefits of deintensification with antidiabetic medication and other therapies among older people (≥ 65 years) with type 2 diabetes with or without cardiometabolic conditions. Methods: We identified relevant studies in a literature search of MEDLINE, Embase, Web of Science and Cochrane databases to 30 October 2018. Data were extracted on baseline characteristics, details on deintensification and outcomes, and was synthesized using a narrative approach. Results: Ten studies (observational cohorts and interventional studies) with data on 26 558 patients with comorbidities were eligible. Deintensification approaches included complete withdrawal, discontinuation, reducing dosage, conversion, or substitution of at least one medication, but the majority of studies were based on complete withdrawal or discontinuation of antihyperglycaemic medication. Rates of deintensification approaches ranged from 13.4%–75%. The majority of studies reported no deterioration in HbA1c levels, hypoglycaemic episodes, falls or hospitalizations on deintensification. On adverse events and mortality, no significant differences were observed among the comparison groups in the majority of studies. Conclusion: Available but limited evidence suggests that the benefits of deintensification outweigh the harm in older people with type 2 diabetes with or without comorbidities. Given the heterogeneity of patients with diabetes, further research is warranted on which deintensification approaches are appropriate and beneficial for each specific patient population. [ABSTRACT FROM AUTHOR]

Objective: A previous study suggests an association between poor medication adherence and excess mortality in chronic disease. The purpose of this study was to assess the association between medication adherence and risk of cardiovascular disease (CVD), all-cause mortality, and hospitalization in type 2 diabetes.Research Design and Methods: We conducted an electronic search on many electronic databases from inception to 27 April 2016. We selected randomized controlled trials and case-control and cohort studies reporting on CVD, all-cause mortality, or hospitalization outcomes by adherence in adults with type 2 diabetes. Two reviewers independently screened for eligible studies and extracted outcome data. Pooled relative risks (RRs) were calculated using a random-effects meta-analysis; risk of bias in each of the included studies was assessed using the GRADE approach.Results: Eight observational studies were included (n = 318,125). The mean rate of poor adherence was 37.8% (95% CI 37.6-38.0). Adjusted estimates were provided by five studies only. The RRs of good (≥80%) versus poor adherence to medication were 0.72 (95% CI 0.62-0.82, I2 = 0%, three studies) for all-cause mortality and 0.90 (0.87-0.94, I2 = 63%, seven studies) for hospitalization. No evidence of small study bias was observed. Only one study reported CVD outcomes by adherence.Conclusions: We identified no trials reporting on outcomes by adherence, suggesting a systematic failure to include this information. Pooled estimates from available observational studies suggest that good medication adherence is associated with reduced risk of all-cause mortality and hospitalization in people with type 2 diabetes, although bias cannot be excluded as an explanation for these findings. [ABSTRACT FROM AUTHOR]

The article offers information on a study related to therapeutic inertia and the legacy of dysglycemia on microvascular and macrovascular complications of diabetes. It notes that type 2 diabetes is characterized by a continuous decline in b-cell function with resultant progressive loss of glycemic control over time. It is mentioned that this study explore the need to intensify blood glucose-lowering therapy to ensure that the benefits of reduced blood glucose are realized.

The article discusses the authors' views about whether sodium-glucose co-transporter-2 inhibitors should be used as a first-line oral therapy for type 2 diabetes patients, and it mentions the individualization of therapies to manage hyperglycaemia. Metformin therapy for diabetics is addressed, along with information obtained from the British UK Prospective Diabetes Study (UKPDS). Microvascular and macrovascular complications from diabetes are assessed.

Introduction Approximately 366 million people worldwide live with diabetes and this figure is expected to rise. Among the correct diagnosis, there will be errors in the diagnosis, classification and coding, resulting in adverse health and financial implications. Aim To determine the prevalence and characteristics of diagnostic errors in people with diabetes managed in primary care settings. Methods We conducted a cross-sectional study in nine general practices in Leicester, UK, from May to August 2011, using a validated electronic toolkit. Searches identified cases with potential errors which were manually checked for accuracy. Results There were 54 088 patients and 2434 (4.5%) diagnosed with diabetes. Out of 316 people identified with potential errors with the toolkit, 180 (57%) had confirmed errors after manually reviewing the records, resulting in an error prevalence of 7.4%. Correctly coded people on registers had significantly greater glycated haemoglobin (HbA1c) reductions. There were no significant differences between patients with and without errors in their HbA1C, body mass index, age and size of practice. There was also no significant association of the errors with pay-for-performance initiatives; however, those patients not on disease register had worse glycaemic control. Conclusions A high prevalence of diabetic diagnostic errors was confirmed using medication, biochemical and demographic data. Larger studies are needed to more accurately assess the scale of this problem. Automation of these processes might be possible, which would allow searches to be even more user friendly. [ABSTRACT FROM AUTHOR]

Aim: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose‐lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. Materials and Methods: In this systematic review and meta‐analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study‐specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta‐regression was employed to analyse the relationships between outcomes and HbA1c reduction. Results: We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non‐fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75‐0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92‐1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78‐0.93), nephropathy (HR 0.71; 0.58‐0.87) and composite microvascular outcomes (HR 0.88; 0.77‐1.00). Meta‐regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non‐fatal MI, stroke and retinopathy, but these were not statistically significant. Conclusions: In people with T2D, intensive glucose control was associated with a reduced risk of non‐fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose‐lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control. [ABSTRACT FROM AUTHOR]

Aim: Using a systematic review and meta‐analysis of placebo‐controlled cardiovascular outcome trials (CVOTs) of newer glucose‐lowering agents [sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is), glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), and dipeptidyl peptidase‐4 inhibitors (DPP‐4is)] in type 2 diabetes (T2D), we aimed to determine the macrovascular and microvascular outcomes of these agents and clarify the relationships between glycated haemoglobin (HbA1c) reduction and risk of these outcomes. Materials and Methods: Randomized controlled trials were identified from MEDLINE, Embase and the Cochrane Library until September 2023. Study‐specific hazard ratios with 95% confidence intervals (CIs) were pooled, and meta‐regression was used to assess the relationships between outcomes and between trial arm HbA1c reductions. Results: Twenty unique CVOTs (six SGLT‐2is, nine GLP‐1RAs, five DPP‐4is), based on 169 513 participants with T2D, were eligible. Comparing SGLT‐2is, GLP‐1RAs and DPP‐4is with placebo, the hazard ratios (95% CIs) for 3‐point major adverse cardiovascular events were 0.88 (0.82‐0.94), 0.85 (0.79‐0.92) and 1.00 (0.94‐1.06), respectively. SGLT‐2is and GLP‐1RAs consistently reduced the risk of several macrovascular and microvascular complications, particularly kidney events. DPP‐4is showed no macrovascular benefits. There was potential evidence of an inverse linear relationship between HbA1c reduction and 3‐point major adverse cardiovascular event risk (estimated risk per 1% reduction in HbA1c: 0.84, 95% CI 0.67‐1.06; p =.14; R2 = 14.2%), which was driven by the component of non‐fatal stroke (R2 = 100.0%; p =.094). There were non‐significant inverse linear relationships between HbA1c reduction and the risk of several vascular outcomes. Conclusions: SGLT‐2is and GLP‐1RAs showed consistent risk reductions in macrovascular and microvascular outcomes. The vascular benefits of SGLT‐2is and GLP‐1RAs in patients with T2D extend beyond mere glycaemic control. [ABSTRACT FROM AUTHOR]

Although continuous glucose monitoring (CGM) devices are now considered the standard of care for people with type 1 diabetes mellitus, the uptake among people with type 2 diabetes mellitus (T2DM) has been slower and is focused on those receiving intensive insulin therapy. However, increasing evidence now supports the inclusion of CGM in the routine care of people with T2DM who are on basal insulin-only regimens or are managed with other medications. Expanding CGM to these groups could minimize hypoglycaemia while allowing efficient adaptation and escalation of therapies. Increasing evidence from randomized controlled trials and observational studies indicates that CGM is of clinical value in people with T2DM on non-intensive treatment regimens. If further studies confirm this finding, CGM could soon become a part of routine care for T2DM. In this Perspective we explore the potential benefits of widening the application of CGM in T2DM, along with the challenges that must be overcome for the evidence-based benefits of this technology to be delivered for all people with T2DM. Continuous glucose monitoring (CGM) is an effective tool in the management of diabetes mellitus. This Perspective discusses the potential benefits of widespread adoption of CGM in people with type 2 diabetes mellitus at different stages of disease progression and treatment intensification. [ABSTRACT FROM AUTHOR]

Using the Clinical Practice Research Datalink, adults diagnosed with T2DM newly initiated with a basal long/intermediate-acting insulin from January 2004 to December 2016 were identified. First change or add on of short or premix insulin and/or OADs was defined as intensification. Patients were categorized into three groups; uncontrolled glycaemia at baseline (≥7% HbA1c) and early (within 1-year) intensifiers, and uncontrolled glycaemia at baseline and delayed (>1-year) intensifiers and uncontrolled-non-intensifiers as a reference groups. A total of n=8,538 patients were included; 32.95% (n=2,813) were uncontrolled-glycaemic-early intensifiers, 28.91% (n=2,468) were uncontrolled glycaemic-delayed intensifiers, and 38.15% (n=3,257) were non-intensifiers. Majority of the early and delayed intensified patients were males (54.60% and 57.41% respectively) and the average age was 62.40years. Non-intensifiers were older (67.72 years) and had a greater number of risk factors. Median baseline HbA1c was 85.90mmol/mol [10.01%] (IQR, 73.9-101.0 mmol/mol; 8.91-11.39%) and 82.50mmol/mol [9.70%] (IQR, 71.60-96.70mmol/mol, 8.70-11.00%) in the early and delayed treatment intensified group respectively. Early treatment intensification within 1-year post basal insulin therapy was linked to 18% (HR CI: 0.65, 1.03), 23% (HR CI: 0.58, 1.02) and 28% (HR CI: 0.58, 0.93) reduction in the risk of HF, MI and stroke respectively. CVE risk was also reduced in the delayed versus non-intensified group. In conclusion, large proportion of patients remain non-intensified post basal insulin despite poor glycemic control, timely intensification in primary care is thus central in minimising CVE complications. Disclosure: M. Adan: None. S. Seidu: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Servier. Board Member; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc. Research Support; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Sanofi-Aventis. Speaker's Bureau; Self; Amgen, Lilly Diabetes, Merck Sharp & Dohme Corp. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker's Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. F. Zaccardi: Speaker's Bureau; Self; Napp Pharmaceuticals. C.L. Gillies: None. R. Lubwama: Employee; Self; Sanofi US. A.H. Boss: Employee; Self; Sanofi. Stock/Shareholder; Self; Novo Nordisk Inc., Sanofi. T.A. Dex: Consultant; Self; Sanofi US. Stock/Shareholder; Self; Bayer Healthcare Pharmaceuticals Inc., Pfizer Inc., Teva Pharmaceutical Industries Ltd. [ABSTRACT FROM AUTHOR]

Health equity is when every person can achieve their full potential for health and wellbeing. In this Viewpoint, global experts discuss the root causes and contributing factors to health inequity in endocrinology. Potential action points and research directions to help reduce health disparities are also discussed. [ABSTRACT FROM AUTHOR]

Introduction: The community deintensification rates in older people with diabetes are low and hospital admission presents an opportunity for medication review. We audited the inpatient assessment and deintensification rate in people with diabetes and frailty. We also identified factors associated with adverse inpatient outcomes. Methods: A retrospective review of electronic charts was conducted in all people with diabetes and clinical frailty score ≥ 6 who were discharged from the medical unit in 2022. Data on demographics, comorbidities and background glucose-lowering medications were collected. Results: Six-hundred-and-sixty-five people with diabetes and moderate/severe frailty were included in our analysis. For people with no HbA1c in the last six months preceding admission, only 9.0% had it assessed during inpatient. Deintensification rates were 19.1%. Factors that were associated with adverse inpatient outcomes included inpatient hypoglycaemia, non-White ethnicity, and being overtreated (HbA1c <7.0% [53 mmol/mol] with any glucose-lowering medication). Conclusion: The assessment and deintensification rate in secondary care for people with diabetes and frailty is low. Inpatient hypoglycaemia, non-White ethnicity, and overtreatment are important factors in determining inpatient outcomes highlighting the importance of deintensification and the need for an evidence-based risk stratification tool. [ABSTRACT FROM AUTHOR]

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. Those with suboptimal glycaemia (glycated haemoglobin ≥7% or ≥53 mmol/mol) within 12 months of BI initiation were divided into early (treatment intensified within 5 years), or late (≥5 years) intensification groups. We estimated the age‐stratified risks of micro‐ and macrovascular complications among these groups compared with those with optimal glycaemia (glycated haemoglobin <7%). Results: Of the 13 916 people with suboptimal glycaemia, 52.5% (n = 7304) did not receive any treatment intensification. In those aged <65 years, compared with the optimal glycaemia group late intensification was associated with a 56% higher risk of macrovascular complications (adjusted hazard ratio 1.56; 95% confidence intervals 1.08, 2.26). In elderly people (≥65 years), late intensification was associated with a higher risk of cardiovascular‐related death (1.62; 1.03, 2.54) and a lower risk of microvascular complications (0.26; 0.08, 0.83). Conclusions: Those who had late intensification were at an increased risk of cardiovascular death if they were ≥65 years and an increased risk of macrovascular complications if they were <65 years. These findings highlight the critical need for earlier intensification of treatment and adopting personalized treatment strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The clinical benefit of aspirin for the primary prevention of cardiovascular disease (CVD) in diabetes remains uncertain. To evaluate the efficacy and safety of aspirin for the primary prevention of cardiovascular outcomes and all-cause mortality events in people with diabetes, we conducted an updated meta-analysis of published randomised controlled trials (RCTs) and a pooled analysis of individual participant data (IPD) from three trials. Methods: Randomised controlled trials of aspirin compared with placebo (or no treatment) in participants with diabetes with no known CVD were identified from MEDLINE, Embase, Cochrane Library, and manual search of bibliographies to January 2019. Relative risks with 95% confidence intervals were used as the summary measures of associations. Results: We included 12 RCTs based on 34,227 participants with a median treatment duration of 5.0 years. Comparing aspirin use with no aspirin, there was a significant reduction in risk of major adverse cardiovascular events (MACE)0.89 (0.83–0.95), with a number needed to treat (NNT)of 95 (95% CI 61 to 208) to prevent one MACE over 5 years average follow-up. Evidence was lacking of heterogeneity and publication bias among contributing trials for MACE. Aspirin use had no effect on other endpoints including all-cause mortality; however, there was a significant reduction in stroke for aspirin dosage ≤ 100 mg/day 0.75 (0.59–0.95). There were no significant effects of aspirin use on major bleeding and other bleeding events, though some of the estimates were imprecise. Pooled IPD from the three trials (2306 participants) showed no significant evidence of an effect of aspirin on any of the outcomes evaluated; however, aspirin reduced the risk of MACE in non-smokers 0.70 (0.51–0.96) with a NNT of 33 (95% CI 20 to 246) to prevent one MACE. Conclusions: Aspirin has potential benefits in cardiovascular primary prevention in diabetes. The use of low dose aspirin may need to be individualised and based on each individual's baseline CVD and bleeding risk. Systematic review registration PROSPERO: CRD42019122326 [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 or COVID‐19) has been declared a pandemic by the World Health Organization and sent all countries scrambling to review emergency healthcare provisions. There is global evidence of each nation struggling to effectively manage the number of people being diagnosed with the virus. These are testing times which have not been experienced in recent generations and there are a number of insecurities regarding the management of people with COVID‐19 and cardiometabolic diseases. This review highlights the current concerns related to COVID‐19 and provides advice in terms of the therapeutic uncertainty and potential adverse harms associated with therapy when managing people, particularly those with cardiometabolic diseases, who have contracted or are at increased risk of contracting COVID‐19. [ABSTRACT FROM AUTHOR]

Aims: Hypoglycaemia is associated with increased cardiovascular risk among individuals with diabetes mellitus. It has been hypothesized that hypoglycaemia may trigger autonomic changes leading to increased cardiac arrhythmia risk. We conducted a systematic review and meta‐analysis to explore this association. Materials and methods: Ovid Medline, Embase, Scopus, Web of Science and Cochrane were searched from inception to October 10, 2017. We included studies of adults with diabetes (Type 1 or Type 2) that compared acute electrocardiogram (ECG) changes during episodes of hypoglycaemia and euglycaemia. Results: Our search resulted in 4625 citations, among which 20 studies met the predefined inclusion criteria. Finally, 12 studies were included in the descriptive analysis and 15 in the meta‐analysis. Overall hypoglycaemia was associated with a reduction in heart rate variability and an increase in arrhythmia occurrence. QTc interval length was more significantly prolonged during hypoglycaemia compared to euglycaemia (pooled mean difference [95% confidence intervals] [0.64 (0.27‐1.01], P = ·001). Subgroup analysis based on diabetes type showed that QTc prolongation occurred in individuals with Type 1 and Type 2 diabetes; however, the change between euglycaemia reached statistical significance only among individuals with Type 1 diabetes. Conclusion: Our findings suggest that hypoglycaemia results in ECG alterations that are associated with increased risk of cardiac arrhythmia, which is associated with increased cardiovascular events and mortality. More clinical studies are needed to determine the cardiac risks of hypoglycaemia in individuals with diabetes, especially in Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Foot ulcers and amputations are common conditions in people with diabetes and can considerably impact quality of life, necessitate a lengthy hospital stay and increase mortality. Preventative foot care and examination can prevent or delay ulceration, and individuals may seek information from publicly available social media resources such as YouTube. Therefore, the purpose of this study is to evaluate the educational quality and reliability of publicly available YouTube videos on diabetes foot examinations. Method: A YouTube search for "diabetic foot examination" was conducted, and the first 100 relevant English videos focused on examining the diabetic foot were included for evaluation. The Journal of the American Medical Association (JAMA) standards were used to measure video reliability. The Global Quality Score (GQS) and the Diabetes UK Annual Foot Check (DUK‐C) checklist were used to assess video educational quality. Differences in JAMA, GQS, and DUK‐C ratings were analysed after videos were sorted by topic and source. Results: The mean number of views per video was 101,311.9 ± 348,383.6, and the mean video power index was 41.6 ± 170.0. The most common upload source was from physicians (28%) and, the most popular material category was diabetes foot examination (58 videos). In terms of video reliability, 36% of videos scored 0. According to the GQS standards, only 5% of the videos are of excellent quality, while 34% are of poor quality, with 24 videos scoring between 0 and 1 on the DUK‐C scale. Conclusion: While foot care examination videos have a substantial audience, the majority are considered low in quality and reliability. Videos on comprehensive diabetic foot examination should be accessed on reputable sources that guarantee standardisations of video quality and take into account the simplification of information transmission in order to reach lay audiences. [ABSTRACT FROM AUTHOR]

To evaluate how sociodemographic factors influence educational modality preferences in people with cardiometabolic disease. This was a cross-sectional study performed in people with diabetes and cardiovascular disease, who completed a questionnaire to denote their previous experience and ranked preferences for different educational modalities. The questionnaire was completed by 3751 people, of whom 59% were men, median (interquartile range) age was 68 (59−76) years, and 78% were White European. In total, 73% had diabetes, 35% had heart disease, and 10% had history of stroke; the majority (83.4%) had one of these conditions. Overall preference was for one-to-one education (77% ranked first choice), and telephone education ranked the lowest. People tended to prefer modalities they had previously experienced. We highlight the importance of considering factors that could influence selection of educational modalities including age, ethnicity, gender and educational level. We anticipate this approach will aid in the design, delivery and tailoring of educational programmes that are accessible to the diverse cohort of people living with chronic diseases, including diabetes and cardiovascular disease. Given the influence of multiple demographic factors and previous experiences on expressed preferences, providers should support individuals to make informed decisions about educational interventions to maximise engagement. • Education modality preferences differ with age, ethnicity, and educational level. • One-to-one education was the most preferred and telephone the least preferred. • Targeting individual's education modality preferences may help support uptake. • A range of modalities should be available to suit the needs of diverse populations. [ABSTRACT FROM AUTHOR]

Aim: The aim of this systematic review is to explore the attitudes of older adults (≥65 years old) and their carers towards de‐prescribing. Methods: We identified relevant studies from three databases; MEDLINE, CINAHL and Web of Science. Two reviewers (MS, SS) independently extracted data from each selected study using a standardised self‐developed data extraction form. Main findings of the studies were summarised descriptively. Results: A total of 35 studies were included in the review. Of them, 19 were questionnaire studies, 11 semi‐structured interviews, 4 focus groups and 1 study used the nominal group technique approach. Most older adults and their carers were willing to have medication de‐prescribed if told to do so by a healthcare professional (HCP). Other factors that increased willingness to de‐prescribing included; trust in the HCP, side effects and inconvenience from medications as well as the prospect of follow‐up and monitoring during de‐prescribing. In contrast, perceived effectiveness, unawareness of lack of benefit, negative expectations of ageing and fear were factors preventing de‐prescribing. Conclusion: De‐prescribing is an important concept in older people given the harm associated with polypharmacy in this age group. Overall, older adults and their carers are willing to have medication de‐prescribed if facilitated by their HCP. However, there remain a few barriers to de‐prescribing which may need to be addressed in certain patients, through discussions between older adults/their carers and a HCP, to allow de‐prescribing to be more effective. [ABSTRACT FROM AUTHOR]

Disease burden in people with diabetes is mainly driven by long-term complications such as cardiovascular disease, heart failure and chronic kidney disease. This is a consequence of the interconnection between the cardiovascular, renal and metabolic systems, through a continuous chain of events referred to as 'the cardiorenal metabolic continuum'. Increasing evidence suggests that sodium–glucose cotransporter 2 inhibitors (SGLT2is) have beneficial effects across all stages of the cardiorenal metabolic continuum, reducing morbidity and mortality in a wide range of individuals, from those with diabetes and multiple risk factors to those with established heart failure and chronic kidney disease, regardless of the presence of diabetes. Despite this robust evidence base, the complexity of label indications and misconceptions concerning potential side effects have resulted in a lack of clear understanding in primary care regarding the implementation of SGLT2is in clinical practice. With this in mind, we provide an overview of the clinical and economic benefits of SGLT2is across the cardiorenal metabolic continuum together with practical considerations in order to help address some of these concerns and clearly define the role of SGLT2is in primary care as a holistic outcomes-driven treatment with the potential to reduce disease burden across the cardiorenal metabolic spectrum. [ABSTRACT FROM AUTHOR]

The article provides an update on the risks associated with SARS-CoV-2 and COVID-19 among individuals with diabetes. Topics discussed include the updated risk assessment for type 1 vs. type 2 diabetes concerning SARS-CoV-2, the differential impact of insulin use on COVID-19 outcomes in diabetics, and the influence of DPP-4 inhibitors on the risks.

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. Face to face primary and specialist care consultations, with either a nurse or general practitioner, were assessed over time in subjects with T2DM, CVD, or cardiometabolic multimorbidity. Changes in the average length of consultation in each group were investigated. Results: 696,255 (mean 4.9 years [95% CI, 2.02–7.66]) person years of follow up time, there were 10,221,798 primary and specialist care consultations. The crude rate of primary and specialist care consultations in patients with cardiometabolic multimorbidity (N = 11,881) was 18.5 (95% CI, 18.47–18.55) per person years, 13.5 (13.50, 13.52) in patients with T2DM only (N = 83,094) and 13.2 (13.18, 13.21) in those with CVD (N = 57,974). Patients with cardiometabolic multimorbidity had 28% (IRR 1.28; 95% CI: 1.27, 1.31) more consultations than those with only T2DM. Patients with cardiometabolic multimorbidity had primary care consultation rates decrease by 50.1% compared to a 45.0% decrease in consultations for those with T2DM from 2000 to 2018. Specialist care consultation rates in both groups increased from 2003 to 2018 by 33.3% and 54.4% in patients with cardiometabolic multimorbidity and T2DM, respectively. For patients with T2DM the average consultation duration increased by 36.0%, in patients with CVD it increased by 74.3%, and in those with cardiometabolic multimorbidity it increased by 37.3%. Conclusions: Annual primary care consultation rates for individuals with T2DM, CVD, or cardiometabolic multimorbidity have fallen since 2000, while specialist care consultations and average consultation length have both increased. Individuals with cardiometabolic multimorbidity have significantly more consultations than individuals with T2DM or CVD alone. Service redesign of health care delivery needs to be considered for people with cardiometabolic multimorbidity to reduce the burden and health care costs. [ABSTRACT FROM AUTHOR]

BACKGROUND: This review was commissioned by the World Health Organization and presents a summary of the latest research evidence on the impact of coronavirus disease 2019 (COVID-19) on people with diabetes (PWD). PURPOSE: To review the evidence regarding the extent to which PWD are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or of suffering its complications, including associated mortality. DATA SOURCES: We searched the Cochrane COVID-19 Study Register, Embase, MEDLINE, and LitCOVID on 3 December 2020. STUDY SELECTION: Systematic reviews synthesizing data on PWD exposed to SARS-CoV-2 infection, reporting data on confirmed SARS-CoV-2 infection, admission to hospital and/or to intensive care unit (ICU) with COVID-19, and death with COVID-19 were used. DATA EXTRACTION: One reviewer appraised and extracted data; data were checked by a second. DATA SYNTHESIS: Data from 112 systematic reviews were narratively synthesized and displayed using effect direction plots. Reviews provided consistent evidence that diabetes is a risk factor for severe disease and death from COVID-19. Fewer data were available on ICU admission, but where available, these data also signaled increased risk. Within PWD, higher blood glucose levels both prior to and during COVID-19 illness were associated with worse COVID-19 outcomes. Type 1 diabetes was associated with worse outcomes than type 2 diabetes. There were no appropriate data for discerning whether diabetes was a risk factor for acquiring SARS-CoV-2 infection. LIMITATIONS: Due to the nature of the review questions, the majority of data contributing to included reviews come from retrospective observational studies. Reviews varied in the extent to which they assessed risk of bias. CONCLUSIONS: There are no data on whether diabetes predisposes to infection with SARS-CoV-2. Data consistently show that diabetes increases risk of severe COVID-19. As both diabetes and worse COVID-19 outcomes are associated with socioeconomic disadvantage, their intersection warrants particular attention. [ABSTRACT FROM AUTHOR]

Aim: To investigate factors associated with delays in receiving glucose‐lowering therapy in patients newly diagnosed with type 2 diabetes mellitus (T2DM), and explore the preferential order and time of intensifications. Materials and Methods: Retrospective cohort study including 120 409 adults with T2DM initiating first‐ to fourth‐line glucose‐lowering therapy in primary care between 2000 and 2018, using the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics, Office of National Statistics death registration, and 2007 Index of Multiple Deprivation data. Associations were investigated using time‐to‐event analysis. Results: The longest delays to prescription of first‐line therapy were observed in older patients, of black or other ethnicities, and with multimorbidity. People from the most deprived areas received earlier first‐line treatment than those from the least deprived areas. The majority were treated with metformin (82.4%) as the first‐line prescription, sulphonylurea (50.4%) as second‐line, dipeptidyl peptidase‐4 inhibitor (27.7%) as third‐line, and insulin (28.0%) as fourth‐line. In the past 5 years, there was an increase in prescriptions of dipeptidyl peptidase‐4‐inhibitor and sodium‐glucose transport protein‐2 inhibitor. The median time was 0.5 years for first‐line prescription, 4.1 for second‐line, 4.6 for third‐line and 4.7 for fourth‐line. After T2DM diagnosis, 25% of patients developed cardiovascular disease and non‐cardiovascular disease complications within a median time of 12‐14 years, and received intensification 5‐6 years later. Conclusions: Within the complex challenges of managing blood glucose levels and risk of additional comorbidities, future health care research and guidelines should focus on overcoming therapeutic inertia particularly at an earlier stage for older patients, from ethnic minorities and with multimorbidities. [ABSTRACT FROM AUTHOR]

Background: Pre-existing comorbidities have been linked to SARS-CoV-2 infection but evidence is sparse on the importance and pattern of multimorbidity (2 or more conditions) and severity of infection indicated by hospitalisation or mortality. We aimed to use a multimorbidity index developed specifically for COVID-19 to investigate the association between multimorbidity and risk of severe SARS-CoV-2 infection.Methods: We used data from the UK Biobank linked to laboratory confirmed test results for SARS-CoV-2 infection and mortality data from Public Health England between March 16 and July 26, 2020. By reviewing the current literature on COVID-19 we derived a multimorbidity index including: (1) angina; (2) asthma; (3) atrial fibrillation; (4) cancer; (5) chronic kidney disease; (6) chronic obstructive pulmonary disease; (7) diabetes mellitus; (8) heart failure; (9) hypertension; (10) myocardial infarction; (11) peripheral vascular disease; (12) stroke. Adjusted logistic regression models were used to assess the association between multimorbidity and risk of severe SARS-CoV-2 infection (hospitalisation/death). Potential effect modifiers of the association were assessed: age, sex, ethnicity, deprivation, smoking status, body mass index, air pollution, 25-hydroxyvitamin D, cardiorespiratory fitness, high sensitivity C-reactive protein.Results: Among 360,283 participants, the median age was 68 [range 48-85] years, most were White (94.5%), and 1706 had severe SARS-CoV-2 infection. The prevalence of multimorbidity was more than double in those with severe SARS-CoV-2 infection (25%) compared to those without (11%), and clusters of several multimorbidities were more common in those with severe SARS-CoV-2 infection. The most common clusters with severe SARS-CoV-2 infection were stroke with hypertension (79% of those with stroke had hypertension); diabetes and hypertension (72%); and chronic kidney disease and hypertension (68%). Multimorbidity was independently associated with a greater risk of severe SARS-CoV-2 infection (adjusted odds ratio 1.91 [95% confidence interval 1.70, 2.15] compared to no multimorbidity). The risk remained consistent across potential effect modifiers, except for greater risk among older age. The highest risk of severe infection was strongly evidenced in those with CKD and diabetes (4.93 [95% CI 3.36, 7.22]).Conclusion: The multimorbidity index may help identify individuals at higher risk for severe COVID-19 outcomes and provide guidance for tailoring effective treatment. [ABSTRACT FROM AUTHOR]

Aims: The primary aim was to evaluate the effectiveness of a model integrating diabetes services across primary, secondary and community care (Transformation model). The secondary aim was to understand whether changes resulted from the model. Methods: The model was implemented In Leicester, Leicestershire and Rutland (UK) across three clinical commissioning groups, the acute trust and accompanying stakeholders. One clinical commissioning group (Leicester City) implemented the entire model and was the primary evaluation population. A quasi‐experimental interrupted time series design was employed. The primary outcome was number of Type 2 diabetes‐related bed‐days per 1000 patients. Results: In the primary population, the mean number of Type 2 diabetes‐related bed‐days per 1000 patients was increasing before model implementation by 0.33/month (95% confidence interval: −0.07, 0.72), whereas it was decreasing after implementation by a mean value of −0.14/month (−0.33, 0.06); a statistically significant difference (p = 0.04). Secondary analyses showed: nationally, there was no significant change between the pre‐ and post‐periods so it is unlikely that large secular change drove the improvement; the other two Leicestershire clinical commissioning groups saw improvement or stability; underlying processes worked as hypothesised overall; diabetes biomedical markers deteriorated in the primary care population suggesting a change in case‐mix due to moving some patients out of secondary care. Conclusions: Given that the initial aim was to shift services from secondary to primary care without causing harm, an improvement is better than expected. This observational evaluation cannot show conclusively that improvements were due to the Transformation model, but secondary analyses support this. [ABSTRACT FROM AUTHOR]

Objective: To estimate the relative and absolute risk of severe hypoglycemia and mortality associated with glucose control, sulfonylureas, and insulin treatment in elderly people with type 2 diabetes.Research Design and Methods: We identified elderly subjects (≥70 years old) with type 2 diabetes between 2000 and 2017 in the U.K. Clinical Practice Research Datalink primary care database with linkage to hospitalization and death data. Subjects with three consecutive HbA1c values <7% (53 mmol/mol) while on insulin and/or sulfonylureas within 60 days prior to the third HbA1c value (exposed) were matched with subjects not exposed. Hazard ratios (HRs) and absolute risks were estimated for hospitalizations for severe hypoglycemia and cardiovascular and noncardiovascular-related mortality.Results: Among 22,857 included subjects (6,288 [27.5%] exposed, of whom 5,659 [90.0%] were on a sulfonylurea), 10,878 (47.6%) deaths and 1,392 (6.1%) severe hypoglycemic episodes occurred during the follow-up. In comparison with nonexposed subjects, the adjusted HR in exposed subjects was 2.52 (95% CI 2.23, 2.84) for severe hypoglycemia, 0.98 (0.91, 1.06) for cardiovascular mortality, and 1.05 (0.99, 1.11) for noncardiovascular mortality. In a 70-, 75-, 80-, and 85-year-old subject, the 10-year risk of severe hypoglycemia was 7.7%, 8.1%, 8.6%, and 8.4% higher than in nonexposed subjects, while differences for noncardiovascular mortality ranged from 1.2% (95% CI -0.1, 2.5) in a 70-year-old to 1.6% (-0.2, 3.4) in an 85-year-old subject. Sulfonylurea and insulin use were more relevant predictors of severe hypoglycemia and death than were glucose levels.Conclusions: Elderly subjects with type 2 diabetes and low HbA1c on sulfonylurea or insulin treatment experienced a substantially higher risk of hospitalization for severe hypoglycemia but had no clear evidence of increased risks of mortality. [ABSTRACT FROM AUTHOR]

Aims: To compare the effectiveness and safety of gliclazide modified release (MR) to sitagliptin as type 2 diabetes mellitus (T2D) treatments in a real‐world patient population. Materials and Methods: This retrospective cohort study used records from the UK Clinical Practice Research Datalink. The cohort consisted of adult patients with T2D newly treated with either gliclazide MR or sitagliptin as second‐line treatment added to metformin and with a glycated haemoglobin (HbA1c) level of ≥7.0% (53 mmol/mol). Patients were 1:1 matched using high‐dimensional propensity score matching and followed to determine the time taken to reach an HbA1c <7.0%. Secondary outcomes included time to HbA1c ≤6.5% (48 mmol/mol), time to ≥1% (11 mmol/mol) HbA1c reduction from baseline, treatment persistence and durability, and hypoglycaemic events. Results: Among the 1986 patients included, those on gliclazide MR more likely achieved an HbA1c <7.0% [hazard ratio (HR): 1.35; 95% confidence interval (CI): 1.15‐1.57], HbA1c ≤6.5% (HR: 1.51; 95% CI: 1.19‐1.92) or had an HbA1c reduction ≥1% from baseline (HR: 1.11; 95% CI: 1.00‐1.24) compared with patients on sitagliptin. Durability (log‐rank P =.135) and persistence (P =.119) were similar between the two groups. Hypoglycaemic events were uncommon (23 total severe and non‐severe events; incidence rate, 3.7 per 1000 patient years), with 4.7 and 2.6 events per 1000 patient years with gliclazide MR and sitagliptin treatment, respectively. Conclusions: In this real‐world study, second‐line gliclazide MR was more effective than sitagliptin in reducing HbA1c, with similar durability and persistence and low rates of hypoglycaemic events, in individuals with T2D on metformin treatment and HbA1c above the target of 7.0%. [ABSTRACT FROM AUTHOR]

Aim: To evaluate if, one year after notification of possible overtreatment, diabetes care providers de-intensified glucose-lowering medications and to gain insight into the opinions and beliefs of both care providers and patients regarding de-intensification. Methods: Mixed methods using routine care data from five health-care centres in the Netherlands. Patient characteristics and medication prescription of patients, previously identified as possibly over-treated, were extracted from patients' medical records. Opinions of care providers were obtained through interviews. Patients received questionnaires about their diabetes treatment and were asked to participate in focus groups. Results: A total of 64 elderly patients with type 2 diabetes were previously identified as possibly over-treated and included; 57.8% male, median age 75 years (IQR=72–82), median diabetes duration 12 years (IQR=8–18). De-intensification was implemented in more than half (n=36) of them. Care providers preferred person-centred care above just setting general HbA1c target values, considering patient characteristics (such as comorbidity) and patient's preference. Patients valued glucose levels as most important in determining their treatment. Both patients and care providers felt that de-intensification should occur gradually. Conclusion: Treatment had been de-intensified in more than half of the patients (56.3%). Insight in reasons for not de-intensifying elderly patients is important since treatment for them can be "person-centred care". De-intensification is an iterative and time-intensive process. [ABSTRACT FROM AUTHOR]

Objective: Low serum albumin concentration is associated with poor health outcomes, but its relationship with the risk of fractures has not been reliably quantified. We aimed to assess the prospective association of serum albumin with the risk of fractures in a general population.Subjects and Methods: Baseline serum albumin concentrations were measured in 2,245 men aged 42-61 years in the Kuopio Is-chemic Heart Disease study. Hazard ratios (HRs) (95% confidence intervals) were calculated for incident fractures.Results: A total of 121 fractures (hip, humeral, or wrist) were recorded during a median follow-up of 25.6 years. The risk of fractures increased linearly below a serum albumin concentration of ∼48 g/L. The age-adjusted HR (95% CI) for fractures per 1 standard deviation lower serum albumin was 1.24 (1.05-1.48). On further adjustment for several conventional and emerging risk factors, the HR was attenuated to 1.21 (1.01-1.45). Comparing the bottom versus top quartile of serum albumin levels, the corresponding adjusted HRs were 2.48 (1.37-4.48) and 2.26 (1.23-4.14). The association of serum albumin with fracture risk did not differ substantially according to age, body mass index, blood pressure, physical activity, alcohol consumption, socioeconomic status, inflammation, prevalent diseases, and smoking. Serum albumin at a threshold of 41.5 g/L demonstrated an area under the curve of 0.5850.Conclusion: In middle-aged Caucasian men, low serum albumin is associated with an increased risk of future fractures. The potential relevance of serum albumin concentrations in fracture prevention and prediction deserves further evaluation. [ABSTRACT FROM AUTHOR]

Aims: Smoking is a strong risk factor for albuminuria in people with type 2 diabetes mellitus (T2DM). However, it is unclear whether this sequela of smoking is brought about by its action on cardiometabolic parameters or the relationship is independent. The aim of this systematic review is to explore this relationship. Methods: Electronic databases on cross-sectional and prospective studies in Medline and Embase were searched from January 1946 to May 2018. Adult smokers with T2DM were included, and other types of diabetes were excluded. Results: A random effects meta-analysis of 20,056 participants from 13 studies found that the odds ratio (OR) of smokers developing albuminuria compared to non-smokers was 2.13 (95% CI 1.32, 3.45). Apart from smoking, the odds ratio of other risk factors associated with albuminuria were: age 1.24 (95% CI 0.84, 1.64), male sex 1.39 (95% CI 1.16, 1.67), duration of diabetes 1.78 (95% CI 1.32, 2.23), HbA1c 0.63 (95% CI 0.45, 0.81), SBP 6.03 (95% CI 4.10, 7.97), DBP 1.85 (95% CI 1.08, 2.62), total cholesterol 0.06 (95% CI − 0.05, 0.17) and HDL cholesterol − 0.01 (95% CI − 0.04, 0.02), triglyceride 0.22 (95% CI 0.12, 0.33) and BMI 0.40 (95% CI 0.00–0.80). When the smoking status was adjusted in a mixed effect meta-regression model, the duration of diabetes was the only statistically significant factor that influenced the prevalence of albuminuria. In smokers, each year's increase in the duration of T2DM was associated with an increased risk of albuminuria of 0.19 units (95% CI 0.07, 0.31) on the log odds scale or increased the odds approximately by 23%, compared to non-smokers. Prediction from the meta-regression model also suggested that the odds ratios of albuminuria in smokers after a diabetes duration of 9 years and 16 years were 1.53 (95% CI 1.10, 2.13) and 5.94 (95% CI 2.53, 13.95), respectively. Conclusions: Continuing to smoke and the duration of diabetes are two strong predictors of albuminuria in smokers with T2DM. With a global surge in younger smokers developing T2DM, smoking cessation interventions at an early stage of disease trajectory should be promoted. [ABSTRACT FROM AUTHOR]

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). 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. A total of 12,556 patients were analysed. Compared to individuals aged < 65 years, those aged ≥ 65 years had lower risk of treatment intensification (HR: 0.69; 95% CI: 0.64–0.73). Other factors included being female (0.93, 0.89–0.99), longer T2DM duration (0.99, 0.98–0.99), living in the most deprived areas (0.90, 0.83–0.98), being a current smoker (0.91, 0.84–0.98), having one (0.91, 0.85–0.97) or more than one comorbidity (0.88, 0.82–0.94), and patients who were on metformin (0.71, 0.63–0.80), or 2nd generation sulphonylureas (0.85; 0.79–0.92) or DPP4 inhibitors (0.87, 0.82–0.93) compared to those who were not. Therapeutic inertia still remains a major barrier, with multiple factors associated with delay in intensification. Interventions to overcome therapeutic inertia need to be implemented at both patient and health care professional level. [ABSTRACT FROM AUTHOR]

Objective: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a new method to objectively and robustly detect nonadherence. We applied this technique to study nonadherence to cardiovascular medications in people with type 2 diabetes (T2DM).Research Design and Methods: Routine urine samples, received at the time of the annual diabetes review from 228 people with T2DM in primary care, were assessed for adherence by LC-MS/MS.Results: A total of 28.1% patients (N = 64) were nonadherent to antidiabetic, antihypertensive, and/or lipid-lowering medications. Nonadherence to statins was the highest at 23.7%, and nonadherence to oral hypoglycemic agents was 9.3%. HbA1c, albumin-to-creatinine ratio, and lipid profiles were significantly higher in the patients who were nonadherent compared with those who were adherent to treatment.Conclusions: This unique study shows that routine urine samples can be used for adherence testing screening by LC-MS/MS and has demonstrated high nonadherence rates especially to statins in people with T2DM. Future intervention studies using LC-MS/MS as a diagnostic/therapeutic tool may help to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Aims: To conduct a systematic review and meta‐analysis of published observational evidence to assess the difference in the prevalence and progression of diabetic nephropathy, and the development of end‐stage renal disease (ESRD) in people from three different ethnic groups with type 2 diabetes (T2DM). Materials and methods: Relevant studies were identified in a literature search of MEDLINE, EMBASE and reference lists of relevant studies published up to May 2018. We decided a priori that there were no differences in the prevalence and progression of diabetic nephropathy, and the development of ESRD in the three ethnicities with T2DM. Pooled relative risks of microalbuminuria by ethnicity were estimated by fitting three random effects meta‐analyses models. A narrative synthesis of the nephropathy progression in the studies was carried out. The review was registered in PROSPERO (CRD42018107350). Results: Thirty‐two studies with data on 153 827 unique participants were eligible for inclusion in the review. The pooled prevalence ratio of microalbuminuria in South Asian compared with white European participants was 1.14 (95% confidence interval [CI] 0.99, 1.32; P = 0.065), while for African Caribbean vs South Asian participants the pooled prevalence ratio was 1.08 (95% CI 0.93, 1.24; P = 0.327). Results for renal decline were inconsistent, with preponderance towards a high rate of disease progression in South Asian compared with white participants. The estimated pooled incidence rate ratio (IRR) for ESRD was significantly higher in African Caribbean vs white European participants: 2.75 (95% CI 2.01, 3.48; P < 0.001). Conclusion: The results of this review did not show a significant link between ethnicity (South Asian, white European and African Caribbean) and the prevalence of microalbuminuria; however, the IRR for ESRD in African Caribbean compared with white European participants was significantly higher. Further research is needed to explore the potential non‐albuminuric pathways of progression to ESRD. [ABSTRACT FROM AUTHOR]

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker of acute kidney injury, might play a role in the development of atherosclerotic cardiovascular disease (CVD). We aimed to assess the association of circulating NGAL with CVD risk. Materials and methods Plasma NGAL concentrations were measured at baseline in 5275 participants in the PREVEND prospective study. Hazard ratios (95% confidence intervals [CI]) for CVD were estimated. Results After a median follow-up of 8.3 years, 338 participants developed first CVD events. Plasma NGAL was weakly to moderately correlated with several CVD risk markers. There was a non-linear relationship between NGAL and CVD risk. In analyses adjusted for established risk factors, the hazard ratio (95% CI) for CVD in a comparison of the top quartile versus bottom quartiles 1–2 of NGAL values was 1.35 (1.05–1.75; P = 0.022), which was abrogated after additional adjustment for other potential confounders (mainly attributed to high sensitivity C-reactive protein) 1.20 (0.92–1.57; P = 0.176). The association was considerably attenuated following further adjustment for renal function 1.05 (0.79–1.40; P = 0.745). The association between NGAL and CVD risk did not vary importantly in relevant clinical subgroups. Conclusion Evidence suggests a non-linear association between NGAL and CVD risk, which is dependent on inflammation and renal function. Highlights • Increased NGAL is associated with an increased CVD risk in Caucasians. • The association is non-linear and is independent of cardiovascular risk factors. • The association is partly dependent on inflammation and renal function. [ABSTRACT FROM AUTHOR]

Background and aims We aimed to assess the association of circulating calprotectin, an inflammation-associated protein, with cardiovascular disease (CVD) risk and determine whether it improves risk prediction. Methods Plasma calprotectin measurements were made at baseline in 5290 participants in the PREVEND prospective study. Hazard ratios (95% confidence intervals [CI]) for CVD were calculated. Results After a median follow-up of 8.3 years, 339 first CVD events were recorded. Calprotectin concentration was correlated with several conventional risk factors as well as with high-sensitivity C-reactive protein (hsCRP) (r = 0.42). Calprotectin was log-linearly associated with CVD risk. The risk for CVD adjusted for conventional cardiovascular risk factors was 1.26 (95% CI, 1.13–1.41) per 1 standard deviation higher baseline log e calprotectin, and was 1.24 (95% CI, 1.11–1.39) following further adjustment for triglycerides, body mass index, and other potential confounders. The association remained present after further adjustment for hsCRP 1.15 (95% CI, 1.02–1.30). Comparing extreme quartiles of plasma calprotectin levels, the corresponding adjusted HRs for CVD were 1.96 (1.37–2.82), 1.89 (1.31–2.72), and 1.56 (1.07–2.29). The association of calprotectin with CVD risk did not vary importantly in several relevant clinical subgroups. Adding calprotectin to the Framingham CVD Risk Score was associated with a C-index change (0.0016; p =0.42) difference in −2 log likelihood ( p =0.038), IDI (0.0080; p  < 0.001), and NRI (4.03%; p =0.024). Conclusions There is a log-linear association of calprotectin concentration with risk of CVD, which may be partly dependent on hsCRP. Adding calprotectin to conventional risk factors improves CVD risk assessment using measures of reclassification and −2 log likelihood. [ABSTRACT FROM AUTHOR]

Background: Smoking is associated with increased macrovascular and microvascular complications in people with diabetes. In addition to other concomitant vascular perturbations, it also seems to influence the cardiometabolic parameters, which may partly explain the accelerated rate of vascular complications in smokers with diabetes. While smoking cessation is advocated as a universal component of the management of diabetes, there is some anecdotal evidence that HbA1c could increase following smoking cessation. The aim of this review is to explore the relationship between smoking and its cessation on cardiometabolic parameters in diabetes. Methods: Searches were conducted on Medline, EMBASE and CINAHL up to March 2016. After screening 6866 studies (Additional file 1), 14 observational studies with a total of 98,978 participants' with either type 1 or type 2 diabetes were selected for review. Narrative synthesis and meta-analyses were carried out to explore the relationship between smoking and its cessation. Results: Meta-analysis showed that the pooled mean difference of HbA1c between non-smokers and smokers was -0.61% (95% CI -0.88 to -0.33, p < 0.0001). The difference in LDL cholesterol between non-smokers and smokers was -0.11 mmol/l (95% CI -0.21 to -0.01, p = 0.04). The difference in HDL cholesterol between non-smokers and smokers was 0.12 mmol/l (95% CI 0.08-0.15, p < 0.001). However, there was no statistically significant difference in blood pressure between the two groups. The difference in HbA1c between quitters and continued smokers was not statistically significant -0.10% (95% CI -0.42 to 0.21, p = 0.53). However, a narrative synthesis revealed that over a period of 10 years, the HbA1c was comparable between non-smokers and quitters. Conclusion: Non-smokers have a statistically significant lower HbA1c and more favourable lipid profile compared to smokers. Smoking cessation does not lead to an increase in HbA1c in long-term and may reduce vascular complications in diabetes by its favourable impact on lipid profile. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend metformin as first-line therapy in people with type 2 diabetes (T2D). Many patients will eventually need dual therapy; sulfonylureas (SUs) and dipeptidyl-peptidase 4 inhibitors (DPP-4i) remain the most commonly prescribed second-line therapies. Available evidence, mostly from RCTs, generally indicates greater HbA1c reductions with SUs. No real-world comparative effectiveness studies have compared gliclazide MR, a later generation SU, and sitagliptin, the most commonly used DPP-4i. Aim: To investigate the effectiveness of gliclazide MR vs. sitagliptin as second-line therapies in people with T2D uncontrolled on metformin monotherapy. Methods: New users of gliclazide MR or sitagliptin were identified (1:1 high-dimensional propensity score matching) in the UK Clinical Practice Research Datalink (CPRD) database between 1/1/2010 and 21/10/2019, from a cohort of adults with T2D. A Cox model was used to estimate time to HbA1c <7.0% (primary outcome); secondary outcomes included time to HbA1c ≤6.5%. Results: A total of 2346 patients (59.3% men; mean age 63 years, HbA1c 8.5%, diabetes duration 4.3 years) were included. Patients were 28% more likely to reach HbA1c <7% (HR [95% CI]: 1.28 [1.10-1.49]) and 50% more likely to reach HbA1c ≤6.5% (1.50 [1.19-1.93]) with gliclazide MR vs. sitagliptin. The difference in favour of gliclazide MR was maintained across patients' characteristics (ethnicity, cardiorenal disease, age, diabetes duration, baseline HbA1c). Durability (time until switch or an add-on of a new drug or a stop) and persistence (duration of index drug) were similar. There was no significant difference in severe and nonsevere hypoglycaemic events. Conclusion: These results demonstrate greater real-world effectiveness of gliclazide MR vs. sitagliptin as second-line therapy after metformin, with a similar persistence, durability and rate of hypoglycaemia. Disclosure: F. Zaccardi: Speaker's Bureau; Self; Napp Pharmaceuticals. V. Cortese: Employee; Self; Servier. E. Jacquot: Employee; Self; Servier. F. Tyrer: None. S. Seidu: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Servier. Board Member; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc. Research Support; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Sanofi-Aventis. Speaker's Bureau; Self; Amgen, Lilly Diabetes, Merck Sharp & Dohme Corp. M.J. Davies: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi, Sanofi US. Speaker's Bureau; Self; Boehringer Ingelheim International GmbH, Napp Pharmaceuticals, Novo Nordisk A/S, Sanofi. Other Relationship; Self; Ingeus UK. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker's Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. [ABSTRACT FROM AUTHOR]