The relationship between low-density lipoprotein cholesterol (LDL-C) levels and bleeding risk during antiplatelet therapy post-percutaneous coronary intervention (PCI) is uncertain, and the effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on bleeding risk is unknown.

This retrospective cohort study analyzed data from 85,464 PCI patients on oral antiplatelet therapy across 82 Tianjin hospitals from 2017 to 2023, using 1:1 PSM. The primary outcome was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding within one year. Kaplan-Meier survival curves and Cox regression models were employed to assess the association between PCSK9i and clinical outcomes, with Win-ratio analysis used for composite endpoints.

Among 85,464 patients (64 % male), 1979 (2.32 %) received PCSK9i were followed for one year. After PSM, a balanced cohort of 1951 patients in both the PCSK9i and control groups was established. Multivariate cox regression analysis revealed that patients on PCSK9i had significantly reduced risks of NACE (aHR: 0.674, 95 %CI: 0.528-0.859, P = 0.001), MACCE (aHR: 0.674, 95 %CI: 0.524-0.866, P = 0.002), all-cause death (aHR: 0.501, 95 %CI: 0.275-0.915, P = 0.025), and revascularization (aHR: 0.604, 95 %CI: 0.419-0.872, P = 0.007) at one year. No significant differences were found in other endpoints. The hierarchical outcome significantly favored PCSK9i (matched win ratio 0.634, 95 % CI: 0.584-0.689, P < 0.001).

PCSK9i therapy did not increase bleeding risk and was associated with lower risks of adverse outcomes compared to the control group.

Type 2 diabetes is associated with a heightened risk of cardiovascular complications, including myocardial steatosis. Fasting-mimicking diets (FMDs) may mimic the metabolic benefits of fasting, while being less intensive than fasting. This study aims to investigate the effect of following an FMD program on myocardial triglyceride content (MTGC), as assessed by Magnetic Resonance Spectroscopy (MRS), in patients with type 2 diabetes.

100 patients with type 2 diabetes, who used metformin as the only glucose-lowering drug or no medication were randomly assigned to either an FMD group or a control group. The FMD group received the FMD program for 5 consecutive days a month alongside usual care, while the control group received usual care only. Both groups underwent baseline, 6-months and 12-months examinations, including single voxel cardiac 1H-MRS to assess MTGC. N = 13 participants of the FMD and n = 13 of the control group had complete data at baseline and twelve month follow-up. The FMD group exhibited a significant reduction in MTGC over the twelve month period (-0.235 % MTGC, p = 0.027), while the control group saw no significant change (0.143 % MTGC, p = 0.236). The decrease of MTGC in the FMD group was statistically different (p = 0.018) from control.

Following an FMD program reduces MTGC, which indicates a favorable effect on cardiac metabolism and thereby may be an effective strategy to reduce the cardiovascular risk in patients with type 2 diabetes.

NCT03811587.

ClinicalTrials.gov; NCT03811587, submitted January 13th, 2019.

Risk of premature atherosclerotic cardiovascular disease (ASCVD) attributable to diabetes is poorly understood. We evaluated the impact of diabetes on future risk of ASCVD in young men and women.

Observational cohort study of young adults (ages 30-55 years) without established ASCVD (as of January 1, 2006) who were members of Kaiser Permanente Northern California, an integrated healthcare delivery system. Adjusted demographics (age, race) and traditional risk factors (hypertension, LDL-cholesterol, HDL- C, total cholesterol, smoking). Models were specified to estimate risk ratios (RRs) for incident ASCVD events by diabetes status: no diabetes (reference) versus diabetes with no treatment, with oral hypoglycemic (OH) only and with OH plus insulin. Incident ASCVD events were defined as a composite of nonfatal myocardial infarction, ischemic stroke, or coronary heart disease death through December 31, 2020. In fully adjusted models, individuals with diabetes using insulin exhibited a 5-fold higher risk among women (RR: 5.44; 95 % CI: 4.90-6.05) and a 3-fold higher risk among men (RR: 3.13; 95 % CI: 2.84-3.45) for incident ASCVD events compared to those without diabetes.

A proactive stance towards ASCVD risk management in young individuals with diabetes, healthcare professionals can help improve the morbidity and mortality associated with this complex interplay of metabolic and cardiovascular disease.

The clinical significance of diabetes mellitus (DM) on the cardiovascular disease in the zero coronary artery calcium (CAC) group is not well studied. This study investigated the impact of DM in an asymptomatic population with zero CAC scores. Overall, 9269 adults who received coronary computed tomography angiography (CCTA) scans for coronary disease evaluation during a general medical checkup were initially selected. After excluding participants with CAC >0, 4139 were included in the analysis. Baseline characteristics, CCTA findings including significant stenosis ≥50%, and clinical outcomes were assessed, including all-cause death, cardiovascular death, myocardial infarction (MI), or revascularization. The average age was 51.8 years, and 2706 participants (65.3%) were male. DM group had a higher prevalence of noncalcified plaque (16.7% vs 11.6%), significant stenosis (3.4% vs 1.5%), and a greater atherosclerosis burden than the non-DM group. DM was identified as a significant predictor of significant stenosis (adjusted odds ratio 1.88 [1.07-3.33], p = 0.029). During the median follow-up of 5.3 years, participants with DM experienced a higher rate of revascularization (1.2% vs 0.3%, adjusted hazard ratio 3.64 [1.25-10.56], p = 0.018), with a remarkably low incidence of cardiovascular death (0% vs 0.1%) and MI (both 0%). The risk of significant stenosis and revascularization increased gradually according to the severity of DM. In conclusion, asymptomatic patients with DM and zero CAC scores may face an increased risk of coronary artery disease presence compared to non-DM individuals. Despite zero CAC suggesting a low risk of cardiovascular disease, patients with DM may still exhibit a demonstrable atherosclerotic burden.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the developed world. Although women generally have a lower prevalence, they have unique factors placing them at risk for CVD compared to their male counterparts. Studies show that prevention, early detection, and treatment can reduce downstream sequelae of CVD. However, sex and gender-specific recommendations are lagging and not always optimally disseminated to patients and providers. This article will explore sex and gender-based differences in cardiovascular burden of disease, risk factors, presentation, and natural history to aid in early identification and intervention.

BackgroundIschemic stroke is a critical neurological condition, with infection representing a significant aspect of its clinical management. Sepsis, a life-threatening organ dysfunction resulting from infection, is among the most dangerous complications in the intensive care unit (ICU). Currently, no model exists to predict the onset of sepsis in ischemic stroke patients. This study aimed to develop the first predictive model for sepsis in ischemic stroke patients using data from the MIMIC-IV database, leveraging machine learning techniques.MethodsA total of 2238 adult patients with a diagnosis of ischemic stroke, admitted to the ICU for the first time, were included from the MIMIC-IV database. The outcome of interest was the development of sepsis. Model development adhered to the TRIPOD guidelines. Feature selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, identifying 28 key variables. Multiple machine learning algorithms, including logistic regression, k-nearest neighbors, support vector machines, decision trees, and XGBoost, were trained and internally validated. Performance metrics were assessed, and XGBoost was selected as the optimal model. The SHAP method was used to interpret the XGBoost model, revealing the impact of individual features on predictions. The model was also deployed on a user-friendly platform for practical use in clinical settings.ResultsThe XGBoost model demonstrated superior performance in the validation set, achieving an area under the curve (AUC) of 0.863 and offering greater net benefit compared to other models. SHAP analysis identified key factors influencing sepsis risk, including the use of invasive mechanical ventilation on the first day, excessive body weight, a Glasgow Coma Scale verbal score below 3, age, and elevated body temperature (>37.5 °C). A user interface had been developed to enable clinicians to easily access and utilize the model.ConclusionsThis study developed the first machine learning-based model to predict sepsis in ischemic stroke patients. The model exhibited high accuracy and holds potential as a clinical decision support tool, enabling earlier identification of high-risk patients and facilitating preventive measures to reduce sepsis incidence and mortality in this population.

Immigrants in western countries face an increased risk of developing diabetes and have been shown to receive lower quality of diabetes care. However, it is uncertain whether this disparity in care persists when comparing immigrants and non-immigrants with similar levels of marginalization with respect to the social determinants of health.

Using population-based healthcare administrative data linked to immigration and neighbourhood census data, we conducted a retrospective cohort study of all people aged ≥ 40 years with diabetes in Ontario, Canada on 1 April 2019. Process measures (testing for HbA1c, LDL-cholesterol and urine albumin-creatinine ratio; eye examinations; and appropriate prescriptions) and outcome measures (achieving guideline-recommended targets for laboratory tests) over the following year were ascertained. They were compared between immigrants and non-immigrants overall and within the highest and lowest quintiles of three measures of marginalization: material deprivation, residential instability and dependency.

There were 1,449,589 people with diabetes included in the study (22.6 % immigrants). Immigrants were less likely than non-immigrants to achieve many of the process quality indicators and were less likely to achieve both HbA1c and LDL-cholesterol targets. These findings were similar when stratified within the highest and lowest quintiles of material deprivation, residential instability and dependency.

Even within similar levels of marginalization, immigrants were less likely to achieve many quality indicators for diabetes care than non-immigrants. This finding suggests that the gap in quality of care between immigrants and non-immigrants is not simply due to differences in these social determinants of health, and highlights the intersecting impact of immigration and marginalization. However, the disparities were relatively small, so the greater issue is the overall low achievement of these quality indicators among all people with diabetes.

The important effects of variability of some physiological/biological characteristics (such as LDL cholesterol, blood pressure) on cardiovascular outcomes have been elucidated, while the role of insulin variability is undefined.

To investigate the associations of long-term fasting insulin variability during young adulthood before the onset of diabetes with subsequent cardiovascular outcomes in middle age.

We included 3,983 CARDIA (Coronary Artery Risk Development Study in Young Adults) participants aged 18 to 30 years with at least three fasting insulin measurements. Intra-individual fasting insulin variability was defined by the average real variability (ARV) of insulin and standard deviation (SD) of insulin during 30-year follow-up. The presence and the degree of coronary artery calcification (CAC) were assessed by computed tomography at year 25. Incident cardiovascular disease (CVD) and all-cause mortality were adjudicated.

After multivariable adjustment, comparing high versus low tertile of insulin ARV, the hazard of CVD increased by 65 % (HR, 1.65; 95 % CI, 1.13-2.39) and all-cause mortality by 97 % (HR, 1.97; 95 % CI, 1.38-2.82). Higher tertile of insulin ARV was associated with significantly worse degree of CAC (β =0.1; 95 % CI, 0.03-0.18) but not with the presence of CAC (P = 0.197). Similar results were also observed in insulin SD.

High long-term insulin variability in young adulthood before the onset of diabetes was associated with an increased risk of CVD and all-cause mortality in later life, independent of average FG, HOMA-IR and other established cardiovascular risk factors. Long-term insulin variability was associated with the degree but not the presence of CAC.

Early menarche is associated with lifelong health implications, including heightened risks for obesity, type 2 diabetes (T2D), cardiovascular disease, and overall mortality. This study explored the associations that link early menarche, major adiposity indices, and T2D in a group of multi-ethnic Asian women.

A prospective, hospital-based study was conducted in Singapore. Two thousand seven hundred fifteen women were recruited from 2014 to 2016 (45-69 years old) and 1201 women were followed up from 2021 to 2023. At baseline, age at menarche (AAM) was divided into sub-categories: < 12 (early AAM), 12-13, 14-15 (reference), > 15 years. Major adiposity indices and glycemic profiles were assessed, including fat mass index (FMI), visceral adipose tissue (VAT), and HOMA-IR (homeostatic model assessment for insulin resistance). At the 6.6-year follow-up, T2D was assessed. One-way ANOVA and chi-square were performed for continuous and categorical variables, respectively. Multivariable regression analysis was performed to determine the association between AAM and primary outcomes, including adiposity measurements (FMI, VAT) and metabolic assessments (HOMA-IR) at baseline. Modified Poisson regression was performed to assess relative risk (RR) between AAM and T2D at follow-up. Serial mediation analysis was performed to determine potential mediators underlying the link between AAM and T2D. All analyses accounted for major confounders including age, ethnicity, and education.

Women with early AAM had significantly greater values in adiposity assessments, including increments in FMI (10.9 vs 10.3, p < 0.001), VAT (134 vs 113 cm2, p = 0.05) and HOMA-IR (1.20 vs 1.03, p = 0.08) at baseline. Early AAM (< 12 vs. 14-15 years) was associated with a 60% increased risk of developing T2D (RR 1.60 (95%CI: 1.04, 2.45)). Serial mediation analysis suggested a significant pathway underlying early AAM and T2D, which was firstly mediated by FMI, followed by VAT and lastly by HOMA-IR (p < 0.05).

Our study provided valuable insight into the pathophysiology of T2D development amongst mid-life women with early AAM. The findings could potentially indicate strategies to target FMI and VAT among Asian women in the menopausal phase with early AAM, to prevent the development of T2D.

Training can improve insulin sensitivity in individuals with type 2 diabetes, but a clear understanding of the mechanisms remains elusive. To further our knowledge in this area, we aimed to examine the effect of type 2 diabetes and of high-intensity interval training (HIIT) on the nuclear transcriptional response in skeletal muscle. We performed single-nucleus RNA-sequencing (snRNA-seq) and immunofluorescence analysis on muscle biopsies from the trained and the untrained legs of participants with and without type 2 diabetes, after 2 weeks of one-legged HIIT on a cycle ergometer. Surprisingly, the type 2 diabetes condition only seemed to have a minor effect on transcriptional activity in myonuclei related to major metabolic pathways when comparing the untrained legs. However, while in particular the type IIA myonuclei in the control group displayed a considerable metabolic response to HIIT, with increases in genes related to glycogen breakdown and glycolysis primarily in the type IIA myonuclei of the trained leg, this response was blunted in the diabetes group, despite a marked increase in glucose clearance in both groups. Additionally, we observed that fibre type distribution assessed by immunofluorescence significantly correlated with the proportion of myonuclei in the snRNA-seq analysis. In conclusion, the type 2 diabetes condition blunts the metabolic transcriptional response to HIIT in the type IIA myonuclei without affecting the improvement in insulin sensitivity. Additionally, our results indicate that snRNA-seq can be used as a surrogate marker for fibre type distribution in sedentary middle-aged adults. KEY POINTS: The study utilized single-nucleus RNA sequencing (snRNA-seq) to analyse 38 skeletal muscle biopsies, revealing distinct transcriptional profiles in myonuclei from individuals with and without type 2 diabetes (T2D) after 2 weeks of HIIT. snRNA-seq identified significant differences in gene expression, with 14 differentially expressed genes (DEGs) in type IIA myonuclei of the control group, specifically related to glycogen breakdown and glycolysis, which were blunted in the T2D group. In the control group, HIIT induced a substantial transcriptional response in type IIA myonuclei, enhancing metabolic pathways associated with insulin sensitivity, while the T2D group showed minimal transcriptional changes despite improved insulin sensitivity. The T2D group exhibited a blunted response in metabolic gene expression, indicating that the training effect on muscle adaptation was significantly impaired compared to healthy controls. Overall, the findings highlight the differential impact of HIIT on muscle metabolism, emphasizing the need for tailored exercise interventions for individuals with T2D.

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.

Menopause is a significant physiological transition characterized by hormonal changes that can influence cardiovascular health. One key concern is increased arterial stiffness, a predictor of cardiovascular disease and adverse cardiovascular events. However, the independent association between menopause and arterial stiffness, beyond traditional cardiovascular risk factors, remains unclear. This study investigates the relationship between menopause and arterial stiffness index in the women's UK Biobank cohort.

This cross-sectional study included 52,891 women from the UK Biobank with measurements of arterial stiffness index. Arterial stiffness index was assessed using a non-invasive photoplethysmographic method. Multiple linear and logistic regression models were used to examine the association between menopause status and arterial stiffness index (continuous and cutoff>10 m/s), adjusting for age, body mass index, antihypertensive medication use, income, education, dyslipidemia, alcohol consumption, chronic kidney disease, smoking, diabetes, heart rate, mean blood pressure, hormone therapy, and previous cardiovascular disease.

Postmenopausal women had significantly higher values of arterial stiffness index (9.10 ± 4.61 m/s) than premenopausal women (7.76 ± 2.72 m/s, p < 0.001). Menopause was independently associated with increased arterial stiffness index (B = 0.22, 95 % CI [0.16-0.28], p < 0.001) and a higher odds ratio for arterial stiffness index >10 m/s (OR = 1.41, 95 % CI [1.31-1.51], p < 0.001), after adjusting for confounders.

Menopause is significantly associated with increased arterial stiffness, independent of traditional cardiovascular risk factors. These findings highlight menopause as a critical period for cardiovascular health assessment and prevention strategies.

Diabetes increases the risk of several chronic conditions. However, their excessive prevalence among older adults with diabetes in Poland is unknown.

The prevalence of chronic diseases was assessed in the nationally representative random sample of 5,987 Polish adults aged 60+ (Polsenior2 study, data collected between 2018 and 2020). Each participant's history of hospitalisation due to coronary heart disease (CHD), stroke, and cancer was assessed. Diagnosis of arterial hypertension (AH), cognitive impairment (CI), and chronic kidney disease (CKD) was established based on the questionnaire, blood pressure measurements, Mini-Mental State Examination, and laboratory tests. Diabetes was diagnosed if the participant reported being diagnosed with the disease or their measured HbA1c was ≥ 48 mmol/mol (≥6.5%). Age- and sex-adjusted prevalence ratios of chronic conditions for participants with diabetes versus those without diabetes were calculated using Poisson regression.

In the multivariate model, the prevalence ratio for CHD history was 1.98 (95%CI: 1.66-2.37), for CKD: 1.90 (95%CI: 1.66-2.18), for stroke: 1.47 (95%CI: 1.15-1.88), for AH: 1.22 (95%CI: 1.17-1.27). Cancer and cognitive impairment prevalence did not differ between people with and without diabetes. The mean number of chronic diseases was 52% higher in participants with diabetes vs nondiabetic subjects at age 60-69 (1.72 (95%CI: 1.60-1.84) vs. 1.13 (95%CI: 1.07-1.18), respectively). However, this value was only 10% higher in subjects aged 90+ (2.74 (95%CI: 2.45-3.04) vs. 2.49 (95%CI: 2.37-2.62), respectively).

Elderly Polish citizens with diabetes suffer more often from coronary heart disease, stroke, chronic kidney disease, and arterial hypertension. The study emphasises that the excess prevalence of chronic diseases among people with diabetes is high in the youngest-old population but diminishes in the oldest-old people.

People living with type 2 diabetes (T2D) are at a two- to four-fold higher risk of developing cardiovascular disease (CVD) compared with those without T2D, making early assessment of their CV risk essential. European Society of Cardiology (ESC) has developed a new model to estimate 10-year CV risk in people with T2D aged ≥ 40 years: SCORE2-Diabetes. Despite its advantages, several aspects remain to be clarified. This study evaluated the association between CV risk stratified by SCORE2-Diabetes and early CV damage assessed through arterial stiffness, intima-media thickness (IMT), and carotid atherosclerosis. Additionally, it examined the agreement between risk stratification by SCORE2 and SCORE2-Diabetes and their concordance with vascular damage.

Pulse wave velocity (PWV), IMT, and carotid atherosclerosis were assessed in 179 individuals with T2D aged 40-69 years, categorized into SCORE2-Diabetes risk groups: Low (n = 20), Moderate (n = 29), High (n = 44), and very high (n = 37). Patients with a history of atherosclerotic cardiovascular disease (ASCVD) or severe target organ damage (TOD) constituted another group (ASCVD/TOD, n = 49).

PWV was significantly increased from Low to very high and ASCVD/TOD groups (7.2 ± 1.1, 8.7 ± 1.9, 9.8 ± 2.3, 12.8 ± 5.1 and 11.5 ± 3.8 m/s, respectively). Similarly, IMT showed a stepwise increase with risk class (0.68 ± 0.11, 0.78 ± 0.13, 0.83 ± 0.12, 0.86 ± 0.19 and 0.87 ± 0.15 mm, respectively). Patients in very high or ASCVD/TOD group showed a higher prevalence of carotid atherosclerosis than other groups (0%, 17.24%, 11.40%, 37.83% and 40.81%, respectively). No significant differences were found between the very high and ASCVD/TOD groups in any parameter. The correlation between PWV values and increasing CV risk was stronger for SCORE2-Diabetes than for SCORE2. ROC curve analysis showed SCORE2-Diabetes had superior predictive performance for carotid atherosclerosis and high PWV compared to SCORE2 (p = 0.048).

Higher PWV, IMT, and carotid atherosclerosis prevalence were associated with increasing CV risk stratified by SCORE2-Diabetes, with no significant differences between the very high and ASCVD/TOD groups. SCORE2-Diabetes demonstrated a better identification of preclinical vascular damage compared to SCORE2, supporting its use as a reliable tool for identifying vascular damage in T2D patients without ASCVD or TOD.

This study aimed to generate real-world data on the prevalence of cardiovascular disease (CVD), including atherosclerotic CVD (ASCVD) and heart failure (HF), as well as chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM) routinely treated in Greece.

This was a non-interventional, epidemiological, multicentre, cross-sectional and retrospective chart review study of T2DM patients attending a routine clinical visit at 198 outpatient primary care settings across Greece from November 2020 to February 2022.

Among 2000 enrolled T2DM outpatients, the prevalence of ASCVD was 20.40 % (95 % confidence interval [CI]: 18.67 %-22.25 %), of HF 8.03 % (95 % CI: 6.67 %-9.63 %), and of CKD 49.55 % (95 % CI: 47.36 %-51.74 %). Hypertension was correlated with increased risk of ASCVD, HF or CKD, dyslipidaemia with ASCVD and CKD, obesity solely with HF, and smoking with ASCVD. Patients over 65 years were at higher risk of ASCVD, HF or CKD, whereas those with T2DM for ≥10 years had a higher risk of ASCVD or HF. Finally, males were more likely to have ASCVD CONCLUSIONS: The present study confirms the high prevalence of CVD and CKD among Greek T2DM patients managed in primary care, that potentially qualify for new antidiabetic treatments with cardiovascular or renal benefits.

The burden of comorbid cardiovascular disease (CVD) and its preventable factors in type 2 diabetes is not well acknowledged in Ethiopia. Therefore, this study aimed to identify the magnitude of comorbidity of CVD and predictors among individuals with type 2 diabetes.

A multicentre hospital-based cross-sectional study.

Bahir Dar city Administration Public Hospitals, Ethiopia.

Data on comorbid CVDs among individuals with type 2 diabetes were collected through patient chart reviews. To identify predictors of CVDs in type 2 diabetes, information on lifestyle and psychosocial characteristics, medication and dietary adherence, and disease management status was collected using standardised questionnaires. Statistical analyses were performed using SPSS V.26. The level of statistical significance was set at p<0.05, with ORs and 95% CIs.

The participants' mean age (±SD) was 51.5±10.9 years. The overall prevalence of comorbid CVDs among type 2 diabetes was 27.9% (95% CI 23.6% to 32.3%). Factors that statistically predicted the occurrence of comorbid CVDs in type 2 diabetes were: age >60 years (adjusted ORs (AORs)=2.6, 95% CI 1.1 to 6.6), non-adherence to diabetes-friendly diet (AOR=4.0, 95% CI 1.9 to 8.2), low medication adherence (AOR=2.8, 95% CI 1.5 to 5.3), being overweight (AOR=5.3, 95% CI 2.9 to 9.8), and diabetes duration >10 years (AOR=3.7, 95% CI 1.7 to 8.1).

Comorbid cardiovascular disease is a significant issue among type 2 diabetic patients. Its prevalence is higher in patients over 60 years of age, with modifiable factors identified as key contributors. Appropriate interventions are recommended, including educating type 2 diabetic patients on dietary regimens, medication adherence, weight management, and the benefits of timely healthcare for effective disease management.

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.

Introduction: Hypertension is the most prominent established risk factor for adverse cardiovascular outcomes. The influence of hypertension in combination with other major cardiovascular disease risk factors (CVD-RFs) on mortality and cardiovascular events has not been fully comprehended yet due to their overlapping and interconnected nature. This study was conducted to evaluate the impact of CVD-RFs quantity on the occurrence of cardiovascular events, CVD-related mortality, and all-cause mortality rates in hypertensive patients. Design and Method: In a secondary analysis of the Isfahan Cohort Study, demographic information, anthropometric measures, and laboratory results of participants were extracted. During the 15 years of follow-up, all-cause mortality, CVD-related mortality, and the occurrence of nonfatal cardiovascular events were assessed by separate panels of experts. Data analysis was performed using Cox proportional hazard models to estimate adjusted hazard ratios (HRs) among normotensive and hypertensive individuals in two subgroups of 3 CVD-RFs and≥ 3 CVD-RFs. Results: Among 5432 eligible participants, hypertensive patients (n = 1509) had 1.3, 2, and 1.4 times higher HRs for all-cause mortality, CVD-related mortality, and nonfatal cardiovascular events, respectively. Compared to the normotensives, HRs for the mentioned outcomes were 1.2, 1.7, and 1.3 for hypertensive participants with < 3 CVD-RFs and 1.7, 3.4, and 2.3 for hypertensive participants with≥ 3 CVD-RFs. These rises were shown to be highly significant (p = 0.003, p = 0.001) for CVD-related mortality and nonfatal cardiovascular events in hypertensives with ≥ 3 CVD-RFs compared with hypertensives with < 3 CVD-RFs. Conclusions: Hypertension alone or combined with other CVD-RFs increases the chance of all-cause mortality, CVD-related mortality, and nonfatal cardiovascular events. Rises in the quantity of other CVD-RFs (specifically to≥ 3) result in highly significant increases in fatal and nonfatal cardiovascular events. Therefore, to reduce mortality and cardiovascular events, hypertensive patients should be thoroughly evaluated for coexisting CVD-RFs, aiming to limit the synergistic effects of multiple CVD-RFs by properly managing modifiable RFs.

Diabetes is associated with increased atherosclerotic cardiovascular disease (ASCVD) risk, a leading cause of morbidity and mortality. Disordered lipid metabolism is a major contributor to ASCVD risk in diabetes. Dyslipidemia in type 2 diabetes is characterized by hypertriglyceridemia, low high-density lipoprotein cholesterol and the presence of small, dense low-density lipoprotein particles. Statins have demonstrated longstanding benefit for reducing ASCVD risk in individuals with diabetes. Newer agents for add-on therapies to statins are now available for additional cardiovascular risk reduction. In this clinical overview, we review the pathogenesis of dyslipidemia in both type 1 and 2 diabetes and provide an update on the management of lipids in the individual with diabetes. We discuss the importance of appropriate risk stratification and individualized treatment selection and the need to avoid therapy inertia to mitigate cardiovascular risk. We also address lipid-related effects of glycemic-lowering therapies.

Adults with type 2 diabetes have an increased risk of cardiovascular events (CVEs), the world's leading cause of mortality. The SCORE2-Diabetes model is a tool designed to estimate the 10-year risk of CVE specifically in individuals with type 2 diabetes. However, the performance of such models may vary across different demographic and socioeconomic groups, necessitating validation and assessment in diverse populations. This study aims to externally validate SCORE2-Diabetes and assess its performance across various socioeconomic and migration origins in The Netherlands.

We selected adults with type 2 diabetes, aged 40-79 years and without previous CVE from the Extramural LUMC Academic Network (ELAN) primary care data cohort from 2007 to 2023. ELAN data were linked with Statistics Netherlands registry data to obtain information about the country of origin and socioeconomic status (SES). Cardiovascular event was defined as myocardial infarction, stroke, or CV mortality. Non-CV mortality was considered a competing event. Analyses were stratified by sex, Dutch vs. other non-Dutch countries of origin, and quintiles of SES. Of the 26 544 included adults with type 2 diabetes, 2518 developed CVE. SCORE2-Diabetes showed strong predictive accuracy for CVE in the Dutch population [observed-to-expected ratio (OE) = 1.000, 95% CI = 0.990-1.008 for men, and OE = 1.050, 95% CI = 1.042-1.057 for women]. For non-Dutch individuals, the model underestimated CVE risk (OE = 1.121, 95% CI = 1.108-1.131 for men, and OE = 1.100, 95% CI = 1.092-1.111 for women). The model also underestimated the CVE risk (OE > 1) in low SES groups and overestimated the risk (OE < 1) in high SES groups. Discrimination was moderate across subgroups with c-indices between 0.6 and 0.7.

SCORE2-Diabetes accurately predicted the risk of CVE in the Dutch population. However, it underpredicted the risk of CVE in the low SES groups and non-Dutch origins, while overpredicting the risk in high SES men and women. Additional clinical judgment must be considered when using SCORE2-Diabetes for different SES and countries of origin.

A new study validates the SCORE2-Diabetes model for predicting a 10-year risk of cardiovascular events in type 2 diabetes. Strong accuracy for the Dutch population, but underestimation of the risk for low SES and non-Dutch groups. SCORE2-Diabetes should be used with extra caution across diverse subgroups.

Diabetes, a metabolic disease that is becoming increasingly severe globally, presents a significant challenge in the medical field. Diabetic wounds are characterized by their chronicity, difficulty healing, and complex microenvironment that harbors multiple adverse factors, including elevated hyperglycemia, persistent inflammation, susceptibility to infections, and oxidative stress, all of which contribute to the impaired healing process. Nanocomposite hydrogels, as materials with unique physicochemical properties and biocompatibility, have gained growing attention in recent years for their potential applications in diabetic wound healing. These hydrogels provide a moist healing environment for wounds and regulate cellular behavior and signaling pathways, promoting wound repair and healing. By introducing specific functional groups and nanoparticles, nanocomposite hydrogels can respond to pathological features of wounds, enabling adaptive drug release. Owing to their diverse bioactive functions, nanocomposite hydrogels are powerful tools for the treatment of diabetic wounds. Thus, this article provides an overview of recent progress in the use of nanocomposite hydrogels for diabetic wound healing.

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.

This study contributes to develop and evaluate the biological applications of eco-friendly synthesized silver nanoparticles using Amphilophium paniculatum leaf ethanol extract via. solar irradiation method. The synthesized silver nanoparticles were characterized using UV, FTIR, FESEM and EDS. UV spectrum of silver nanoparticles showed the surface plasma resonance at 431 nm, which confirms the formation of silver nanoparticles. FTIR revealed the presence of functional groups in the extract which helps in the formation of silver nanoparticles. XRD pattern revealed the crystallite nature of nanoparticles. FESEM images showed spherical morphology with average size of 26-28 nm. Biological evaluations of silver nanoparticles exhibited higher antioxidant (IC50- 57.76 μg/mL) compared to extract (IC50- 100.09 μg/mL). The synthesized silver nanoparticles possess good antibacterial activities against clinical isolates such as Staphylococcus aureus (ZOI- 18 mm) and Klebsiella pneumonia (ZOI- 14 mm). Further, in vitro antidiabetic potential of silver nanoparticles revealed greater alpha amylase inhibition compared with standard drugs. The cytotoxic assessment on A549 cell lines revealed lower IC50 value (26.34 μg/mL) for silver nanoparticles, compared to extract (224 μg/mL), suggesting significant cytotoxicity. In silico screening of selected bioactive compounds from Amphilophium paniculatum evaluated for their physicochemical properties, toxicity and docking studies. Molecular docking studies revealed that (+)-lyoniresinol-3-alpha-O-beta-D-glucopyranoside and linarin exhibits better binding interactions with 2RIP-DPPIV receptor, suggesting a potent therapeutic agent for type 2 diabetes mellitus. Therefore, the synthesized silver nanoparticles act as multi therapeutic potential based novel drugs to combat multi-drug resistant pathogens, lung cancer, and diabetes mellitus.

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a pervasive chronic disease that affects millions of people worldwide. It predisposes individuals to a range of severe microvascular and macrovascular complications, which drastically impact the patient's quality of life and increase mortality rates owing to various comorbidities. This extensive review explores the intricate pathophysiology underlying diabetic complications, focusing on key mechanisms, such as atherosclerosis, insulin resistance, chronic inflammation, and endothelial dysfunction. It also highlights recent therapeutic advancements, including the introduction of SGLT2 inhibitors and GLP-1 receptor agonists, which provide benefits beyond glycemic control and offer cardiovascular and renal protection. Furthermore, the future position of SGLT2 inhibitors and GLP-1 receptor agonists in terms of the prevention of diabetes and macrovascular diseases will be discussed. Considering the differences in insulin secretion capacity between Western and Asian patients, including Japanese patients, we propose a treatment strategy for high-quality diabetes in Japan.

Type 2 diabetes is a major contributor to the burden of chronic diseases globally. Most cases of type 2 diabetes are preventable through healthy lifestyle modifications in diet and physical activity. This systematic umbrella review presents a comprehensive overview of the evidence about the associations between risk of type 2 diabetes and metabolic syndrome with 13 food groups, including refined and whole grains, fruits, vegetables, nuts, legumes, fish and fish products, eggs, dairy/milk, sugar-sweetened beverages, processed meat, and unprocessed red and white meat. We present these relationships in per-serving and with high-versus-low comparisons. After doing a systematic search in MEDLINE, Embase, Web of Science, and Epistemonikos (registered with PROSPERO: CRD42024547606), we screened 5074 references published until May 15, 2024, and included 67 articles. This included 46 meta-analyses on risk of type 2 diabetes with half a million participants, 17 meta-analyses on risk of metabolic syndrome, and 4 meta-analyses on risk of diabetes-related mortality. Based on quality assessments using AMSTAR-2, 25 of the 67 studies were classified as high-quality studies, 8 as moderate, 12 as low, and 22 as critically low quality. Our results showed that a high intake of whole grains was associated with a lower risk of type 2 diabetes (metaevidence: moderate) and metabolic syndrome (metaevidence: low), with a similar tendency also for a high intake of fruits and vegetables (metaevidence: moderate). In contrast, the high intakes of processed meat (metaevidence: high), red meat (metaevidence: moderate), and sugar-sweetened beverages (metaevidence: moderate) were associated with a higher risk of type 2 diabetes. For the other food groups, the associations were generally neutral and not statistically significant. The heterogeneity was high for most food groups except fruits, indicating potential differences within each of the food groups in association with type 2 diabetes.

Impaired angiogenic responses to ischemia underlie diabetic vascular complications. Reconstituted high-density lipoproteins (rHDLs) have proangiogenic effects in diabetes. The PDK4 (pyruvate dehydrogenase kinase 4)/PDC (pyruvate dehydrogenase complex) axis is an oxygen-conserving mechanism that preserves endothelial cell function in hypoxia. We aimed to determine the role of the PDK4/PDC axis in angiogenesis, the effect of diabetes on its regulation in response to ischemia, and the proangiogenic properties of rHDL.

Expression of PDK4 and phosphorylated PDC (pPDC) were measured in PBS- or rHDL-treated wounds of nondiabetic and streptozotocin-induced diabetic mice and PBS- or rHDL-treated endothelial cells exposed to glucose and hypoxia. The importance of PDK4 in the action of rHDL was determined by siRNA knockdown in vitro and PDK4 inhibitor in vivo. Chromatin immunoprecipitation assay was performed to identify the mechanism for PDK4 induction by rHDL.

PDK4 and pPDC were elevated early (24 hours) post-induction of wound ischemia in nondiabetic wounds, which did not occur in diabetic mice. Topical rHDL rescued this impairment, enhancing PDK4 (68%; P=0.0041) and pPDC (165%; P=0.029) in diabetic wounds. Wound neovascularization (62%; P<0.05) and closure (154%; P<0.001) were increased in diabetic rHDL-treated wounds. In vitro, PDK4 and pPDC levels were increased with hypoxia (65%, P=0.043 and 64%, P=0.026, respectively). High glucose did not elicit a further stepwise induction in PDK4/pPDC, with aberrant increases in mitochondrial respiration (19%; P=0.026), and impaired angiogenic functions. Importantly, rHDL increased PDK4 and pPDC 2-fold, returning mitochondrial respiration and angiogenic functions to normal glucose levels. PDK4 inhibition ameliorated the proangiogenic effects of rHDL. rHDL increased FOXO1 (forkhead box O1) binding to the PDK4 promoter and suppressed FOXO1 phosphorylation, presenting FOXO1 as a mechanism for rHDL-mediated induction of PDK4.

The PDK4/PDC axis response to ischemia is impaired in diabetes and is important for the proangiogenic effects of rHDL.

Patients with diabetes are considered to be at high surgical risk due to the potential occurrence of cardiovascular and diabetes-related complications. Limited research exists on the cardiovascular risk profiles of patients with prediabetes and undiagnosed diabetes in noncardiac surgery. In this population-based cohort study, we investigated different glycated hemoglobin levels and their associated postoperative cardiovascular risks.

In this perioperative cohort study, participants were categorized into four groups: nondiabetes, prediabetes, undiagnosed diabetes, and diagnosed diabetes. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE) at 30 days postoperatively, with secondary outcomes assessed at 90 days. The association between various groups and postoperative MACE was evaluated using Cox proportional hazards models and Kaplan-Meier curves. Subgroup analyses and sensitivity analyses were also performed.

We enrolled 13 207 eligible patients undergoing noncardiac surgeries, among whom 3841 (29.08%) had prediabetes and 1521 (11.52%) had undiagnosed diabetes. In the 30-day postoperative period, the prediabetes group (hazard ratio [HR] [95% CI]: 1.70 [1.15, 2.52]), undiagnosed diabetes group (HR [95% CI]: 2.36 [1.15, 3.68]), and diagnosed diabetes group (HR [95% CI]: 2.33 [1.54, 3.53]) exhibited increased risks of MACE compared to the nondiabetes group. Similar findings were observed for the 90-day postoperative MACE. Further subgroup analysis revealed a significant interaction between sex and states of glycemic regulation (P for interaction < 0.005).

In this cohort, a notable proportion of patients with prediabetes or undiagnosed diabetes were found to be undergoing noncardiac surgeries. They were associated with an increased risk of developing postoperative MACE.

Computed tomography perfusion (CTP) plays a crucial role in guiding reperfusion therapy and patient selection for acute ischemic stroke (AIS) through perfusion parameter maps of the brain; however, its widespread use is limited by the complexity of acquisition protocols and high radiation dose. Previous studies have attempted to reduce radiation exposure by equally lowering the temporal sampling rate; however, it may miss the peak of arterial enhancement, leading to underestimation of blood flow parameter. Here, we investigate the feasibility of using a generative adversarial network (GAN) to generate perfusion maps from 3 phases of CTP (mCTP). The three phases were chosen based on the multiphase computed tomography angiography scanning protocol: the peak arterial input function phase, the peak venous output function phase, and the delayed venous output function phase. The findings demonstrate that the GAN model achieved high visual overlap and performance for cerebral blood flow and time-to-maximum maps, with a mean structural similarity index measure of 0.921 to 0.971 and 0.817 to 0.883, a mean normalized root mean squared error of 0.019 to 0.108 and 0.058 to 0.064, and a mean learned perceptual image patch similarity of 0.039 to 0.088 and 0.141 to 0.146, respectively. For the 2 external datasets, the volume agreement between the model- and CTP-derived infarct and hypoperfusion areas was the intraclass correlation coefficient of 0.731 to 0.883 and 0.499 to 0.635, and the Spearman correlation coefficient of 0.720 to 0.808 and 0.533 to 0.6540, respectively. Qualitative assessments of diagnostic quality further confirmed that the mCTP-derived maps were comparable to those obtained from traditional CTP. In conclusion, the GAN-based model is effective in generating perfusion maps from mCTP, which could serve as a viable alternative to traditional CTP in the diagnostic evaluation of AIS.

The unfolded protein response (UPR) is activated primarily upon alteration of protein folding in the endoplasmic reticulum (ER). This occurs under physiological situations that cause an abrupt increase in protein synthesis, or under redox and metabolic stresses. Among the latter, hyperglycemia and glucose scarcity have been identified as major modulators of UPR signaling. Indeed, the first mammalian UPR effector, the glucose-regulated protein 78, also known as BiP, was identified in response to glucose deprivation. Tunicamycin, arguably the most commonly used drug to induce ER stress responses in vitro and in vivo, is an inhibitor of N-glycosylation. We compile here evidence that the UPR is activated upon physiological and pathological conditions that alter glucose levels and that this is mostly mediated by alterations of protein N-glycosylation, ATP levels, or redox balance. The three branches of the UPR transduced by PERK/ATF4, IRE1/XBP1s, and ATF6, as well as non-canonical ER sensors such as SCAP/SREBP, sense ER protein glycosylation status driven by glucose and other glucose-derived metabolites. The outcomes of UPR activation range from restoring protein N-glycosylation and protein folding flux to stimulating autophagy, organelle recycling, and mitochondrial respiration, and in some cases, cell death. Anabolic responses to glucose levels are also stimulated by glucose through components of the UPR. Therefore, the UPR should be further studied as a potential biomarker and mediator of glucose-associated diseases.

High-precision polarimetry is crucial for sensing and imaging applications, particularly for glucose monitoring within the physiological range of 50 to 400 mg/dl. Traditional approaches often rely on polarisation modulation using magneto-optic or liquid crystal modulators, which require high voltages or currents, limiting their practicality for wearable or implantable devices. In this work, we propose a polarisation-switching technique that alternates between two discrete polarisation states, offering a low-power alternative with miniaturisation potential. Using this method, we achieved a Mean Absolute Relative Difference of 7.7% and a Standard Error of Prediction of 9.6 mg/dl across the physiological glucose range, comparable to commercial continuous glucose monitors. Our approach demonstrates a limit of detection of approximately 40 mg/dl, with measurements performed in phosphate-buffered saline spiked with glucose. This work establishes polarisation switching as a viable alternative for glucose sensing, providing a foundation for future development of wearable and implantable glucose monitoring systems. By eliminating power-intensive components, our approach addresses key limitations of traditional polarimetric methods, paving the way for more accessible and energy-efficient diabetes management technologies.

Coronary atherosclerosis in patients with diabetes mellitus is the most significant pathophysiological mechanism responsible for ischemic heart disease. Atherosclerosis in diabetes is premature, more diffuse, and more progressive, and it affects more coronary blood vessels compared to non-diabetics. Atherosclerosis begins with endothelial dysfunction, continues with the formation of fatty streaks in the intima of coronary arteries, and ends with the appearance of an atherosclerotic plaque that expands centrifugally and remodels the coronary artery. If the atherosclerotic plaque is injured, a thrombus forms at the site of the damage, which can lead to vessel occlusion and potentially fatal consequences. Diabetes mellitus and atherosclerosis are connected through several pathological pathways. Among the most significant factors that lead to atherosclerosis in diabetics are hyperglycemia, insulin resistance, oxidative stress, dyslipidemia, and chronic inflammation. Chronic inflammation is currently considered one of the most important factors in the development of atherosclerosis. However, to date, no adequate anti-inflammatory therapeutic measures have been found to prevent the progression of the atherosclerotic process, and they remain a subject of ongoing research. In this review, we summarize the most significant pathophysiological mechanisms that link atherosclerosis and diabetes mellitus.

Early age at menarche (AAM) is a risk factor for type 2 diabetes later in life, but the pathogenic pathways that confer increased risk remain unknown.

We examined the associations between AAM and inflammatory and glucose metabolism biomarkers among US adult women who were free of diabetes.

Using the National Health and Nutrition Examination Survey (NHANES) 1999-2018, 19 228 women over 20 years old who were free of self-reported cancer and diabetes were included in this cross-sectional analysis. AAM was the self-reported age at first menstruation. C-reactive protein (CRP), fasting glucose, fasting insulin, and ferritin levels were measured as biomarkers of inflammation and glucose metabolism in adult blood samples using latex-enhanced nephelometry, enzymatic, and immunoassay methods. Multiple linear regression was used to relate AAM to the biomarkers.

The median age at the time of blood sample collection was 44 years (interquartile range, 33-62). After age adjustment, there was an association between a lower AAM and higher CRP (P-trend = .006), fasting glucose (P-trend < .0001), fasting insulin (P-trend < .0001), and ferritin (P-trend < .0001). These remained significant after additional adjustment for demographic, reproductive, lifestyle, and adiposity variables, except for ferritin. Smoking modified the effect of AAM on CRP (P-interaction = .014), fasting insulin (P-interaction < .001), and fasting glucose (P-interaction < .001). In stratified analysis, the observed associations became more pronounced in nonsmokers, while they were attenuated to nonsignificance in active smokers.

Earlier age at menarche is associated with an unfavorable inflammatory and glucose metabolic biomarker profile in a nationally representative sample of adult women free of diabetes, especially among nonsmokers.

Cardiovascular, renal, and metabolic diseases are pathophysiologically interdependent, posing a significant global health challenge and being associated with a substantial increase in morbidity and mortality. In 2023, the American Heart Association (AHA) defined this complex network of interconnected health conditions as the cardiovascular-kidney-metabolic (CKM) syndrome. This syndrome is based on common pathophysiological mechanisms, including chronic inflammation, oxidative stress, hyperglycemia and insulin resistance, activation of the renin-angiotensin-aldosterone system (RAAS), and neurohormonal dysfunction, which trigger a vicious cycle where the impairment of one organ contributes to the progressive deterioration of the others. An integrated approach to these conditions, rather than treating them as separate entities, supports a holistic management strategy that helps to reduce the burden on public health and improve patients' quality of life. Existing management focuses on lifestyle modification, glycemic and lipid control, and the use of nephroprotective and cardioprotective therapies. This narrative review aims to synthesize and contextualize existing information on the complex interactions between these systems and on diagnostic approaches, as well as to provide an overview of the available therapeutic options.

Cardiovascular disease (CVD) remains a major global health challenge, particularly affected by glucose metabolism status. However, the relationship between estimated glucose disposal rate (eGDR) and future CVD risk across different glucose metabolism status remains unclear.

We analyzed data from the China Health and Retirement Longitudinal Study (2011-2020) of participants aged ≥ 45 years. The eGDR was calculated using waist circumference, hypertension status, and HbA1c levels. CVD events (stroke or cardiac events) were the outcome. Participants were categorized by glucose metabolism status (normoglycemia, prediabetes, diabetes). Cox proportional hazards models and restricted cubic splines were used to assess associations and potential non-linear relationships.

Among 7,828 participants (52.84% male, mean age 59.01 ± 9.21 years) followed for an average of 8.29 years, 1,944 participants (24.83%) developed CVD. Higher eGDR was inversely associated with CVD risk across all glucose metabolism states. Below the inflection points (11.77, 11.15, and 11.56 mg/kg/min for normoglycemia, prediabetes, and diabetes, respectively), each 1-unit increase in eGDR reduced CVD risk by 14% (HR = 0.86, 95%CI: 0.83-0.89), 10% (HR = 0.90, 95%CI: 0.86-0.93), and 14% (HR = 0.86, 95%CI: 0.81-0.91), respectively.

The eGDR demonstrates a potentially non-linear inverse association with future CVD risk across different glucose metabolism states.

The characteristics of diabetes patients with cardiovascular disease (CVD) in Malaysia are not well understood, especially in terms of metabolic control and treatment profiles. We aimed to determine the characteristics of type 2 diabetes patients with CVD in public primary care clinics in Malaysia. A cross-sectional analysis of the baseline information of an established retrospective cohort dataset was done.

Among 18,312 patients, 4.1% had CVD. In the multiple logistic regression model, CVD was associated with males, older age, longer diabetes duration, hypertension, dyslipidaemia, nephropathy, insulin, antiplatelet agents, and glycosylated haemoglobin A1c control. In contrast, LDL cholesterol control was less common among patients with CVD. The percentage of patients with CVD who achieved the recommended glycosylated haemoglobin A1c ≤ 8%, blood pressure ≤ 135/75 mmHg, and LDL cholesterol < 1.8 mmol/L were 59.5%, 25.3%, and 13.7%, respectively. Meanwhile, 44.7%, 25.6%, and 42.7% of patients without CVD achieved glycosylated haemoglobin A1c ≤ 7.0%, blood pressure ≤ 135/75 mmHg, and LDL cholesterol ≤ 2.6 mmol/L, respectively. Many patients did not achieve the recommended treatment targets. There are ample opportunities to optimise the quality of diabetes management in primary care settings in Malaysia.

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.

Acute lower limb ischemia (ALI) is a life and limb threatening event often affecting patients with type 2 diabetes mellitus (T2DM). Little is known about how T2DM affects the risk of adverse events in patients revascularized for ALI. This study aimed to investigate if there were differences in major outcomes between ALI patients with and without T2DM.

Between 2010 and 2014, 615 patients underwent revascularization for ALI, according to the Swedish Vascular Registry (SWEDVASC). Using the National Diabetes Registry (NDR), 245 (39.8%) of the patients were identified as having T2DM. Uni- and multivariable Cox or logistic regression analyses were performed to evaluate risk differences for major amputation, mortality, major adverse cardiovascular events (MACE), and fasciotomy between patients with and without T2DM.

The rates of major amputation and mortality at one year were 32.7% and 21.6% in the T2DM group, compared to 21.9% and 31.9% in the non-DM group, respectively, resulting in a hazard ratio (HR) of 1.52 (95% confidence interval [CI] 1.12-2.07) for major amputation and HR of 0.64 (95% CI 0.46-0.88) for mortality. At one year, the HR for major amputation was 1.45 (95% CI 0.99-2.11), HR for mortality 0.92 (95% CI 0.61-1.39), HR for combined major amputation/mortality 1.27 (95% CI 0.94-1.72), and HR for MACE 1.24 (95% CI 0.92-1.67) for those with T2DM compared to those without in the multivariable Cox-regression analyses. The multivariable logistic regression analysis showed significantly lower odds of fasciotomy, OR 0.1 (95% CI 0.01-0.51) in the T2DM-group.

T2DM was not significantly associated with higher hazard of major amputation, mortality, combined major amputation/mortality, or MACE after revascularization for ALI, compared to patients without T2DM. Patients with T2DM had significantly lower odds of fasciotomy.