The Republic of Srpska (RS), as a part of the Western Balkans (WB) region, has a higher diabetes prevalence than the EU. This study aims to assess the cost-effectiveness of early treatment of high-risk patients with pre-diabetes and undiagnosed diabetes in our setting. We designed a Markov chain Monte Carlo (MCMC) model which reflects the current International Diabetes Federation (IDF) three-step plan for the prevention of T2DM in those at increased risk. The model captures the evolution of the disease in FINDRISC high-risk patients from normal glucose tolerance (NGT) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) and then to T2DM and its complications. We developed two MCMC models, in order to follow the progression of the disease in high-risk cases, ie, when early treatment is undertaken or when it is not undertaken. The health costs and quality adjusted life years (QALY) were discounted at an annual rate of 3%. The key model parameters were varied in one-way and probabilistic sensitivity analysis. Early treatment resulted in increased life expectancy, postponement of the onset of diabetes and increased QALY for all patients. The discounted incremental cost-effectiveness-ratios (ICER) in NGT, IFG, IGT, and T2DM patients were -289.9, 9724.03, -1478.59 and 4084.67 €. In high-risk IGT patients, ICER was the most favorable, being both a cost saving and QALY gaining, with the consistent results confirmed by the sensitivity analysis. The results recommend the acceptance of a new health policy of identifying IGT patients with the use of FINDRISC questionnaire and plasma glucose measurements; providing them with a lifestyle change program; and implementing intensive diabetes treatment, as their disease progresses. Our results are especially significant for the Western Balkan countries, since this was the first cost-effectiveness study of T2DM prevention in this region.

The effect of the duration of medication with metformin and sulfonylurea (SUs) on microvascular complications based on the duration of type 2 diabetes (DM2) is unclear. The aim of this study was to investigate the association of medication time with metformin and SUs and microvascular complications in newly diagnosed DM2 patients.

In this prospective multi-cohort study, data from 3,904 newly diagnosed DM from three cohorts of the Tehran Lipid and Glucose Study (TLGS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Atherosclerosis Risk in Communities (ARIC) with a mean age of 59.6 ± 08 years were pooled. Metformin medication time alone, SUs alone, and a combination of both since drug initiation were defined as exposure. The incidence of microvascular complications (diabetic nephropathy or retinopathy) was defined as outcomes. The cumulative exposure to metformin, SUs, aspirin, statin, and anti-hypertensive medication was also determined using the same approach.

Metformin alone, SUs alone, and the combination of both reduced the hazard of microvascular complications by 8%(HRAdj: 0.92, 95% CI: 0.89, 0.96, P: 0.001), 6%(HRAdj: 0.94, 95% CI: 0.92, 0.97, P: 0.004), and 9%(HRAdj: 0.91, 95% CI: 0.89, 0.94, P: 0.001) for each year of use, respectively (p < 0.05). The protective effect of metformin and SUs, individually or in combination, on microvascular complications started approximately five years after the initial treatment and continued until approximately 15 years after the initial treatment and then reached a plato.

long-term use of metformin and SUs individually and in combination was associated with a decrease in the risk of microvascular outcomes in newly diagnosed DM for up to about one decade. These findings highlight the importance of choosing an appropriate treatment regimen for new patients with type 2 diabetes. Appropriate oral therapy can minimize microvascular complications and improve overall well-being.

The online version contains supplementary material available at 10.1007/s40200-025-01577-w.

Peripheral arterial disease (PAD) is a complication of type 2 diabetes mellitus (T2DM). No systematic review and meta-analysis has been conducted regarding the risk factors of PAD in T2DM populations.

To analyze the pooled effect estimates of risk factors of PAD in T2DM populations.

A systematic literature search was conducted in PubMed/MEDLINE, ProQuest, and EMBASE databases. The Newcastle-Ottawa Scale was used to assess the risk of bias. Meta-analysis was performed using RevMan version 5.4.

Ten studies were included in this review (73,834 samples in total). All the studies had a low risk of bias. Significant association with PAD in T2DM was found in the group of age ≥ 70 years old (OR 3.44; 95 % CI 2.11, 5.62), diabetes duration ≥ 5 years (OR 1.81; 95 % CI 1.24, 2.64), coronary artery disease (CAD) history (OR 1.55; 95 % CI 1.30, 1.83), hypertension (OR 1.43; 95 % CI 1.10, 1.86), and increased LDL (OR 2.51; 95 % CI 1.38, 4.56).

Age ≥ 70 years old, diabetes duration ≥ 5 years, CAD history, hypertension, and increased LDL are significant risk factors for PAD in the T2DM population.

Type 2 diabetes is a global public health challenge characterized by high prevalence and poor self-management outcomes. The PRECEDE-PROCEED model is a well-known conceptual widely used to promote health in chronic diseases. This meta-analysis evaluated the efficacy of interventions based on PRECEDE-PROCEED model in reducing Glycated Hemoglobin A1c (HbA1c) and enhancing self-management in patients with type 2 diabetes.

Nine online databases-PubMed, Cochrane Library, Embase, PsycINFO, Scopus, CINAHL, Web of Science, CNKI, and WANFANG-were searched from inception to June 2024. Randomized controlled trials (RCTs) and quasi-experimental studies (QESs) were identified using keywords related to the PRECEDE-PROCEED model, type 2 diabetes, and self-management. Review Manager 5.4 was used for meta-analysis and the 95% confidence intervals (CIs) was calculated for standardized mean differences (SMDs) or weighted mean differences (WMDs).

Fourteen studies (11 RCTs and 3 QESs) involving 2,478 patients met the eligibility criteria. Interventions significantly reduced HbA1c, with progressive improvements over time: WMD = -0.41 (95% CI: -0.58 to -0.24) at 1 month, -0.50 (95% CI: -0.67 to -0.33) at 3 months, and -0.63 (95% CI: -0.93 to -0.33) at 6 months. Significant improvements were also observed in total self-management scores (SMD = 2.53; 95% CI: 1.14to 3.91) and in key PRECEDE-PROCEED model variables, including knowledge, attitudes, self-efficacy, reinforcing, and enabling factors, though high heterogeneity was noted.

The PRECEDE-PROCEED model is an effective framework for reducing HbA1c and enhancing self-management among patients with type 2 diabetes. Future research should focus on standardizing intervention protocols and developing unified outcome measures to improve reproducibility and cross-study comparability.

The PROSPERO registration ID is CRD42024600814.

A large body of evidence supports the long-term benefits of intensive glycemic control for patients with type 2 diabetes mellitus (T2DM). However, the relationship between intensive glycemic control and diabetic retinopathy (DR) progression in T2DM patients in the short-term remains under debate. Therefore, we investigated the effect of intensive glycemic control on DR changes in the short-term.

A total of 254 patients with T2DM, all exhibition hemoglobin A1c (HbA1c) levels above 7% were included in the study. We collected HbA1c values at baseline and after 12-months. HbA1c control classified into two categories: intensive control, targeting an HbA1c of less than 7%, and less intensive control, targeting an HbA1c of 7% or higher at 12-month follow-up. The severity of DR were graded based on seven-field 45° conventional fundus photographs examinations according to the United Kingdom National Diabetic Eye Screening Program guidelines.

After a one-year follow-up, 129 participants achieved a target HbA1c of less than 7% and 125 achieved 7% or more. We found no significant difference in DR changes (incidence, progression, or regression) between two groups after adjustments for age and gender. Further adjustments for confounding factors such as body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), diabetes duration, insulin use and baseline HbA1c, revealed no association between intensive glycemic control and the DR changes.

This prospective cohort study demonstrates that intensive glycemic control did not associated with DR changes in T2DM patients in the short term. Further research is required to ascertain the long-term effects of intensive glycemic control on DR.

The trail has been registered at The UK's Clinical Study Registry ( https://www.isrctn.com ) on 2020/04/13 (ISRCTN15853192).

Diabetes is a well-established risk factor for stroke. Understanding the pathophysiology of this connection is crucial to implementing appropriate prevention strategies. Lately, there has been a paradigm shift in the care of individuals with diabetes toward the use of glucose-lowering medications with potential cardiovascular, cerebrovascular or cardiorenal benefits. The aim of this article is to provide a critical analysis of the role of diabetes in cerebrovascular disease and current evidence and recommendations for the use of glucose-lowering medication with particular focus on the sodium glucose cotransporter-2 inhibitor (SGLT2i) class.

Intensive glycemic control in individuals with diabetes reduces the risk of microvascular complications, but there is less clear evidence for decreasing risk of macrovascular events (e.g., stroke). A multifaceted management of diabetes addressing healthy lifestyle practices, glycemic control, and optimization of other cardiovascular risk factors is highly recommended. SGLT2i are the latest class of antihyperglycemic agents available for diabetes management. Canagliflozin and empagliflozin are associated with reduction in major adverse cardiovascular events (MACE). Dapagliflozin did not reduce the rate of MACE but is associated with reduction in heart-failure related death and hospitalization and has the potential to decrease dementia risk. Ertugliflozin decreases rates of hospitalization related to heart failure however it was non-inferior to placebo in reducing MACE. There is increasing evidence that the use of SGLT2i may reduce the risk of stroke, particularly hemorrhagic stroke, in individuals with type 2 diabetes and a high risk of cardiovascular events, and that SGLT2i may also be beneficial for brain health by decreasing risk of cognitive decline and dementia. Antihyperglycemic therapy should be tailored to patients' circumstances. SGLT2i treatment should be considered in patients with type 2 diabetes and established or high-risk cardiovascular disease, heart failure, or chronic kidney disease, to reduce the overall cerebro-cardiovascular and renal risks.

This study aimed to examine the associations between visit-to-visit variability in fasting plasma glucose (FPG) and HbA1c with echocardiographic variables in patients with type 2 diabetes using epidemiologic and Mendelian randomization (MR) methods.

From January 2001 to December 2020, 2,326 (1,233 men and 1,093 women) subjects with type 2 diabetes who underwent echocardiography assessment were enrolled in the diabetes care management program of a medical center in Taiwan. The echocardiographic variables included those for cardiac structural, cardiac systolic, and diastolic function. Variability in FPG and HbA1c within one-year prior echocardiographic measurements was calculated using coefficient of variation (CV). A two-stage multivariable regression analysis was used to assess the causal relationship among FPG-CV, HbA1c-CV, and echocardiographic variables using 22 SNPs for FPG and 14 SNPs for HbA1c as instrumental variables.

A total of 2,326 participants were included, with a mean age of 64.5 years and 53.0% were men. Epidemiologic and MR analyses show the significant associations between left atrium diameter (LAD), left ventricular systolic diameter (LVSd), left ventricular mass (LVM), left ventricular ejection fraction (LVEF), E, and E/e' ratio with FPG variability. Significant associations between HbA1c variability and echocardiographic variables including LAD, E/e', and deceleration time identified in the epidemiologic approach became non-significant in the MR analysis when controlling for covariates.

Our epidemiologic and MR studies demonstrated that visit-to-visit variability of FPG in patients with type 2 diabetes was independently associated with the left cardiac structure as well as systolic and diastolic function.

The growing morbidity, mortality, and health care costs related to heart failure (HF) underscore the urgent need to prioritize its primary prevention. Whereas a risk-based approach for HF prevention remains in its infancy, several key opportunities exist to actualize this paradigm in clinical practice. First, the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America HF guidelines provided recommendations, for the first time, on the clinical utility of multivariable risk equations to estimate risk of incident HF. Second, the American Heart Association recently developed the PREVENT (Predicting Risk of Cardiovascular Disease Events) equations, which not only enable prediction of incident HF separately, but also include HF in the prediction of total cardiovascular disease. Third, the predominant phenotype of HF risk has emerged as the cardiovascular-kidney-metabolic syndrome. Fourth, the emergence of novel therapies that prevent incident HF (eg, sodium-glucose cotransporter-2 inhibitors) and target multiple cardiovascular-kidney-metabolic axes demonstrate growing potential for risk-based interventions. Whereas the concept of risk-based prevention has been established for decades, it has only been operationalized for atherosclerotic cardiovascular disease prevention to date. Translating these opportunities into a conceptual framework of risk-based primary prevention of HF requires implementation of PREVENT-HF (Predicting Risk of Cardiovascular Disease Events-Heart Failure) equations, targeted use of cardiac biomarkers (eg, natriuretic peptides) and echocardiography for risk reclassification and earlier detection of pre-HF, and definition of therapy-specific risk thresholds that incorporate net benefit and cost-effectiveness. This scientific statement reviews the current evidence for accurate risk prediction, defines strategies for equitable prevention, and proposes potential strategies for the successful implementation of risk-based primary prevention of HF.

To determine the effects of artesunate (ART) on bone remodeling in vivo under orthodontic stress in diabetic rats and explore the underlying mechanisms in vitro.

A rat model of type 2 diabetes mellitus with orthodontic tooth movement was established. The rats received ART and/or metformin (Met) orally. The effects of ART and Met on periodontium changes were evaluated using tartrate-resistant acid phosphatase and immunohistochemical staining. Molecular docking analyses were employed to investigate the mechanisms of ART action. In vitro, the effects of ART on osteogenic and osteoclastic activity were explored by examining TRAF6 and NF-κB expression under hyperglycemic and static pressure conditions via immunofluorescence and Western blotting.

ART enhanced bone metabolism despite hyperglycemia, though mechanical stress still induced bone resorption. Treatment with ART alone or in combination with Met promoted osteogenesis. TRAF6, NF-κB and the OPG/RANKL/RANK signaling pathways have been identified as key mediators of these effects. The expression of the osteogenesis-associated factor OPG increased after ART and Met treatment, while that of TRAF6 and the osteoclast-associated factors RANKL and NF-κB decreased.

Increased bone resorption and decreased bone formation are characteristics of type 2 diabetes, impacting orthodontic tooth movement. ART administration alone promotes bone remodeling under static pressure and hyperglycemic conditions. These effects are mediated by lowering blood sugar levels, inhibiting osteoclast function, and improving osteogenesis through mechanisms closely associated with the OPG/TRAF6/NF-κB signaling pathway.

Diabetes is a widespread disease associated with long-term complications. Treatment of diabetes alleviates these complications but cause an increased risk of recurrent hypoglycemia (RH). Hypoglycemia exposure increases the risk of cardiovascular events by an unknown mechanism. Since the effect of mild/moderate hypoglycemia on thrombosis is unknown, we studied the effect of RH exposure on platelet function and thrombosis in insulin-treated diabetic (ITD) rats.

ITD rats were randomized to either control or hypoglycemia groups. First, we determined the minimum duration and frequency of RH exposure that increases the risk of thrombosis and the time window after a single hypoglycemic episode (SH)/RH exposure with increased risk of thrombosis in male ITD rats. Next, we confirmed whether RH exposure increases the risk of thrombosis in female ITD rats. Subsequently, we evaluated the impact of RH exposure on platelet susceptibility to aggregation and platelet gene expression.

One hour hypoglycemia increased the clot weight and the effect of SH and RH on thrombosis lasted for at least 1 and 7 days post-exposure, respectively. A minimum frequency of twice-a-week hypoglycemia exposure for 6 weeks increased the risk of thrombosis in male ITD rats. Increased susceptibility of platelet activation was observed in RH-exposed male ITD rats. Lastly, we identified RH-induced alterations in the platelet transcriptome in male ITD rats. We also confirmed that RH exposure increases the risk of thrombosis in female rats.

Understanding the mechanism of RH-induced platelet activation and thrombosis may help limit thrombotic complications in diabetes.

This study sought to determine whether the association between attaining specific glycated hemoglobin (HbA1c) targets (<7.0% (<53 mmol/mol) and ≥8.0% (≥64 mmol/mol) compared with 7.0%-7.9%) over time and risk of incident coronary artery disease (CAD) was dependent on haptoglobin (Hp) phenotype in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study.

Prospectively collected HbA1c data from the ADVANCE biomarker case-cohort study, updated at 6 months and every 12 months thereafter over a median of 5.0 (IQR 4.5-5.3) years, were analyzed in relation to incident CAD in the Hp2-2 (n=1323) and non-Hp2-2 (n=2069) phenotypes separately using weighted multivariable-adjusted Cox regression models. Additional a priori stratifications by sex, race, previous cardiovascular disease (CVD), and type 2 diabetes duration were performed.

Mean HbA1c was similar in each phenotype group throughout the study. Compared with HbA1c of 7.0%-7.9%, HbA1c <7.0% was not associated with CAD risk for any phenotype group or subgroup. HbA1c ≥8.0% compared with 7.0%-7.9% over time was associated with higher CAD risk for the Hp2-2 phenotype only (HR 1.53, 95% CI 1.01 to 2.32; no significant association in the non-Hp2-2 type: 1.26, 0.89 to 1.77, p-interaction=0.71); this was pronounced when those with previous CVD at baseline were excluded (Hp2-2: 2.80, 1.41 to 5.53, p-interaction=0.03). Compared with HbA1c of <8.0%, having HbA1c ≥8.0% was associated with a 59% higher CAD risk among participants with the Hp2-2 phenotype (1.59, 1.12 to 2.26) and a 39% higher CAD risk among participants without the Hp2-2 phenotype (1.39, 1.03 to 1.88, p-interaction=0.97).

The present ADVANCE analysis suggests that not having HbA1c ≥8.0%, rather than achieving HbA1c <7.0%, was found to be particularly important for CAD prevention among people with type 2 diabetes and the common Hp2-2 phenotype. While the subgroup analyses were likely underpowered, their inclusion is hypothesis generating and can be used in future meta-analyses to improve power and generalizability.

To estimate the number of screenings received, life-years (LYs) saved, and number of screenings per LY saved per woman who participated in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) (Program) compared with those who did not participate (no Program).

We developed a time-to-event simulation model to compare the outcomes of women participating in the Program vs. no Program, categorized by race/ethnicity. Model input parameters included data from the Program's minimum data elements, United States Cancer Statistics, National Health Interview Survey, and published literature. The Program's impact was calculated as the difference in LYs between the Program and no Program using data from 2010 to 2019.

Among 1 million women of all races/ethnicities who participated in the NBCCEDP in the last 10 years, 457,152 (standard deviation [SD]: 848) received more screenings than those who did not participate. These participants saved an average of 0.027 LYs per woman screened. In addition, we estimated that about 17 screenings would be required to save an additional 1 LY per woman screened in the Program compared with no Program. Per woman screened by race/ethnicity, non-Hispanic Black women had the highest estimated 0.075 LYs saved, followed by Hispanic women with 0.025 LYs, non-Hispanic White with 0.014 LYs, and non-Hispanic American Indian/Alaska Native and Asian/Pacific Islander had the least health outcome with 0.011 LYs.

The reported findings underscore the importance of providing preventive health services to populations that might not otherwise have access to these services.

Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness among individuals with diabetes mellitus. Current clinical diagnostic criteria mainly base on visible vascular structure changes, which are insufficient to identify diabetic patients without clinical DR (NDR) but with dysfunctional retinopathy. This review focuses on retinal endothelial cells (RECs), the first cells to sense and respond to elevated blood glucose. As blood glucose rises, RECs undergo compensatory and transitional phases, and the correspondingly altered molecules are likely to become biomarkers and targets for early prediction and treatment of NDR with dysfunctional retinopathy. This article elaborated the possible pathophysiological processes focusing on RECs and summarized recently published and reliable biomarkers for early screening and emerging intervention strategies for NDR patients with dysfunctional retinopathy. Additionally, references for clinical medication selection and lifestyle recommendations for this population are provided. This review aims to deepen the understanding of REC biology and NDR pathophysiology, emphasizes the importance of early detection and intervention, and points out future directions to improve the diagnosis and treatment of NDR with dysfunctional retinopathy and to reduce the occurrence of DR.

Aims: In subjects with type 2 diabetes (DM), poor glycemic control, and advanced chronic kidney disease (CKD), the kidney benefit of the reduction of glycated hemoglobin (HbA1c) is not well established. Methods: In a retrospective cohort, we included patients with DM, CKD grade 3b-5, and HbA1c > 9% to evaluate the risk of developing major adverse kidney events (MAKE) defined as the start of kidney replacement therapy (KRT), ≥ 25% or ≥ 40% decline in the glomerular filtration rate (eGFR) from baseline, and death; patients were divided according to the HbA1c levels at the end of the follow-up into the following groups: > 75 mmol/mol (≥ 9.0%), 74-64 mmol/mol (8.9%-8.0%), 64-53 mmol/mol (7.9%-7.0%), and < 52 mmol/mol (< 7.0%). We described their characteristics and analyzed their risks, adjusting for confounding variables. Results: From 2015 to 2023, 111 patients were included. In 46 patients (41.4%), the HbA1c at the end of follow-up (60 months) was still > 75 mmol/mol (≥ 9%), and each patient had a mean of 4.9 HbA1c measurements. The mean age was 59 years, and 46% were male; the baseline eGFR was 25 mL/min/1.73 m2. MAKE occurred in 67% of cases. In a multivariate analysis, the risk of MAKE was not associated with the HbA1c groups, nor was it associated with any of the MAKE components individually, nor in certain subgroups. When evaluating the magnitude of percentage changes in HbA1 with the initiation of KRT, we did not find any association. Conclusions: With advanced CKD and poor glycemic control, changes in HbA1c during long follow-up are not associated with MAKE or its individual components.

It is unclear whether poor glycemic control contributes to residual kidney function (RKF) decline and consequent volume overload in diabetic patients on peritoneal dialysis (PD).

This retrospective analysis included 80 diabetic patients who started PD at a single center. The first 2 years of patient data were collected to investigate the impact of glycemic control on RKF and volume overload in the early stages of PD. We used the time-averaged glycated hemoglobin (HbA1c) levels to estimate glycemic control. RKF loss was measured as the slope of RKF decline and time to anuria. To assess the association between glycemic control and volume overload, we examined technique failure (TF) associated with volume overload (TFVO), defined as TF due to excessive fluid accumulation. Multivariable linear regression and Cox regression analysis were performed to assess how glycemic control affects RKF and TFVO.

Over the first 2 years, the mean rate of RKF decline was -3.25 ± 3.94 mL/min/ 1.73 m2 per year. Multivariable linear regression showed that higher time-averaged HbA1c was associated with a rapid RKF decline (β = -0.95; 95% confidence interval [CI], -1.66 to -0.24; p = 0.01). In the adjusted Cox regression analysis, higher time-averaged HbA1c increased the risk of progression to anuria (adjusted hazard ratio [HR], 1.97; 95% CI, 1.29-3.00; p = 0.002) and TFVO (adjusted HR, 2.88; 95% CI, 1.41-5.89; p = 0.004).

Poor glycemic control is associated with rapid RKF decline and leads to volume overload in diabetic patients on PD.

Cardiovascular disease is the most common complication and cause of death in people with diabetes. Hypoglycaemia is independently associated with the development of cardiovascular complications, including death. The aim of this study was to assess changes in cardiac function and workload during acute hypoglycaemia in people with and without diabetes and to explore the role of diabetes type, magnitude of the adrenaline response, and other phenotypic traits.

We enrolled people with type 1 diabetes (n = 24), people with insulin-treated type 2 diabetes (n = 15) and controls without diabetes (n = 24). All participants underwent a hyperinsulinaemic-normoglycaemic-(5.3 ± 0.3 mmol/L)-hypoglycaemic (2.8 ± 0.1 mmol/L)-glucose clamp. Cardiac function was assessed by echocardiography, with left ventricular ejection fraction (LVEF) as the primary endpoint.

During hypoglycaemia, LVEF increased significantly in all groups compared to baseline (6.2 ± 5.2%, p < 0.05), but the increase was significantly lower in type 1 diabetes compared to controls without diabetes (5.8 ± 3.4% vs. 9.4 ± 5.0%, p = 0.03, 95% CI difference: -5.0, -0.3). In people with type 1 diabetes, ΔLVEF was inversely associated with diabetes duration (β: -0.16, 95% CI: -0.24, -0.53, p = 0.001) and recent exposure to hypoglycaemia (β: -0.30, 95% CI: -0.53, -0.07, p = 0.015). Hypoglycaemia also increased global longitudinal strain (GLS) in controls without diabetes (p < 0.05), but this did not occur in the two diabetes subgroups (p > 0.10).

Hypoglycaemia increased LVEF in all groups, but the increase diminished with longer disease duration and prior exposure to hypoglycaemia in type 1 diabetes, suggesting adaptation to recurrent hypoglycaemia. The increment in GLS observed in controls was blunted in people with diabetes. More research is needed to determine the clinical relevance of these findings.

Cerebrovascular diseases have caused substantial social and economic burdens, and new treatment methods are urgently needed. Evaluating the feasibility of the use of antidiabetic drugs for treating cerebrovascular diseases is meaningful in this field. We designed a comprehensive study process that includes two-sample Mendelian randomization (MR), which uses genetic proxies for antidiabetic drug targets, summary-based MR (SMR) for mRNAs, and colocalization for drug target genes to assess their causal relationships with 10 cerebrovascular disease phenotypes. Seven of the eight main types of clinical antidiabetic drugs were identified, yielding eleven potential drug targets. Our study observed that sulfonylureas (KCNJ11) and metformin (GPD1) reduce the risk of stroke and that TZDs (PPARG) reduce the risk of hippocampal perivascular spaces. In addition, sulfonylureas can reduce the risk of certain cerebral small vessel disease. These results show that antidiabetic drugs have hypoglycemic properties and affect cerebrovascular health. Our study supports repurposing antidiabetic drugs as disease-modifying therapies to improve cerebrovascular health. Future research should focus on studying the role of drugs in different phenotypes of cerebrovascular diseases and explore the potential molecular mechanisms to analyze further the potential effects of antidiabetic drugs on cerebrovascular diseases.

Internet-based self-management of diabetes has been demonstrated to be effective. The frequency of social media is believed to be associated with diabetes management, yet the quality and applicability of online information are still subject to debate. The dynamic nature of online information complicates its study, making it crucial to further assess the online behaviors and psychological aspects of the population engaged in online blood glucose management.

The objective of this study was to explore the relationship between the frequency of social media usage and the suggestibility of internet health information.

This study is a secondary analysis based on data obtained from a prior cross-sectional survey conducted in multiple online diabetes communities in China, which received a total of 5,504 responses, ultimately including 1,062 individuals with diabetes or prediabetes for analysis. Frequency of social media usage was measured using a 6-point Likert scale across five items, evaluating the frequency of use on platforms such as WeChat, Weibo, QQ, TikTok, and others. Suggestibility by internet health Information was assessed using a 5-point Likert scale across nine items reflecting individuals' trust in, discussion of, and engagement with internet health information and communities. Data analysis was conducted using R language and EmpowerStats software, encompassing Chi-square tests, U tests, multifactor linear regression analysis, smooth curve fitting, and subgroup and interaction effect analysis.

After adjusting for other factors, there was a positive correlation between the frequency of social media and the suggestibility of internet health information cues (β = 0.27, 95% CI: 0.24 to 0.30, P < .001). A nonlinear relationship was identified, with a turning point at 3.8. When the social media usage score is below 3.8, each unit increase in the social media score corresponds to a decrease of 0.12 in the internet health trust score (95% CI: -0.19 to -0.05, P < .001). Conversely, when the application usage score is 3.8 or above, each unit increase leads to an increase of 0.46 in the internet health suggestibility score (95% CI: 0.42 to 0.50, P < .001). Interaction analysis revealed significant interactive factors affecting the relationship between social media usage frequency and suggestibility by internet health information, including gender (P = .045), age (P < .001), body measurement index (P = .03), sleep latency (P = .001), self-monitoring of blood glucose frequency (P = .001), and glycemic control status (P < .001).

Once a certain threshold of social media usage frequency is reached, suggestibility by internet health information cues increases with increased usage. Monitoring social media usage frequency could thus provide insightful indicators for evaluating the online behavioral and psychological profiles of individuals engaged in online blood glucose management.

Patients with diabetes are at an increased risk of cardiovascular disease (CVD), including atherosclerotic CVD and heart failure. In addition, diabetes is associated with a higher risk of developing chronic kidney disease, which is considered to be one of the strongest risk factors for CVD and mortality. To address the increased cardiovascular risk of patients with diabetes, dedicated screening strategies for CVD are necessary; conversely, screening for diabetes needs to be performed in all patients with CVD to allow timely identification. Once diabetes is diagnosed, rapid implementation of treatment with therapies to reduce cardiovascular risk on top of standard of care is necessary. This review gives an overview of contemporary therapeutic strategies to reduce cardiovascular risk in patients with type 2 diabetes.

To compare the effects of switching from dipeptidyl peptidase 4 (DPP-4) inhibitors to oral semaglutide on oxidative stress and glucose variability assessed by continuous glucose monitoring in patients with type 2 diabetes mellitus (T2DM).

This was an open-label, prospective, randomized, multicenter, parallel-group comparison study conducted over 24 weeks. Patients with T2DM who had been taking regular doses of DPP-4 inhibitors for at least 12 weeks were enrolled. They were randomly assigned to either continue on DPP-4 inhibitors (DPP-4 inhibitor group) or switch to oral semaglutide at 3 mg/day, with a dose increase to 7 mg/day after 4 weeks (semaglutide group). The primary endpoint was the change in the diacron-reactive oxygen metabolites test, an oxidative stress marker. Secondary endpoints included changes in glucose variability assessed using continuous glucose monitoring, metabolic indices, physical assessments, and Diabetes Treatment Satisfaction Questionnaire scores.

Fifty-eight patients with T2DM were randomized to the semaglutide group (n = 30) and the DPP-4 inhibitor group (n = 28). Six patients in the semaglutide group and one patient in the DPP-4 inhibitor group dropped out during the study. Ultimately, data from 24 patients in the semaglutide group and 27 patients in the DPP-4 inhibitor group were included for analysis. Switching to oral semaglutide therapy for 24 weeks significantly reduced oxidative stress, glucose variability, and hemoglobin A1c levels compared to continuous treatment with DPP-4 inhibitors. However, there was no significant difference in Diabetes Treatment Satisfaction Questionnaire scores between the two groups.

Our study demonstrated that switching to oral semaglutide therapy from DPP-4 inhibitors significantly improved oxidative stress and glycemic parameters, including glucose variability, in patients with T2DM.

jRCT1031210620.

Objective Although chronic kidney disease (CKD) is independently associated with hypertension or hyperglycemia, there is no consensus on the thresholds of obesity, dyslipidemia, or visceral fat accumulation to predict CKD onset and progression. Methods We performed a multivariable logistic regression analysis for the association of the subsequent rate of estimated glomerular filtration rate (eGFR) decline with body mass index (BMI), blood high-density lipoprotein (HDL) cholesterol and triglycerides (TG) levels on 308,174 subjects who underwent health examinations conducted by the Public Health Research Center Foundation from 2015 to 2022. In addition, a Poisson regression analysis was used to evaluate the association between the appearance of urinary protein in participants without baseline urinary protein levels and eGFR decline. Results The median age of the subjects was 46 years old, and the median observation period was approximately 3 years. An eGFR decline rate of ≥5%/year was significantly associated with low HDL-cholesterol levels (<40 mg/dL), independent of the BMI and TG levels. A high baseline BMI (≥25 kg/m2) or waist circumference (≥85 cm for men and ≥90 cm for women), high TG levels (≥150 mg/dL), and low HDL-cholesterol levels were significantly associated with new-onset proteinuria. Furthermore, the higher the baseline BMI, the higher the incidence rate ratio of new-onset proteinuria. Conclusion Independent of hyperglycemia and hypertension, dyslipidemia according to the Japanese metabolic syndrome criteria and an elevated BMI were associated with a high risk of new-onset proteinuria, and a low HDL-cholesterol level was significantly associated with a rapid eGFR decline.

Obesity is associated with both high and low levels of hypoglycemia, and impairment of counterregulatory hormones may predispose individuals to hypoglycemia. This study aimed to explore differences in the responsiveness of insulin counterregulatory hormones to hypoglycemia between men with or without obesity who have been newly diagnosed with type 2 diabetes mellitus (T2DM). This study enrolled 25 men newly diagnosed with T2DM who were hospitalized in the Department of Endocrinology and Metabolism between January 2022 and December 2022. All participants were treated with intensive insulin pump therapy to achieve glycemic control within one week, then a hyperinsulinemic-hypoglycemic clamp was used to evaluate insulin counter-regulatory hormones for hypoglycemia. Based on the body mass index, 10 and 15 patients were included in the obese and nonobese groups, respectively. During the hyperinsulinemic-hypoglycemic clamp test, the obese group showed a significant lower multiple of adrenocorticotropic hormone elevation than the nonobese group (P = 0.040). Regarding the proportion of hormone response multiples reaching the target, those who reached the reaction multiple were lower in the obese group than those in the non-obese group, although the differences were not statistically significant (all P > 0.05). The responses of insulin counterregulatory hormones to hypoglycemia in men with obesity and newly diagnosed T2DM were significantly lower than those in men with T2DM but without obesity.

Despite the recognition by key guidelines that achieving early glycaemic control has important benefits in individuals with type 2 diabetes (T2D) and that addressing excess adiposity is one of the central components of comprehensive person-centred T2D care, a substantial proportion of individuals with T2D do not meet their metabolic treatment goals. Prior treatment paradigms were limited by important treatment-associated risks such as hypoglycaemia and body weight gain. Therefore, a more conservative, sequential approach to treatment was typically utilized. One potential consequence of this approach has been a missed opportunity to achieve a 'legacy effect', where early treatment to reach glycaemic targets is associated with enduring long-term benefits in T2D. Additionally, while previous treatment approaches have addressed core defects in T2D, including insulin resistance and β-cell function decline, they have been unable to address one of the underlying causal abnormalities-excess adiposity. Here, we review currently available evidence for the beneficial long-term effects of early glycaemic control and management of body weight in people with T2D and discuss potential next steps.

Glucagon-like peptide-1 (GLP-1) receptor agonists represent efficacious therapies for treating type 2 diabetes. Oral semaglutide is the only orally administered GLP-1 receptor agonist currently available and has been associated with reductions in glycated hemoglobin and body weight versus once-daily injectable liraglutide after 52 weeks in the PIONEER 4 clinical trial. As lower-cost liraglutide formulations have recently been developed, the present analysis evaluated the long-term cost-effectiveness of oral semaglutide 14 mg versus liraglutide 1.8 mg at lower acquisition costs in the UK.

The published and validated PRIME Type 2 Diabetes Model was used to project clinical and cost outcomes over patient lifetimes. Baseline cohort characteristics, as well as treatment-specific changes in physiological parameters and hypoglycemia rates, were sourced from PIONEER 4. Patients were modeled to receive oral semaglutide or liraglutide until HbA1c exceeded 8.0% (64 mmol/mol), after which treatment was intensified to basal insulin. Annual disutilities associated with treatment administration were applied to capture the differential impact of a once-daily oral versus once-daily injectable medication on quality of life. Costs, expressed in 2022 pounds sterling (GBP), were calculated from a National Health Service (NHS) perspective. The acquisition cost of liraglutide was reduced by up to 50% at increments of 5% across a range of scenarios.

Oral semaglutide was associated with improved quality-adjusted life expectancy of 0.18 quality-adjusted life years versus liraglutide 1.8 mg due to a reduced incidence of diabetes-related complications and a reduced treatment-administration burden. Direct, per-person complication costs were estimated to be GBP 187 lower with oral semaglutide. Oral semaglutide remained dominant or cost-effective in the majority of scenarios, even with liraglutide price reductions of 50% applied.

Oral semaglutide 14 mg was projected to be cost-effective versus lower-cost liraglutide 1.8 mg in the UK.

Chronic kidney disease (CKD) represents one of the most significant risks for death, in patients with existed cardiovascular disease (CVD). This study aimed to investigate whether the excess risk of death in these patients could be reduced or eliminated through joint intensive control of blood pressure, glucose and renin-angiotensin system inhibitors (RASi) treatment, among CVD patients with CKD.

Overall, 6222 CVD patients with CKD and 9274 matched CVD patients who were free of CKD, hypertension and diabetes from CIN II cohort (NCT05050877), were included in the study. The association of all-cause and cardiovascular mortality with guideline-directed management was detected by Cox proportional hazards regression analysis.

During 5.6-year median follow-up, 3076 (19.9 %) patients died and 1578 (10.2 %) for cardiovascular cause. Among patients with CKD, risk factor controls and treatment were associated with a reduction in the risk of all-cause and cardiovascular mortality. Furthermore, compared to the non-CKD patients, both risk factors within the target ranges plus RASi therapy could theoretically eliminate the excess risk of all-cause (1-year: adjusted hazard radio [aHR] = 0.79, 95 % CI: 0.39-1.63; long-term: aHR = 0.99, 95 % CI: 0.73-1.34) and cardiovascular (1-year: aHR = 1.26, 95 % CI: 0.82-1.93; long-term: aHR = 1.15, 95 % CI: 0.75-1.76) mortality associated with CKD in stage 3a patients. Similar results were observed in patients at CKD stage 3 b.

CVD Patients with early CKD who had controlled blood pressure, glucose and took RASi therapy showed no excess risk of all-cause and cardiovascular death compared to the those without CKD.

Reduction of major atherosclerotic cardiovascular events (MACE) has not been consistent among different glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to assess the association between the magnitude of glycemic control, body weight loss, and reductions in systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) achieved through GLP-1 RA therapy and MACE.

Electronic databases (MEDLINE, CENTRAL, SCOPUS) were searched through March 2023. Studies were eligible if they were cardiovascular outcome trials (CVOTs) comparing GLP-1 RAs versus placebo in T2DM patients. The outcome of interest was 3-point MACE - cardiovascular death, myocardial infarction, or stroke. Random-effects meta-regression analyses evaluated the associations between reductions of HbA1c, body weight, SBP and LDL-C and reduction of MACE.

Overall, 8 CVOTs were included (60079 patients, 30693 with GLP-1 RAs). Reductions of HbA1C were associated with the reduction of 3P-MACE (Log RR -0.290 [95% CI -0.515;-0.064], p = 0.012), with an estimated RR reduction of 25% for each 1% absolute reduction in HbA1C levels. Body weight loss was associated with the reduction of 3P-MACE (Log RR -0.068 [95% CI -0.135;-0.001], p = 0.047), with an estimated RR reduction of 7% for each 1 kg reduction in body weight. Reductions of SBP (Log RR -0.058 [95% CI -0.192;0.076], p = 0.396) and LDL-C (Log RR -0.602 [95% CI -4.157;2.953], p = 0.740) were not associated with the reduction of 3P-MACE.

In T2DM patients, more potent GLP-1 RAs in reducing HbA1c and body weight were associated with greater reductions of MACE.

Diabetic cardiomyopathy (DC) is a serious complication of diabetes, characterized by myocardial fibrosis, hypertrophy, oxidative stress, and inflammation. Perillaldehyde (PAE), a natural monoterpene, has shown potential in mitigating cardiac damage.

This study aims to elucidate the molecular mechanism of the protective effect of PAE on the DC and the interaction between DC pathogenesis.

Network pharmacology and molecular docking were used to identify PARP1 as a core target for PAE in DC. Animal experiments involved intervening DC mice with PAE and assessing cardiac function, oxidative stress, and apoptosis. In vitro, high glucose-induced H9c2 cells were used to validate PAE's effects on cell viability and protein expression.

The results showed that PAE improved the general condition of DC mice, reduced cardiac injury and cardiac insufficiency, decreased myocardial mitochondrial damage, and reduced apoptosis. In addition, PAE upregulated the expression of Bcl-2, downregulated Bax protein expression, inhibited Caspase-3 activity, and inhibited the expression of PARP1, TRPM2, CaN, and CaMKII proteins in DC mice and high glucose-induced H9c2 cells.

Mechanically, this study clarified that PAE's inhibition of the PARP1-TRPM2-CaMKII/CaN pathway reduces calcium-activated mitochondrial damage, apoptosis, and oxidative stress in diabetic cardiomyopathy. This discovery provides an innovative therapeutic strategy for DC and an experimental foundation for PAE's drug development, with significant practical implications.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to improve renal and cardiovascular outcomes in patients with type 2 diabetes. Limited evidence exists about the efficacy and safety of SGLT2 inhibitors in patients with frailty.

This was a post hoc pooled, participant-level data analysis of the CANVAS Program (CANVAS and CANVAS-R) and the CREDENCE trial. We examined the effect of canagliflozin on: (1) Major adverse cardiovascular events (MACE), (2) Cardiovascular mortality, (3) all-cause mortality, and (4) key safety outcomes. Frailty was defined by a Frailty Index (FI) based on a deficit accumulation approach (FI > 0.25: frail). Cox proportional-hazard models were used to estimate the efficacy and safety of canagliflozin overall and according to frailty status.

There were 14,543 participants (10,142 from the CANVAS Program, 4401 from the CREDENCE trial). Their mean age was 63.2 years; 35.3% were female. Frailty was present in 56% of the study participants. The benefits of canagliflozin were observed in both the frail and non-frail subgroups: HRs for MACE 0.80 (95% CI 0.70-0.90) in the frail versus 0.91 (95% CI 0.75-1.09) in the non-frail (p for interaction = 0.27); HRs for cardiovascular mortality 0.79 (95% CI 0.67-0.95) in the frail versus 0.94 (95% CI 0.70-1.27) in the non-frail (p for interaction = 0.38); HRs for all-cause mortality 0.81 (95% CI 0.70-0.94) in the frail versus 0.93 (95% CI 0.74-1.16) in the non-frail (p for interaction = 0.39). Adverse events were similar among frail and non-frail participants, except for osmotic diuresis (HRs 1.67, 95% CI 1.22-2.28 in the frail vs. 3.05, 95% CI 2.13-4.35 in the non-frail, p for interaction = 0.01).

Canagliflozin improved cardiovascular and mortality endpoints in participants with type 2 diabetes irrespective of frailty status, with a similar safety profile. Our findings, in addition to those from other recent studies, provide evidence to support the introduction of SGLT2 inhibitor therapy in patients perceived to be frail.

ClinicalTrials.gov CANVAS: NCT01032629; CANVAS-R: NCT01989754; CREDENCE: NCT02065791.

The hemoglobin glycation index (HGI) represents the difference between the observed and predicted values of haemoglobin A1c (HbA1c). However, the association between HGI and prognosis of heart failure (HF) is not completely clarified yet and requires more investigation. This study aimed to explore the connection between HGI and mortality in HF patients.

The data for the study were derived from the MIMIC-IV database from 2008 to 2019, a publicly available clinical database in intensive care. A linear regression equation between HbA1c and fasting blood glucose (FBG) was established to calculate predicted HbA1c. The endpoints were 30-day and 365-day all-cause mortality. Kaplan-Meier analysis was utilized to compare survival rates across groups differentiated by their HGI levels. The Cox regression models and restricted cubic spline (RCS) analysis were utilized to analyze the association between HGI and mortality.

The study collected a total of 2846 patients with HF (40.1% male), of whom 305 patients (10.7%) died within 30 days and 954 patients (33.5%) died within 365 days. Kaplan-Meier curves revealed patients with higher HGI had significantly higher mortality risks (log-rank P < 0.001). A high HGI was significantly associated with 30-day mortality (adjusted HR [aHR]: 2.36, 95% CI: 1.74-3.20, P < 0.001) and 365-day mortality (aHR: 1.40, 95% CI: 1.16-1.68, P < 0.001) after adjustment for potential confounders. Likewise, each unit increase in the HGI correlated with a 1.42-fold higher risk of 30-day mortality (aHR: 1.42, 95% CI: 1.28-1.57, P < 0.001) and 1.19-fold higher risk of 365-day mortality (aHR: 1.19, 95% CI: 1.11-1.68, P < 0.001). RCS analysis suggested an L-shaped nonlinear association between HGI and clinical endpoints (P for nonlinearity < 0.001), with an inflection point value of - 1.295. Subgroup analysis and sensitivity analysis revealed that the correlation between HGI and 30-day and 365-day all-cause mortality remained consistent.

In ICU-admitted HF patients, HGI was independently associated with increased risks of 30-day and 365-day mortality and the identification of high HGI (> 0.709) provided a valuable tool for clinicians to detect high-risk populations. Integrating HGI into routine clinical practice might strengthen the prognosis-based decision making improve HF patient outcomes.

This paper reviews the existing literature on lipidomics as a tool for improved cardiovascular risk estimation in both primary and secondary prevention populations.

Detailed lipidomic signatures identified by mass spectrometry have been shown to enhance risk estimation for clinical CAD and the presence of subclinical CAD on CTCA in multiple large cohort populations. In patients with established atherosclerotic disease, ceramide and phospholipid-based risk scores improve prediction for recurrent cardiovascular events and cardiovascular death. Lipidomic profiles and lipidomic-enhanced risk scores have been shown to improve prediction of incident cardiovascular disease, recurrent cardiovascular events and cardiovascular death independent of traditional risk factors. Simplified risk scores utilizing the ratios of several ceramide species improve clinical utility, however resources and infrastructure limit widespread implementation. There are currently no therapeutics to address lipidomic risk aside from traditional risk factor modification.

Zhigancao Decoction (ZGCD) is derived from "Treatise on Febrile Diseases" and is traditionally prescribed for treating a variety of cardiovascular conditions. As of now, there are no data to support its use as a treatment for diabetic cardiomyopathy (DCM) and the mechanism behind the effect is unclear as well. In the present study, clinical evidence for the efficacy of ZGCD in patients with DCM was examined using a meta-analysis and its underlying anti-DCM molecular mechanisms were explored via network pharmacology.

The current study utilized an extensive search strategy encompassing various domestic and foreign databases databases to retrieve pertinent articles published up to June 2024. In light of this, a thorough evaluation of the benefits and safety of Zhigancao decoction (ZGCD) was conducted in this study using RevMan and Stata. Subsequently, a number of active compounds and target genes for ZGCD were gathered from the TCMSP and BATMAN-TCM databases, while the main targets for DCM were obtained from databases such as GenCards, OMIM, TTD, and DrugBank. To select core genes, protein-protein interaction networks were generated using the STRING platform, and enrichment analyses were completed using the Metascape platform.

Meta-analysis results were ultimately derived from 9 studies involving 661 patients in total. In comparison with WM therapy alone, the pooled results showed that ZGCD significantly enhanced overall effectiveness. Additionally, the utilization of ZGCD was leading to a reduction in LVEDV, LVESV and LVDD, also a greater increase in LVEF. Meanwhile, the utilization of ZGCD during intervention was more effective in reducing SBP, and DBP. In addition, the ZGCD showed potential in reducing the occurrence of adverse events. In the context of network pharmacology, five constituents of ZGCD-namely lysine, quercetin, gamma-aminobutyric acid, stigmasterol, and beta-sitosterol-are posited to exert anti-diabetic cardiomyopathy (anti-DCM) effects through interactions with the molecular targets ASS1, SERPINE1, CACNA2D1, AVP, APOB, ICAM1, EGFR, TNNC1, F2, F10, IGF1, TNNI2, CAV1, INSR, and INS. The primary mechanisms by which ZGCD may achieve its anti-DCM effects are likely mediated via the AGEs/RAGE signaling pathway, as well as through pathways related to lipid metabolism and atherosclerosis.

In comparison to WM therapy alone, ZGCD demonstrates greater efficacy and safety in the management of DCM. ZGCD not only significantly reduces blood pressure, but also enhances cardiac function while producing fewer adverse effects. The therapeutic effects of ZGCD on DCM can likely be ascribed to its capacity to modulate the AGEs-RAGE signaling pathway, as well as its efficacy in enhancing lipid metabolism and mitigating atherosclerosis.

identifier (INPLASY202430133).

Diabetes mellitus is a global public health issue, often leading to organ damage, complications, and disabilities. Frailty is an age-related syndrome characterized by reduced physiological reserve and increased vulnerability to stressors, significantly affecting the prognosis of older diabetic patients. The prevalence of frailty is notably higher in older adults with diabetes than in those without. Therefore, a bibliometric analysis of research on diabetes-related frailty can provide deeper insights into the current state of this field and inform future research directions.

This study retrieved English-language publications on diabetes-related frailty from the Web of Science Core Collection (WOS) database, covering the period from 2005 to 2023. A total of 403 articles were included in the analysis. Statistical analysis and data visualization were conducted using Microsoft Excel, R Studio, VOS viewer, and Cite Space 6.3.R1. The analysis emphasized journals, authors, keywords, country collaborations, institutional collaborations, and references to elucidate trends and knowledge structures within the field of diabetes-related frailty research.

The number of publications on diabetes-related frailty has been steadily increasing each year, with research predominantly focused in developed countries, particularly the United States and Europe. The University of London has emerged as the institution with the highest volume of publications, while Alan J. Sinclair has been recognized as a significant contributor to this field. Key research hotspots include the complications associated with diabetes-related frailty, epidemiology, and quality of life. Additionally, a timeline analysis of references suggests that diabetic nephropathy is currently at the forefront of research in this area.

This comprehensive bibliometric analysis of diabetes-related frailty research underscores the necessity for improved international collaboration to further investigate the mechanisms underlying diabetes-related frailty and to devise more effective prevention and treatment strategies. Future research should emphasize the relationship between diabetic nephropathy and frailty, as well as the development of personalized intervention programs tailored for frail diabetic patients.

Background/Objectives: Continuous and flash glucose monitoring (CGM and FGM) may enhance glucose management by providing real-time glucose data. Furthermore, growing evidence is linking altered blood glucose concentrations and worse short-term outcomes in critically ill patients. While hyperglycemia is more common in these patients and is associated with an increased risk of adverse events, hypoglycemia is particularly concerning and significantly raises the risk of fatal outcomes. This exploratory study investigated the link between FGM variables and cardiogenic shock in critically ill Coronary Care Unit (CCU) patients. Methods: Twenty-eight CCU patients (1 May 2021-31 January 2022) were monitored using a Libre FreeStyle system. Analyzed data included patient demographic and laboratory data, left ventricular ejection fraction, standard glucose monitoring, APACHE IV scores, and cardiogenic shock occurrence. Analysis was performed using the χ2 test, Mann-Whitney U test, and logistic regression. Results: Among the patients, 13 (46.43%) developed cardiogenic shock. FGM detected hypoglycemia in 18 (64.29%) patients, while standard methods in 6 (21.43%) patients. FGM-detected hypoglycemia was more frequent in patients who developed cardiogenic shock (p = 0.0129, χ2 test) with a significantly higher time below range reading (p = 0.0093, Mann Withney U test), despite no differences in mean glucose values. In addition, hypoglycemia detected by FGM was an independent predictor of shock (p = 0.0390, logistic regression). Conclusions: FGM identified more hypoglycemic events compared to standard glucose monitoring in the CCU. Frequent FGM-detected hypoglycemic events were associated with cardiogenic shock, regardless of a history of diabetes. Due to a limited sample size, these results should be interpreted cautiously and further research in this area is justified.

The community health workers (CHWs)-led model is an important strategy for managing type 2 diabetes mellitus (T2DM) in China. However, existing community-based dietary and health education interventions in diabetes management are insufficient. Meanwhile, emerging mobile health (mHealth) has emerged as a promising tool for improving disease management. Current evidence on the combined efficacy of mHealth technologies and CHWs strategies remains limited.

This study evaluates the effectiveness of an online dietary and health education intervention delivered through a tertiary hospital's WeChat official account (WOA) for T2DM patients, examining its influence on glycated hemoglobin (HbA1c) levels, body mass index (BMI), serum lipid profiles, and diabetes-specific quality of life (DSQL).

This randomized clinical trial was conducted in two community health centers in China, enrolling adults diagnosed with T2DM. Participants were randomly assigned to two groups over 3 months. The control group received standard care, while the intervention group accessed online low glycaemic index (GI) dietary and lifestyle recommendations via the WOA. This group was instructed to monitor blood glucose levels, upload daily dietary photos, review health education notifications, and participate in real-time communication with the diabetes management team via the WOA.

A total of 178 participants were randomized to the control group (mean [SD] age, 57.07 [10.96] years, n = 89) and the intervention group (mean [SD] age, 57.18 [10.61] years, n = 89). After 3 months, significant improvements were observed in the intervention group compared to the control group, with lower HbA1c levels (mean 7.82%, SD 0.43%; p = 0.001), BMI (mean 24.35, SD 1.25 kg/m2; p < 0.001), low-density lipoprotein cholesterol (mean 2.38, SD 0.21 mmol/L; p < 0.001), and DSQL scores (mean 43.24, SD 7.23; P < 0.001), whereas high-density lipoprotein cholesterol (mean 1.35, SD 0.37 mmol/L; p = 0.001) was significantly higher. Subgroup analysis at 3 months showed that age, education, disease duration, comorbidity, and BMI influenced the effectiveness of HbA1c reduction.

Overall, the WOA-based intervention effectively engages patients in community diabetes management, leading to improved glycemic control, weight reduction, lipid metabolism optimization, and better quality of life.

ChiCTR2400081045.

This expert consensus reviews the reality of primary care clinical management of people with type 2 diabetes (T2D) on non-intensive insulin therapy, with an emphasis on the use of continuous glucose monitoring (CGM) technology for effective care in this participant group. Here, we identify key unmet needs for skills and systems development within this frontline healthcare setting, along with major challenges and opportunities associated with managing these changes effectively.

The authors participated in two primary care consensus panels held on 28 November 2023 and on 21 May 2024. The focus for these expert panels was to understand the unmet needs within primary care to manage adults with T2D treated with non-intensive insulin therapy and incorporating the use of CGM systems. A Delphi Survey was undertaken among a wider group of Primary Care Diabetes Technology Network members in the United Kingdom, to understand prevalent attitudes to management of adults with T2D on insulin and using CGM in primary care. Based on these activities, a series of consensus statements were tested in a second Delphi Survey.

The activities described, involving primary care healthcare professionals (HCPs) with expertise in diabetes management, identified a series of training and educational needs within UK general practice that are central to skills development for the care of adults with T2D on insulin therapy and the application of CGM technology. Potential barriers to effective primary care management of people with T2D using CGM devices were identified. Areas of concern included confidence in national and local guidelines for the management of T2D using CGM systems, lack of experience on the part both of HCPs and people with T2D, clinical workflows and systems, as well as inbuilt resistance to change among primary care teams. However, the expert group were clear that the goal of providing care for people with T2D on non-intensive insulin therapy using CGM technology as standard of care could be met (94.3%, n = 33). This will deliver clinical benefits for people with T2D, and improvements to clinical workflows in primary care. Cost-savings to the health service were also identified as an outcome.

The need to adapt to the management of people with T2D on insulin therapy puts significant pressure on current workflows and skills for primary care teams. Steps in overcoming these immediate pressures, to ensure effective clinical management of people with T2D, are discussed, along with a series of consensus statements that identify the key areas of change to manage. Ultimately, the great majority of expert primary care HCPs were confident or very confident that using CGM technology will become the standard of care for people with T2D treated with insulin in primary care.

The ACCORD trial showed that intensive glucose-lowering therapy has a limited impact on renal function decline. We aimed to identify subgroups in the ACCORD population that might derive renal benefits from intensive glucose-lowering therapy.

The primary renal outcome included a ≥50% decline in baseline estimated glomerular filtration rate or end-stage renal disease (ESRD). Using the causal tree model, we employed internal cross-validation to identify five pivotal variables influencing the renal efficacy of intensive glycaemic control. These variables were integrated into the model-based recursive partitioning approach, yielding a visualizable tree model that depicted benefitting subgroups.

Node 4, characterized by no cardiovascular history, systolic blood pressure (SBP) ≤142.67 mm Hg, and triglycerides ≤172 mg/dL, showed significantly reduced hazards of the composite renal outcome (fully adjusted hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.49-0.89; p = 0.006) and doubling of serum creatinine (fully adjusted HR 0.59, 95% CI 0.36-0.98; p = 0.041). Node 7 (no cardiovascular history and SBP 142.67-154 mm Hg) showed reduced hazards of the primary renal outcome (fully adjusted HR 0.67, 95% CI 0.49-0.93; p = 0.016) and ESRD (fully adjusted HR 0.35, 95% CI 0.17-0.74; p = 0.0057). Encouragingly, neither node 4 nor node 7 displayed elevated cardiovascular risk or hypoglycaemic events.

Through innovative machine learning, we identified ACCORD subgroups benefitting significantly from intensive glycaemic therapy for renal outcomes, without increased cardiovascular or hypoglycaemic risks.

Vascular endothelium is integral to the regulation of vascular homeostasis and maintenance of normal arterial function in healthy individuals. Endothelial dysfunction is a significant contributor to the advancement of atherosclerosis, which can precipitate cardiovascular complications. A notable correlation exists between diabetes and endothelial dysfunction, wherein chronic hyperglycemia and acute fluctuations in glucose levels exacerbate oxidative stress. This results in diminished nitric oxide synthesis and heightened production of endothelin-1, ultimately leading to endothelial impairment. In clinical settings, it is imperative to implement appropriate therapeutic strategies aimed at enhancing endothelial function to prevent and manage diabetes-associated vascular complications. Various antidiabetic agents, including insulin, GLP-1 receptor agonists, sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, α-glucosidase inhibitors, thiazolidinediones (TZDs), and metformin, are effective in mitigating blood glucose variability and improving insulin sensitivity by lowering postprandial glucose levels. Additionally, traditional Chinese medicinal compounds, such as turmeric extract, resveratrol, matrine alkaloids, tanshinone, puerarin, tanshinol, paeonol, astragaloside, berberine, and quercetin, exhibit hypoglycemic properties and enhance vascular function through diverse mechanisms. Consequently, larger randomized controlled trials involving both pharmacological and herbal interventions are essential to elucidate their impact on endothelial dysfunction in patients with diabetes. This article aims to explore a comprehensive approach to the treatment of diabetic endothelial dysfunction based on an understanding of its pathophysiology.