Opportunistic screening for asymptomatic left ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice. OBJECTIVE: To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM). METHOD: A prospective screening study at the DM complication screening centre was performed. RESULTS: Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%. CONCLUSION: NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Discovery of insulin 100 years on.

The discovery of insulin 100 years ago ranks among the greatest medical achievements ever. This sparked a revolution of scientific discovery and therapeutic intervention to treat people suffering with diabetes. A light was shone for other areas of medicine to illuminate what was possible with detailed scientific endeavour. There followed a range of firsts leading to the current time in which we now know more about this peptide hormone than almost any other protein in existence. This has allowed therapeutic advancement from a positon of knowledge leading to stunning innovation. This innovation is likely to lead to more physiological insulin replacement reducing the disease burden to individuals and society as whole.

Uric acid and diabetes mellitus: an update.

The relationship between diabetes mellitus (DM) and high serum uric acid is complex and controversial. Many epidemiological studies have reported a positive association, whereas others have reported an inverse association or none. In the pathogenesis of DM it is the intracellular urate that is more important than the extracellular and dissociation between the two is possible. Evidence suggests that high serum uric acid induces insulin resistance and beta cell failure in animal models. Reduction of intracellular uric acid can be achieved by dietary measures such as reducing fructose and salt intake, and uric acid-lowering drugs. We suggest that in the Western diet, these elements play a crucial role in pathogenesis of DM. To determine the precise and exact interrelationship between intracellular and extracellular uric acid, well-designed studies are required. Besides this, clinical trials are needed to determine whether intracellular and extracellular urate reduction will provide benefit in prevention and treatment of DM and complications associated with it.

Zinc supplementation ameliorates type 2 diabetes markers through the enhancement of total antioxidant capacity in overweight patients.

BACKGROUND: Evidence show that the recommended dose of zinc may not be sufficient for controlling pathological conditions such as type 2 diabetes mellitus (T2DM). AIM: This study aimed to evaluate the effects of zinc supplementation on the oxidative status in overweight T2DM. In addition, the routine glycaemic parameters were determined and compared in zinc-treated and placebo groups. METHODS: In this randomised, double-blind, placebo-controlled trial, 70 patients with T2DM were selected. They were divided into two groups for supplementation of 50 mg zinc gluconate or placebo (zinc group, n=35; placebo group, n=35) per day for 8 weeks. Blood samples were collected from all the individuals in the zinc group and controls for analysis. RESULTS: The results showed that zinc supplementation to patients with T2DM for 8 weeks significantly inhibited serum levels of lipid peroxidation (25%), nitrotyrosine (30%) and total oxidant status levels (25%, p<0.05). Nevertheless, the total antioxidant capacity was significantly elevated (16%) following zinc intake by patients with T2DM. CONCLUSIONS: These data, together with our previous report, may suggest that the control in the glycaemic condition in overweight patients with T2DM is correlated with the antioxidative/oxidative balance following intake of 50 mg zinc supplementation for 8 weeks. Under these circumstances, the clinical and glycaemic indices, including fasting blood glucose, insulin, haemoglobin A1c and homeostasis model of assessment-insulin resistance, were controlled. TRIAL REGISTRATION NUMBER: IRCT2015083102.

rs10865710 polymorphism in PPARG promoter is associated with the severity of type 2 diabetes mellitus and coronary artery disease in a Chinese population.

BACKGROUND: Relationship between polymorphisms in peroxisome proliferator-activated receptor gamma (PPARG) and progression of type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) remains to be clarified. METHODS: 635 subjects were divided into T2DM, CAD, T2DM complicated with CAD (T2DM/CAD) and control groups according to diagnostic criteria. The rs10865710 and rs3856806 polymorphisms were genotyped, and the severity of T2DM and CAD was evaluated for all subjects. RESULTS: In patients with T2DM, G allele carriers of rs10865710 polymorphism had significantly higher levels of glucose, triglycerides, apolipoprotein B (ApoB) and lipoprotein (a) (Lp(a)) than non-carriers, T allele carriers of rs3856806 polymorphism had significantly higher levels of glucose, low-density lipoprotein cholesterol (LDL-C), ApoB and Lp(a) than non-carriers. In patients with CAD, G allele carriers of rs10865710 polymorphism had significantly higher levels of total cholesterol (TC), ApoB and Lp(a) than non-carriers, T allele carriers of rs3856806 polymorphism had significantly higher levels of body mass index, blood pressure, TC, LDL-C and ApoB than non-carriers. Patients with one or two G alleles of rs10865710 polymorphism had significantly higher levels of Gensini scores and more diseased coronary branches than those patients without CAD. The rs3856806 polymorphism was not associated with CAD severity, but it was found to be significantly associated with T2DM/CAD, T allele frequency was significantly higher in T2DM/CAD group than that in T2DM/CAD-free group. CONCLUSIONS: The rs10865710 and rs3856806 polymorphisms in PPARG are significantly associated with glucose levels in patients with T2DM. The rs10865710 polymorphism is significantly associated with the severity of CAD, which is possibly mediated by hyperlipidaemia and hyperglycaemia.

Is HbA1c an ideal biomarker of well-controlled diabetes?

HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes, although not a perfect one. Common comorbidities encountered in patients with diabetes mellitus, such as renal insufficiency, high output states (iron deficiency anaemia, haemolytic anaemia, haemoglobinopathies and pregnancy) and intake of specific drugs could compromise the sensitivity and specificity of the biomarker. COVID-19 pandemic poses a pressing challenge for the diabetic population, since maintaining optimal blood glucose control is key to reduce morbidity and mortality rates. Alternative methods for diabetes management, such as fructosamine, glycosylated albumin and device-based continuous glucose monitoring, are discussed.

The role of community pharmacists and their position in the delivery of diabetes care: an update for medical professionals.

Pharmacists are the third largest group of healthcare professionals worldwide, but are underused in the delivery of diabetes care. The aim of this narrative was to describe how integration of community pharmacy services into existing healthcare models may improve diabetes care. Relevant literature exploring pharmacy-led interventions for diabetes were identified from a search of Medline, Embase and Cinahl online databases. This review highlights that community pharmacists are accessible, experts in medicine management, trusted by the public and able to achieve financial savings. They are poorly integrated into existing healthcare models, and commissioning arrangements can be poorly perceived by the public and those working in primary care. Community pharmacy interventions in type 2 diabetes have similar, if not greater effects compared to those delivered by other healthcare professionals. It was concluded that community pharmacy interventions in diabetes are feasible, acceptable and deliver improved health outcomes. Future work should build public recognition of pharmacists and improve communication between them and other healthcare professionals.

Endocrine changes in SARS-CoV-2 patients and lessons from SARS-CoV.

Coronavirus infection outbreaks have occurred frequently in the last two decades and have led to significant mortality. Despite the focus on reducing mortality by preventing the spread of the virus, patients have died due to several other complications of the illness. The understanding of pathological mechanisms and their implications is continuously evolving. A number of symptoms occur in these patients due to the involvement of various endocrine glands. These clinical presentations went largely unnoticed during the first outbreak of severe acute respiratory syndrome (SARS) in 2002-2003. A few of these derangements continued during the convalescence phase and sometimes occurred after recovery. Similar pathological and biochemical changes are being reported with the novel coronavirus disease outbreak in 2020. In this review, we focus on these endocrine changes that have been reported in both SARS coronavirus and SARS coronavirus-2. As we battle the pandemic, it becomes imperative to address these underlying endocrine disturbances that are contributing towards or predicting mortality of these patients.

An overview of GLP-1 agonists and recent cardiovascular outcomes trials.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are emerging as an important therapy to consider for patients with type 2 diabetes (T2D) given this class of treatment's ability to reduce glycated haemoglobin and their associated weight loss and low risk for hypoglycaemia. Additionally, seven cardiovascular outcomes trials (CVOTs) have been performed in the past 4 years using lixisenatide, liraglutide, semaglutide, exenatide, albiglutide, dulaglutide and oral semaglutide. All have found non-inferiority for cardiovascular outcomes, with many finding superiority of these drugs. These findings have transformed our guidelines on pharmacological treatment of T2D. This review article will discuss GLP-1 RA therapy, review the seven CVOTs reported to date and discuss the implications on current guidelines and therapies going forward.

Trends in the prevalence of cardiometabolic disease and cardiovascular events by body mass index category in adults from 1999 to 2016.

OBJECTIVES: An increasing percentage of the US population is obese. Cardiometabolic risk in the population increases with body mass index (BMI), but whether this correlation changes over time is unknown. We analysed the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2016 to determine if the prevalence of cardiometabolic disease and cardiovascular events within each BMI category is changing over time as the BMI of the population is increasing. STUDY DESIGN: For each of the nine survey cycles covering this period, we divided the population by BMI category (normal, overweight, class 1 obesity, class ≥2 obesity) and subsequently by the presence of cardiovascular events or cardiometabolic disease. NHANES participants are a group of 5000 individuals/cycle selected to be representative of the US population. We used the weighted data sets to perform trend analyses for each risk/BMI group adjusted for relevant confounders. RESULTS: The distribution of the highest risk category (cardiovascular event) has not changed over time within any BMI category. The distribution of the lowest risk category (cardiometabolically healthy) increased significantly over time in all BMI categories. This was noted in the 18- to 45-year subgroup but not in the group aged >45 years. CONCLUSIONS: The increase in the prevalence of overweight and obese individuals might be associated with a 'healthy obesity' phenotype in those <45 years; however, individuals >45 years showed a proportional increase in associated cardiometabolic risk.

Trends in antidiabetes medication use among hospitalised patients with type 2 diabetes: a retrospective single-centre cohort study.

OBJECTIVES: Novel antidiabetes medications with proven cardiovascular or renal benefit, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), have been introduced to the market. This study explored the 4-year trends of antidiabetes medication use among medical hospitalisations with type 2 diabetes (T2D). DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital in Switzerland. PARTICIPANTS: 4695 adult hospitalisations with T2D and prevalent or incident use of one of the following antidiabetes medications (metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), sulfonylureas, GLP-1 RA, SGLT-2i, short-acting insulin or long-acting insulin), identified using electronic health record data. Quarterly trends in use of antidiabetes medications were plotted overall and stratified by cardiovascular disease (CVD) and chronic kidney disease (CKD). RESULTS: We observed a stable trend in the proportion of hospitalisations with T2D who received any antidiabetes medication (from 77.6% during 2019 to 78% in 2022; p for trend=0.97). In prevalent users, the largest increase in use was found for SGLT-2i (from 7.4% in 2019 to 21.8% in 2022; p for trend <0.01), the strongest decrease was observed for sulfonylureas (from 11.4% in 2019 to 7.2% in 2022; p for trend <0.01). Among incident users, SGLT-2i were the most frequently newly prescribed antidiabetes medication with an increase from 26% in 2019 to 56.1% in 2022 (p for trend <0.01). Between hospital admission and discharge, SGLT-2i also accounted for the largest increase in prescriptions (+5.1%; p<0.01). CONCLUSIONS: These real-world data from 2019 to 2022 demonstrate a significant shift in antidiabetes medications within the in-hospital setting, with decreased use of sulfonylureas and increased prescriptions of SGLT-2i, especially in hospitalisations with CVD or CKD. This trend aligns with international guidelines and indicates swift adaptation by healthcare providers, signalling a move towards more effective diabetes management.

Cohort profile: the 'Biomarkers of heterogeneity in type 1 diabetes' study-a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands.

PURPOSE: The 'Biomarkers of heterogeneity in type 1 diabetes' study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D). PARTICIPANTS: Data and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected. FINDINGS TO DATE: Stimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia. FUTURE PLANS: Research groups are invited to consider the use of these data and the sample collection. Future work will include additional hormones, beta-cell-directed autoimmunity, specific immune markers, microRNAs, metabolomics and gene expression data, combined with glucometrics, anthropometric and clinical data, and additional markers of residual beta-cell function. TRIAL REGISTRATION NUMBER: NCT04977635.

Association of carotid intima-media thickness and dyslipidaemia in patients with type 2 diabetes: a protocol for systematic review and meta-analysis.

INTRODUCTION: Patients with diabetes mellitus (DM) often present with comorbidities such as hypertension, dyslipidaemia, insulin resistance, obesity and hyperglycaemia, which increases their risk of cardiovascular diseases (CVDs)-related mortality. Carotid intima-media thickness (CIMT), a biomarker for subclinical atherosclerosis, has been associated with overall CVD, especially in type 2 DM (T2DM). Hence, this protocol for systematic review and meta-analysis aims to review existing literature on the association of CIMT and dyslipidaemia in patients with T2DM. METHODS AND ANALYSIS: The proposed systematic review and meta-analysis will be conducted according to an updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guideline. A comprehensive search of peer-reviewed studies on Google Scholar, PubMed, Science Direct and Web of Sciences databases will be conducted up to 30 June 2023. A meta-analysis of data extracted from selected studies will be performed to explore the association between dyslipidaemia and CIMT in patients with diabetes. The effect estimates will be reported as standardised mean differences/Cohen's d and 95% CIs. A random effect model will be used in case of high heterogeneity whereas fixed-effect model will be used in the absence of heterogeneity. All statistical analysis will be performed using SPSS V.29.0 software. In cases of high heterogeneity, subgroup analysis will be performed based on study design, countries of publication and body mass index to identify potential sources of heterogeneity. Publication bias will be assessed graphically via funnel plots and statistically using Egger's regression test. Sensitivity analysis will also be performed to evaluate the stability of the overall effect size and the grading of recommendations assessment, development and evaluation will be used to grade the quality of analysed evidence. ETHICS AND DISSEMINATION: As the proposed study will use secondary published data, approval will not be sought from the ethics committee. PROSPERO REGISTRATION NUMBER: CRD42023451731.

Clinical evaluation of the reference intervals for diabetes in Chinese geriatric population: a cross-sectional cohort study protocol.

INTRODUCTION: Diabetes mellitus (DM) is an important health issue that affects the ageing population. China has the largest geriatric population and the largest number of diabetes cases in the world. This poses a significant challenge for healthcare providers and policymakers. Haemoglobin A1C (HbA1c), which is one of the diagnostic criteria for diabetes, is affected by many factors such as pregnancy, age, race and anaemia. Glycated albumin (GA) is not influenced by factors that affect HbA1c concentrations, although it has been used in the diagnosis of diabetes in a few people. The aim of this study protocol is to determine reference intervals (RIs) of HbA1c and GA for the diagnosis of older adults with diabetes in China and to assess the optimal cut-off values for these parameters from a health economic perspective. METHODS AND ANALYSIS: This cross-sectional survey study will recruit 1278 community-dwelling older adults aged 60-89 in Chengdu City. The data collection process will involve a questionnaire survey, a comprehensive physical examination and the collection of blood samples for laboratory testing. Data analyses will be conducted on the pooled sample and stratified by gender, age or other demographic features if necessary. Rates will be compared using the χ2 test or Fisher test and receiver operating characteristic (ROC) curves will be used to identify the most effective threshold values for HbA1c and GA for diagnosing diabetes among older adults in China. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics review board of the Bioethics Subcommittee of West China Hospital, Sichuan University (Approval No. 1705 in 2022). The study's results will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300070831.

Intersectoral health interventions to improve the well-being of people living with type 2 diabetes: a scoping review protocol.

INTRODUCTION: Intersectoral collaboration is a collaborative approach between the health sectors and other sectors to address the interdependent nature of the social determinants of health associated with chronic diseases such as diabetes. This scoping review aims to identify intersectoral health interventions implemented in primary care and community settings to improve the well-being and health of people living with type 2 diabetes. METHODS AND ANALYSIS: This protocol is developed by the Arksey and O'Malley (2005) framework for scoping reviews and the Levac et al methodological enhancement. MEDLINE, Embase, CINAHL, grey literature and the reference list of key studies will be searched to identify any study, published between 2000 and 2023, related to the concepts of intersectorality, diabetes and primary/community care. Two reviewers will independently screen all titles/abstracts, full-text studies and grey literature for inclusion and extract data. Eligible interventions will be classified by sector of action proposed by the Social Determinants of Health Map and the conceptual framework for people-centred and integrated health services and further sorted according to the actors involved. This work started in September 2023 and will take approximately 10 months to be completed. ETHICS AND DISSEMINATION: This review does not require ethical approval. The results will be disseminated through a peer-reviewed publication and presentations to stakeholders.

What is the coverage of retina screening services for people with diabetes? Protocol for a systematic review and meta-analysis.

INTRODUCTION: Diabetic retinopathy is a leading cause of vision impairment globally. Vision loss from diabetic retinopathy can generally be prevented by early detection and timely treatment. The WHO included a measure of service access for diabetic retinopathy as a core indicator in the Eye Care Indicator Menu launched in 2022: retina screening coverage for people with diabetes. The aim of this review is to provide a comprehensive global and regional summary of the available information on retina screening coverage for people with diabetes. METHODS AND ANALYSIS: A search will be conducted in five databases without language restrictions for studies from any country reporting retina screening coverage for adults with any type of diabetes at the national or subnational level using data collected since 1 January 2000 until the search date. We will also seek reports and coverage statistics from government websites of all WHO member states. Two investigators will independently screen studies, extract relevant data and assess risk of bias of included studies. The results of the review will be reported using the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. We will summarise the range of coverage definitions reported across included studies and present the median retina screening coverage in WHO regions and by World Bank country income level. Depending on the availability of data, we will conduct meta-analysis to assess disparities in retina screening coverage for people with diabetes by factors in the PROGRESS framework (Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status and Social capital). ETHICS AND DISSEMINATION: This review will only include published data thus no ethical approval will be sought. The findings of this review will be published in a peer-reviewed journal and presented at relevant conferences. PROTOCOL REGISTRATION NUMBER: OSF registration 17/10/2023: https://osf.io/k5p69.