Few studies have investigated the effect of the combined use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) on the cardiovascular (CV) composite outcomes in type 2 diabetes (T2D) patients with acute coronary syndrome (ACS).

We retrospectively collected the data of 1325 T2D patients treated with SGLT2i for more than 3 months before ACS admission at Civil Aviation General Hospital. According to the initiative GLP-1RA use after admission, patients were divided into a combination group (SGLT2i and GLP-1RA) or a SGLT2i group. The primary CV composite outcomes were defined as the first occurrence of major adverse cardiovascular events (MACE) with 1-year, encompassing all cause death, CV death, non-fatal myocardial infarction or stroke, coronary revascularization or heart failure readmission. Propensity score-matched (PSM) was used to control the confounding factors.

After matching, 208 pairs were finally included. Compared with the SGLT2i group, the combination group demonstrated a 31.0 % reduced risk of MACE (HR = 0.690, 95 %CI: 0.488-0.976), attributed primarily to a substantial 22.9 % (HR = 0.771, 95 %CI: 0.599-0.992) reduction in all-cause mortality and a 36.3 % reduction in non-fatal stroke (HR = 0.637, 95 %CI: 0.413-0.982). Subgroup analyses indicated consistent CV benefits across different subgroups (P interaction values >0.05).

The combined use of SGLT2i and GLP-1RA was associated with a significantly decreased risk of MACE primarily driven by the lowering risks of all-cause mortality and nonfatal stroke in T2D patients with ACS, compared with SGLT2i use alone.

Type 2 diabetes mellitus (T2DM) has become a global health concern due to its rapidly increasing prevalence and associated complications. Empagliflozin and dapagliflozin, sodium-glucose co-transporter 2 (SGLT2) inhibitors, have widely used in the management of T2DM. Moreover, empagliflozin and dapagliflozin reduce the risk of cardiovascular events and associated mortality both with and also without diabetes. In the present study, it was investigated empagliflozin and dapagliflozin effects on miRNA expression in nicotinamide/streptozotocin-induced T2DM rats. The male/female rats were divided into four groups: Control, T2DM, T2DM + Empagliflozin, and T2DM + Dapagliflozin. The body weights were monitored weekly and blood pressure measurement were evaluated first and last week. IL-1β, SOD, RAGE, and cTnI levels in serum and heart tissue were detected by ELISA. The RT-PCR was used to analyze the expression levels of miRNAs in the heart tissue of diabetic rats. As a result, the most remarkable findings miR-223, miR-373, miR-22, miR-9, miR-146a, miR-21, miR-144, miR-221, and miR-34a had significantly higher expressions in the control group. Moreover, miR-146a and miR-34a levels are remarkably increased empagliflozin group comparison to the T2DM group. The miR-146a expression was increased dapagliflozin group comparison to the T2DM group. Additionally, treatments with empagliflozin and dapagliflozin showed improvements in histopathological and biochemical examinations.

To examine hospital discharge practices, including clinical and laboratory assessments, in patients with type 2 diabetes mellitus (T2DM) following their first hospitalisation for cardiovascular disease (CVD), and to explore the association of these practices with adverse events, defined as hospital readmission, emergency department visits and mortality.

Retrospective cohort study.

Follow-up for 100 days after a newly diagnosed CVD among patients with T2DM in Region Halland, Sweden.

A total of 1482 patients with T2DM and a new diagnosis of CVD during hospitalisation were included. Patients were followed from hospital discharge for up to 100 days. Inclusion criteria were a hospital discharge diagnosis of CVD and a prior diagnosis of T2DM. Patients with incomplete discharge data or without follow-up records were excluded.

The primary outcome was the overall risk of serious adverse events after hospital discharge, including mortality, hospital readmission and ED encounters, within 100 days of discharge. Secondary outcomes included primary care visits and pharmacotherapy adjustments for CVD and T2DM during the same period.

The readmission rate within the study period was 27%, while 86% of patients visited primary care within 100 days after discharge. Cardiovascular pharmacotherapy increased, with beta-blocker usage rising to 73% and statin use reaching 82%. A significant, though modest, increase in pharmacotherapy for T2DM was observed, with metformin use increasing from 53% to 57% (p<0.001). Laboratory test results and clinical measurements at discharge, including missing glycated haemoglobin values (68%) and elevated systolic blood pressures, were associated with modest treatment adjustments at discharge, suggesting potential gaps in discharge practices and documentation.

Despite moderate improvements in postdischarge pharmacotherapy, limited changes in diabetes management suggest room for optimisation. The findings emphasise the need for improved discharge planning and continuity of care. Future research should investigate the effects of standardised discharge protocols on treatment outcomes and readmission rates for this patient group.

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.

Orforglipron, a novel oral, non-peptide glucagon like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving body weight reduction and glycemic control. However, its potential benefits in improving cardiovascular (CV) risk factors have yet to be determined. We assessed the effect of orforglipron in participants with type 2 diabetes (T2D) and/or overweight or obesity on blood pressure, lipid, and inflammatory biomarkers associated with risk for major adverse cardiovascular events.

Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers. For the T2D study, participants mean age 59 years, 40% were assigned female at birth with a mean HbA1c of 8.1% and mean BMI of 35.3 kg/m2; they received once daily orforglipron doses (3, 12, 24, 36, or 45 mg) or once weekly subcutaneous dulaglutide 1.5 mg, or placebo. In the obesity study, participants had a mean age 54 years, 60% were assigned female at birth, and mean BMI was 37.9 kg/m2; they received once daily orforglipron (12, 24, 36, or 45 mg) or placebo. The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure, lipids (cholesterol, triglycerides, Apolipoprotein B (ApoB), Apolipoprotein C3 (ApoC3), N-terminal pro-b-type natriuretic peptide (NT-pro-BNP), and inflammatory biomarkers (high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6)) were assessed.

Significant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity. In both studies, improvements in blood pressure, lipid parameters, and most of the evaluated biomarkers were of similar magnitude after treatment with 12 mg orforglipron as with 24, 36, and 45 mg.

Orforglipron treatment was associated with beneficial changes in CV risk markers in participants with T2D and in participants with overweight/obesity without T2D. (Clinicaltrials.gov: NCT05048719, NCT05051579).

Diabetes mellitus remains a prevalent condition worldwide and a significant risk factor for atherosclerotic cardiovascular disease. Recent evidence suggests the use of glucose-lowering therapies with cardiovascular benefit in optimising the cardiometabolic profile of patients with type 2 diabetes mellitus. However, uptake remains low. This study was carried out to assess the impact of a novel cardiodiabetes service for the management of patients with diabetes mellitus presenting with acute coronary syndromes.

A retrospective, observational, registry-based analysis was performed among patients presenting with an acute coronary syndrome and diabetes mellitus to a regional heart centre before and after the implementation of a cardiodiabetes service. Intergroup comparison was made for the proportion of patients having a valid glycated haemoglobin during admission, initiation of guideline-recommended glucose and lipid-lowering therapies.

At median follow-up of 29.7 months, a valid HbA1c measurement at baseline was lower in the pre-intervention compared to the post-intervention group (556/711 [78.2%] vs. 302/362 [83.4%], p = 0.043) while more patients in the post-intervention group were prescribed sodium-glucose co-transporter inhibitors (297/362 [82.0%] vs. 359/711 [50.5%]). All-cause mortality (5.2 vs. 12.3 [events/100 patient-years], relative ratio [RR] 0.42, 95% confidence interval [CI] 0.28-0.61, and p < 0.001), first events of acute kidney injury (AKI) (10.0 vs. 13.0, RR 0.77, CI 0.57-1.03, p = 0.090) and all events of AKI (16.6 vs. 22.1, RR 0.75, CI 0.60-0.94, p = 0.015) were significantly lower in the post-intervention group.

The introduction of a joint-speciality cardiodiabetes service improved the care and survival of patients with acute coronary syndrome and diabetes mellitus.

To evaluate the impact of statin therapy on warfarin dose requirements in diabetic patients and to assess the performance of various machine learning algorithms in predicting optimal warfarin dosing.

The datasets available for total participants of 628 (216 diabetics and 412 non-diabetic patients) were analyzed. We categorized the patients according to height, weight, gender, race, and age, plasma international normalized ratio (INR) on reported therapeutic dose of warfarin, target INR, warfarin dose, statin therapy, and indications for warfarin. Various models were tested on data of patients from the International Warfarin Pharmacogenetics Consortium (IWPC). Data preprocessing involves structuring and handling missing values. Six predictive models, including least absolute shrinkage and selection operator (LASSO), k-nearest neighbors (KNN), support vector regression (SVR), linear regression (LR), decision tree, and random forest (RF), were employed in predicting optimal warfarin dosage. The best dose for each patient will be predicted using one of the six regression models.

This comparative study showed that the mean (and the standard deviation) of warfarin dose for diabetic and non-diabetic patients were 38.73 (15.37) and 34.50 (18.27) mg per week, respectively. Furthermore, the impact of various statin they use is considered and patient undergoing atorvastatin and rosuvastatin therapy against the necessity of high dose warfarin if the diabetic patients use lovastatin and fluvastatin.

Diabetic patients under statin therapy, considering the specific statin used, require different warfarin dose. Through the application of advanced machine learning, models as dosing predictors may attenuate the adverse effects of warfarin.

Acetylcholine (ACh) secreted by the non-neuronal cholinergic system (NNCS), an intrinsic system found in the mammalian heart, is not dependent on neuronal inputs for its synthesis. Accumulating evidence demonstrates that ACh exerts multifaceted cardioprotective effects through the NNCS. Under extreme stress or demand, ACh slows heart rate by modulating cardiac chronotropy. Simultaneously, it protects the myocardium from ischemic, hypoxic, and other stressors. Beyond its direct effects on the heart, ACh has also been found to play a vital role in controlling mitochondrial homeostasis via specific signaling pathways in hearts. Through these pathways, ACh induces mitochondrial biogenesis and the renewal of the mitochondrial network while suppressing the generation of reactive oxygen species (ROS) within the mitochondria. Aging weakens the cardiac NNCS, lowering the heart's local ACh availability. Reducing mitochondrial activity and ROS-related inflammatory stress are essential indicators of cardiac aging and related disorders. As individuals age, mitochondria become less efficient at generating sufficient ATP to sustain the heart's ability to pump oxygen-rich blood and reduce cardiac performance. Therefore, the exciting prospect of increasing ACh secretion or stabilizing ACh levels through therapeutic targeting of the NNCS may provide a beacon of hope in the fight against age-related cardiovascular disorders. Further elucidating the mechanisms by which the NNCS regulates cardiac function through mitochondria may develop a novel treatment that rejuvenates the properties of this evolutionarily conserved system of the heart.

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.

Previous observational studies on the association between the consumption of fruit juice and the risk of type 2 diabetes mellitus have reported inconsistent findings. We investigated the association using a meta-analysis of prospective cohort studies.

Studies were identified through PubMed and EMBASE searches from inception to August 3, 2024. We calculated pooled relative risks (RRs) and 95% confidence intervals (CIs). The consumption of fruit juice was categorized into 100% fruit juice and non-100% fruit juice. The primary outcome was the incidence of type 2 diabetes mellitus.

Out of 1591 articles, 14 prospective cohort studies were included in the final analysis. In the meta-analysis of all studies, there was no significant association between the consumption of overall fruit juice and the risk of type 2 diabetes mellitus (RR, 1.06 [95% CI, 0.98-1.15], P = 0.170). In the subgroup meta-analysis by juice type, non-100% fruit juice was statistically significantly associated with an increased risk of type 2 diabetes mellitus (RR, 1.15 [95% CI, 1.03-1.28], P = 0.012), while there was no significant association between the consumption of 100% fruit juice and the risk of type 2 diabetes mellitus. An increased risk of type 2 diabetes mellitus by fruit juice was observed only in Asian populations (RR, 1.17 [95% CI 1.02-1.34], P = 0.023).

The consumption of non-100% fruit juice increased the risk of type 2 diabetes mellitus. Unlike whole fruit consumption, 100% fruit juice had no beneficial effect on the risk of type 2 diabetes mellitus.

Cardiovascular disease complications are the leading cause of morbidity and mortality in patients with Type 2 diabetes (T2DM). Left ventricular diastolic dysfunction (LVDD) is one of the earliest myocardial characteristics of diabetic cardiac dysfunction. Therefore, we aimed to develop an LVDD-risk predictive model to diagnose cardiac dysfunction before severe cardiovascular complications arise. We trained an artificial neural network model to predict LVDD risk with patients' clinical information. The model showed better performance than classical machine learning methods such as logistic regression, random forest and support vector machine. We further explored LVDD-risk/protective features with interpretability methods in neural network. Finally, we provided a freely accessible web server called LVDD-risk, where users can submit their clinical information to obtain their LVDD-risk probability and the most noteworthy risk indicators.

To evaluate the effects of vagus nerve stimulation (VNS) on selected health-related outcomes in MetS.

Seventy men with metabolic syndrome (MetS) aged between 45 and 55, with a body mass index (BMI) ranging from 30 to 35 kg/m2, were randomly divided into study group that received a vagus nerve stimulation (VNS) and circuit weight training (CWT) and control group which underwent a CWT. An Emotional Eating Scale (EES) and a Short Assessment of Patient Satisfaction (SAPS) were used to evaluate emotional eating and patient satisfaction with their therapy, respectively. Salivary cortisol levels were measured between 8 and 9 am, and body weight was detected after 8 h of fasting. The clinical trial ID was NCT05785117.

There was a significant change in EES and SAPS scale scores in both groups post-intervention; however, the study group showed higher scores than the control group. Furthermore, the change percentage of weight and salivary cortisol in the study group was 8.9% and 44.5%, respectively, which were higher than in the control group (2.9% and 40.6%, respectively).

VNS and CWT were considered promising, simple, and cost-effective interventions for improving emotional eating, patient satisfaction, salivary cortisol, and body weight in individuals with MetS.

Type 2 diabetes is a significant risk factor for cardiovascular disease, particularly coronary heart disease, heart failure, and diabetic cardiomyopathy. Diabetic cardiomyopathy, characterized by heart dysfunction in the absence of coronary artery disease or hypertension, is triggered by various mechanisms, including hyperinsulinemia, insulin resistance, and inflammation. At the cellular level, increased insulin resistance leads to an imbalance in lipid and glucose metabolism, causing oxidative stress, mitochondrial dysfunction, and excess production of reactive oxygen species (ROS). This disrupts normal heart function, leading to fibrosis, hypertrophy, and cardiac remodeling. In diabetic patients, the excessive accumulation of fatty acids, advanced glycation end products (AGEs), and other metabolic disturbances further contribute to endothelial dysfunction and inflammatory responses. This inflammatory environment promotes structural damage, apoptosis, and calcium-handling abnormalities, resulting in heart failure. Additionally, diabetes increases the risk of arrhythmias, such as atrial fibrillation, which worsens cardiac outcomes. New insights into these molecular mechanisms have led to improvements in diabetes management, focusing on mitigating complications and understanding the cellular processes involved. Recent therapeutic advances, such as SGLT-2 inhibitors, have shown promise in addressing the energy imbalance and cardiac dysfunction seen in diabetic cardiomyopathy, offering new hope for better cardiovascular outcomes.

The relationship between serum bilirubin levels and type 2 diabetes mellitus (T2DM) in individuals with schizophrenia (SCZ) remains poorly understood. This study investigated associations between total, conjugated, and unconjugated bilirubin (TB, CB, and UCB) and T2DM risk, while exploring the potential role of inflammatory pathways.

The study included 862 SCZ patients from Baiyun Jingkang Hospital, Guangzhou, the People's Republic of China. Cox proportional hazards model assessed baseline bilirubin and T2DM risk, while causal mediation analysis explored inflammatory markers. Latent class trajectory model and logistic regression model evaluated the association between multi-timepoint trajectories of bilirubin and T2DM prevalence.

Over a median 3.19-year follow-up, 63 T2DM cases were diagnosed. Adjusted hazard ratios per 1 μmol/L increase were 0.88 (95 % CI: 0.82-0.95) for TB, 0.71 (0.57-0.89) for CB, and 0.86 (0.78-0.95) for UCB. Compared to the lowest tertile, the highest tertiles of TB, CB, and UCB were associated with 63 %, 74 %, and 63 % reduced T2DM risks, respectively. Lymphocyte count mediated TB (8.77 %), CB (11.68 %), and UCB (8.34 %); CRP mediated TB (3.33 %) and UCB (4.60 %) with T2DM. Persistently high TB and UCB levels were associated with lower T2DM prevalence (OR = 0.22 and 0.30, respectively).

Elevated bilirubin levels are associated with reduced T2DM risk in SCZ patients, with lymphocyte count and CRP partially mediating the bilirubin-T2DM relationship. And persistently high levels of TB and UCB linked to a lower prevalence of T2DM. These findings suggest that moderately elevated serum bilirubin may reduce T2DM risk among SCZ patients.

The limited evidence reports the relationship between plasma dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) and Diabetic kidney disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM). Therefore, the present study aimed to evaluate the diagnostic potential of dp-ucMGP in DKD among T2DM patients.

This cross-sectional study was conducted from December 2023 to January 2025, including 75 T2DM patients. Participants were classified into three groups based on urinary albumin-to-creatinine ratio (UACR): Normoalbuminuria, microalbuminuria, and macroalbuminuria with n = 25 in each group. Pearson correlation analysis was performed to assess the relationship between dp-ucMGP and other biochemical parameters. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the diagnostic potential of dp-ucMGP for early detection of DKD. A p value < 0.05 was considered statistically significant.

The plasma dp-ucMGP levels were significantly higher in T2DM patients in the macroalbuminuria group, with a mean of 1069.86 ± 417.56 pmol/L, followed by the microalbuminuria (842.72 ± 342.02 pmol/L) and normoalbuminuria (586.38 ± 336.15 pmol/L) groups. Similarly, higher dp-ucMGP levels were observed in patients with DKD severity stage IV (1401.53 ± 401.49 pmol/L). A negative correlation with eGFR (r = -0.807, p < 0.0001) and a positive correlation with age, serum creatinine, UACR, blood urea, uric acid and triglycerides were observed. The area under the curve (AUC) was 0.913 (95% CI: 0.820-0.960; p < 0.0001) for dp-ucMGP.

In conclusion, our findings revealed that plasma dp-ucMGP could be a potential biomarker to predict the early detection of DKD in patients with T2DM.

Among noncommunicable diseases, cardiovascular disease (CVD) is the leading cause of mortality and morbidity. In China, diabetes is renowned for its high incidence rate, and the body roundness index (BRI) is an emerging indicator for assessing obesity, particularly abdominal obesity. High BRI may lead to new-onset CVD events. However, the relationships between the BRI and new-onset CVD in individuals with or without diabetes remain unclear.

Data for this analysis were extracted from the China Health and Retirement Longitudinal Study (CHARLS). Our research utilized a cohort that was meticulously assessed over a period from 2011 to 2018, encompassing a comprehensive follow-up of 17,708 participants. Ultimately, this study focused on a subset of 6,737 individuals aged 45 years or older. Methodological approaches include Cox regression, Kaplan-Meier survival analysis, restricted cubic splines (RCS) analysis, receiver operating characteristic (ROC) curve analysis, subgroup analysis, and mediation analysis to explore the relationships of interest.

This study included 6,737 participants, all of whom were above the age of 45. Our findings revealed that within this demographic group, 1,481 (22.0%) patients experienced new-onset CVD. The Kaplan-Meier survival analysis further revealed that the group characterized by non-diabetes mellitus (Non-DM) had the lowest cumulative incidence of CVD compared with the diabetes mellitus (DM) group. Multivariate Cox regression revealed that in the fully adjusted model (Model 3) (HR = 1.122, 95% CI = 1.080 to 1.167), BRI was associated with the risk of CVD in the Non-DM group during the three-wave follow-up. RCS analysis revealed a positive, linear-like dose‒dependent relationship between BRI and new-onset CVD in Non-DM patients (P = 0.007, P for nonlinearity = 0.938). Smoking could affect the ability of the BRI to predict the incidence rate of CVD in the total population and in the population without diabetes (P interaction = 0.007). Moreover, the mediating effect of the BRI on new-onset CVD among diabetic patients was particularly pronounced in the long term, exceeding 4 years.

Our findings demonstrate a significant association between the BRI and CVD risk in non-diabetic individuals, with diabetes influencing the incidence and risk of new-onset CVD in middle-aged and elderly Chinese populations through the BRI playing a mediating role. As an obesity indicator, the BRI provides a valuable tool for early detection and intervention of CVD.

Not applicable.

There is limited evidence regarding whether obesity modifies the association between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and the risk of cardiovascular events. We assessed whether baseline body mass index (BMI) modifies the association between SGLT2i use and the risk of major adverse cardiovascular events (MACE) and heart failure (HF) in patients with type 2 diabetes (T2D).

We used the nationwide claims data of Korea (September 2014-December 2022) to construct an active-comparator, new-user cohort of patients with T2D stratified by the Asian BMI categories: normal weight, 18.5-23 kg/m2; overweight, 23-25 kg/m2; and obesity, ≥25 kg/m2. New-users of SGLT2i were propensity score (PS)-matched with new-users of dipeptidyl peptidase 4 inhibitor (DPP4i) in a 1:1 ratio. The co-primary outcomes were 4-point MACE and hospitalization for HF (HHF). Patients were followed up using an as-treated exposure definition. PS-matched hazard ratios (HR) with 95% confidence intervals (CI) were estimated using the Cox model.

New-users of SGLT2i and DPP4i were PS-matched in a 1:1 ratio (n = 231 332 pairs; normal weight, 21 285 pairs; overweight, 35 372 pairs; and obesity, 174 675 pairs). The overall HR for the risk of MACE with SGLT2i versus DPP4i use was 0.90 (95% CI: 0.86-0.95), with no evidence of effect modification by baseline BMI (p for homogeneity = 0.27). The risk of HHF decreased in the overall cohort (HR: 0.53, 95% CI: 0.44-0.64), as well as in the obesity (HR: 0.47, 95% CI: 0.37-0.58) and overweight (HR: 0.49, 95% CI: 0.31-0.78) groups but not in the normal-weight (HR: 0.88, 95% CI: 0.59-1.31) group, with evidence of effect modification by the BMI (p for homogeneity = 0.01).

The association between SGLT2i use and the risk of MACE and HHF was significant in patients with obesity. Baseline BMI was an effect modifier in the association between SGLT2i use and the risk of HHF, with a more pronounced association observed with increasing BMI and with no significant effect modification of the association noted in patients with normal weight.

This study aimed to evaluate the effects of Adaptive Postural Balance Cardiac Rehabilitation Exercise (APBCRE) on glycolipid metabolism and exercise endurance in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Specifically, we compared the efficacy of APBCRE with aerobic exercise (AE) alone and irregular exercise (IE).

This randomized controlled trial included 348 patients with CAD, comprising 261 patients with T2DM and 87 non-diabetic CAD patients as a control group. Participants were randomly assigned to one of four groups: the APBCRE group, the AE group, the IE group, or the non-diabetic AE control group. The intervention lasted 8 weeks, including a structured 6-week training phase. Metabolic markers and exercise endurance were assessed at baseline (week 1) and post-intervention (week 8). Cardiopulmonary exercise testing (CPET) was utilized to individualize exercise prescriptions and optimize intervention intensity.

The APBCRE group demonstrated significant improvements in fasting blood glucose (FBG) (-11.34%, from 7.89 to 6.99 mmol/L, p < 0.05), HbA1c (-8.87%, from 7.20% to 6.56%, p < 0.05), and LDL-C levels (-12.21%, from 2.44 to 2.14 mmol/L, p < 0.05) compared to the AE and IE groups. While both APBCRE and AE improved lipid profiles, APBCRE demonstrated superior enhancements in exercise endurance, with ˙VO 2 max increasing by 18.71% (from 14.19 to 16.86 mL/min/kg, p < 0.05) and AT ˙VO 2 increasing by 16.00% (from 11.62 to 13.48 mL/min/kg, p < 0.05).

These findings support the efficacy of APBCRE in improving glycolipid metabolism, exercise endurance, and neuromuscular coordination in patients with CAD and T2DM compared to AE alone.

The role of inflammation in shaping death risk in diabetes is still unclear.

To study whether inflammation is associated with and helps predict mortality risk in patients with type 2 diabetes. To explore the intertwined link between inflammation and tryptophan metabolism on death risk.

There were 2 prospective cohorts: the aggregate Gargano Mortality Study (1731 individuals; 872 all-cause deaths) as the discovery sample, and the Foggia Mortality Study (490 individuals; 256 deaths) as validation sample. Twenty-seven inflammatory markers were measured. Causal mediation analysis and in vitro studies were carried out to explore the link between inflammatory markers and the kynurenine to tryptophan ratio (KTR) in shaping mortality risk.

Using multivariable stepwise Cox regression analysis, interleukin (IL)-4, IL-6, IL-8, IL-13, RANTES, and interferon gamma-induced protein-10 (IP-10) were independently associated with death. An inflammation score (I score) comprising these 6 molecules is strongly associated with death in both the discovery and the validation cohorts HR (95% CI) 2.13 (1.91-2.37) and 2.20 (1.79-2.72), respectively. The I score improved discrimination and reclassification measures (all P < .01) of 2 mortality prediction models based on clinical variables. The causal mediation analysis showed that 28% of the KTR effect on mortality was mediated by IP-10. Studies in cultured endothelial cells showed that 5-methoxy-tryptophan, an anti-inflammatory metabolite derived from tryptophan, reduces the expression of IP-10, thus providing a functional basis for the observed causal mediation.

Adding the I score to clinical prediction models may help identify individuals who are at greater risk of death. Deeply addressing the intertwined relationship between low-grade inflammation and imbalanced tryptophan metabolism in shaping mortality risk may help discover new therapies targeting patients characterized by these abnormalities.

Metabolic syndrome (MetS) is a global health concern, characterized by a combination of dyslipidemia, insulin resistance, obesity, and hypertension, significantly increasing the risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Gut microbiota plays a pivotal role in MetS pathophysiology, with dysbiosis exacerbating metabolic impairments. Delites™, a supplement inspired by Traditional Chinese Medicine, has shown potential in modulating gut microbiota and mitigating MetS.

This study aimed to evaluate the effects of Delites™ supplementation on metabolic health and gut microbiota composition in male Sprague Dawley rats fed a cholesterol- and fat-enriched diet (CFED).

A randomized preclinical trial was conducted on 32 rats divided into four groups: control-normal, CFED, CFED+low-dose Delites™ (54 mg/kg), and CFED+high-dose Delites™ (108 mg/kg). Parameters including lipid profiles, enzymatic activity, molecular biomarkers, and gut microbiota composition were analyzed.

Delites™ significantly improved lipid profiles, reduced inflammation (TNF-α), enhanced anti-inflammatory markers (IL-10), and increased energy metabolism regulator PGC-1α. Gut microbiota modulation showed increased beneficial genera (Bifidobacterium, Lactobacillus) and reduced pathogenic Proteus, improving microbial diversity.

Delites™ supplementation effectively mitigates MetS through metabolic and microbiota modulation. These findings highlight its potential for precision medicine approaches to combat metabolic disorders. Further research is needed to explore its long-term effects and translational relevance in humans.

Background/Objectives: Cardiovascular complications are the most common cause of mortality and morbidity in diabetic patients. Therefore, the aim of antidiabetic therapy should not only be to provide glucose regulation but also to protect patients from complications and related mortality. Brain natriuretic peptide (BNP) is a peptide secreted as a result of myocardial stress. BNP levels increase under conditions of increased myocardial stress, such as heart failure. It is an important marker not only at the time of diagnosis but also during follow-up. In our study, we aimed to evaluate BNP levels and thus, the factors affecting the risk of developing heart failure during the course of diabetes. Methods: This study was conducted at the diabetes outpatient clinic of the University of Health Sciences, Haseki Training and Research Hospital. A total of 252 patients met the inclusion criteria and were enrolled in the study. All study participants were patients with a confirmed diagnosis of type 2 diabetes. Laboratory parameters, including BNP values, comorbidities, and anamnesis data, were recorded. Results: The mean BNP levels were significantly lower in patients using metformin and pioglitazone. Other antidiabetic medications were not associated with BNP levels. BNP levels were positively correlated with age and diabetes duration and negatively correlated with hemoglobin levels. According to regression analysis, age, metformin use, and hemoglobin levels were found to independently affect BNP levels. Conclusions: Our findings suggest that metformin could potentially play a significant role in preventing the development of heart failure in diabetic patients currently not experiencing this complication owing to its favorable effects on myocardial stress. This suggests metformin's potential in preventing heart failure in type 2 diabetic patients.

Coronary heart disease (CHD) is a prevalent type 2 diabetes mellitus (T2DM) complication. Further, the risk stratification before angiography may help diagnose T2DM with CHD early. However, few studies have investigated the coronary imaging characteristics and risk factors of patients with T2DM complicated with CHD.

To compare the differences in coronary imaging between patients with T2DM with and without CHD, determine the risk factors of T2DM complicated with CHD, and establish a predictive tool for diagnosing CHD in T2DM.

This study retrospectively analyzed 103 patients with T2DM from January 2022 to May 2024. They are categorized based on CHD occurrence into: (1) The control group, consisting of patients with T2DM without CHD; and (2) The observation group, which includes patients with T2MD with CHD. Age, sex, smoking and drinking history, CHD family history, metformin (MET) treatment pre-admission, body mass index, fasting blood glucose (FBG), triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase, aspartate aminotransferase, glycosylated hemoglobin (HbA1c), and coronary imaging data of both groups were collected from the medical record system. Logistic risk analysis was conducted to screen risk factors. The prediction model's prediction efficiency was evaluated with receiver operating characteristic curves.

The control and observation groups consisted of 48 and 55 cases, respectively. The two groups were statistically different in terms of age (t = 2.006, P = 0.048), FBG (t = 6.038, P = 0.000), TG (t = 2.015, P = 0.047), LDL-C (t = 2.017, P = 0.046), and BUN (t = 2.035, P = 0.044). The observation group demonstrated lower proportions of patients receiving MET (χ 2 = 5.073, P = 0.024) and higher proportions of patients with HbA1c of > 7.0% (χ 2 = 6.980, P = 0.008) than the control group. The observation group consisted of 15, 17, and 23 cases of moderate stenosis, severe stenosis, and occlusion, respectively, with a greater number of coronary artery occlusion cases than the control group (χ 2 = 6.399, P = 0.041). The observation group consisted significantly higher number of diffuse lesion cases at 35 compared with the control group (χ 2 = 15.420, P = 0.000). The observation group demonstrated a higher right coronary artery (RCA) stenosis index (t = 6.730, P = 0.000), circumflex coronary artery (LCX) stenosis index (t = 5.738, P = 0.000), and total stenosis index (t = 7.049, P = 0.000) than the control group. FBG [odds ratio (OR) = 1.472; 95% confidence interval (CI): 1.234-1.755; P = 0.000] and HbA1c (OR = 3.197; 95%CI: 1.149-8.896; P = 0.026) were independent risk factors for T2DM complicated with CHD, whereas MET (OR = 0.350; 95%CI: 0.129-0.952; P = 0.040) was considered a protective factor for CHD in T2DM.

Coronary artery occlusion is a prevalent complication in patients with T2DM. Patients with T2MD with CHD demonstrated a higher degree of RCA and LCX stenosis than those with T2DM without CHD. FBG, HbA1c, and MET treatment history are risk factors for T2DM complicated with CHD.

The purpose of this study is to investigate the relationship between the weight-adjusted waist index (WWI) and the incidence of carotid atherosclerotic plaque in patients with type 2 diabetes (T2DM) in the Chinese population.

A retrospective cross sectional analysis was conducted on data from 801 adult patients from May 2018 to January 2024. Spearman's correlation analysis was used to determine the correlation between WWI and carotid atherosclerotic plaque and analyzed the factors influencing carotid atherosclerotic plaque through binary logistic regression. Additionally, the area under the receiver operating characteristic (ROC) curve (AUC) was calculated to analyze the optimal cut-off point for WWI to predict carotid atherosclerotic plaque.

Compared with the non-carotid atherosclerotic plaque group, the incidence of hypertension, systolic blood pressure, in the carotid atherosclerotic plaque group were higher than in the non-carotid plaque group(P < 0.05). Correlation analysis showed that WWI was positively correlated with carotid atherosclerotic plaque (r = 0.263)(P < 0.05). Binary logistic regression analysis showed that WWI was an independent risk factor for carotid atherosclerotic plaque in patients with T2DM. The ROC curve analysis for the WWI yielded an AUC of 0.65 (95% CI = 0.611-0.69, P < 0.05) for predicting the presence of carotid atherosclerotic plaque.

WWI was independently associated with the occurrence of carotid atherosclerotic plaque in patients with T2DM. Given its simplicity and widespread use, WWI emerges as a novel and practical predictor for assessing the risk of developing carotid atherosclerotic plaque in Chinese patients with T2DM.

To address challenges such as limited loading capacity, restricted targeting precision, and low yield of natural exosomes as drug carriers, the fusion of liposomes and exosomes to create hybrid vesicles has emerged as a viable solution approach. While current research mainly focuses on designing functionalized liposomes, less attention is given to how liposome membrane materials affect the elasticity of these hybrids and their delivery efficiency. This study utilized milk exosomes (mExos) as model exosomes, and generated hybrid vesicles with varying elasticity through the fusion of phospholipids with differing chain lengths, examining the disparities among various hybrid vesicles in their ability to overcoming the gastrointestinal barriers. It was observed that while hard hybrid vesicles exhibited reduced mucus penetration compared to soft hybrid vesicles, they demonstrated a notably higher efficacy in traversing the epithelial cell barrier. The enhanced transepithelial cell capability of hard vesicles can be attributed to their reduced tendency to aggregate in the lysosome through the down-regulated clathrin-mediated endocytosis pathway, as well as by the strengthening of the endoplasmic reticulum-Golgi exocytosis pathway due to their rigid characteristics. In comparison to soft hybrid vesicles, semaglutide (SET) loaded hard hybrid vesicles demonstrated improved in vivo epithelial permeability, enhanced oral bioavailability, and better therapeutic effectiveness. This study could provide valuable insights for determining the optimal elasticity of exosome-liposome hybrid vesicles in the development of oral nanocarriers.

Diabetic cardiomyopathy is a notable microvascular complication of diabetes, characterized primarily by myocardial fibrosis and functional abnormalities. Long-term hyperglycemia induces excessive activation and recruitment of immune cells and triggers the cascade of inflammatory responses, resulting in systemic and local cardiac inflammation. Emerging evidence highlights the significant roles of immunology in modulating the pathology of diabetic cardiomyopathy. As the primary effectors of inflammatory reactions, immune cells are consistently present in cardiac tissue and can be recruited under pathological hyperglycemia circumstances. A disproportionate favor to proinflammatory types of immune cells and the increased proinflammatory cytokine levels mediate fibroblast proliferation, phenotypic transformation, and collagen synthesis and ultimately rise to cardiac fibrosis and hypertrophy. Meanwhile, the severity of cardiac fibrosis is also strongly associated with the diverse phenotypes and phenotypic alterations of the immune cells, including macrophages, dendritic cells, mast cells, neutrophils, and natural killer cells in innate immunity and CD4+ T lymphocytes, CD8+ T lymphocytes, and B lymphocytes in adaptive immunity. In this review, we synthesized the current analysis of the critical role played by the immune system and its components in the progression of diabetic cardiomyopathy. Finally, we highlight preclinical and clinical immune targeting strategies and translational implications.

Cardiovascular (CV) disease (CVD) risk is greater in patients with diabetes mellitus and is the major contributor to disability and premature mortality compared to those who do not have diabetes. The clinical implications of CVD in people with type 2 diabetes mellitus (T2DM) have increased the emphasis on concurrent treatment to prevent the onset of CVD through personalized management for glycemic control and CVD risk management.

Key opinion leaders, comprising 98 cardiologists from across India, participated in seven advisory board meetings held in various cities to explore the challenges and strategies for the early initiation of fixed-dose combinations (FDCs) of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) with a focus on the combination of dapagliflozin and sitagliptin in addressing the CVD risks in patients with T2DM and high risk for CV complications. The expert group discussed the available literature evidence from the clinical trials, systematic reviews, and real-world studies on the benefits of FDC of SGLT2i and DPP4i and FDC of dapagliflozin and sitagliptin to provide rational and practical guidance for its optimal use in addressing the CVD risks in patients with T2DM.

The expert group emphasized the importance of timely glycemic control and early initiation of combination therapy of FDC of SGLT2i + DPP4i in T2DM with CVD risks. Addressing multiple pathophysiological aspects of T2DM is crucial, and considering combination therapy with SGLT2i and DPP4i may be pertinent in this context. Combining dapagliflozin and sitagliptin in FDC to target multiple pathophysiological pathways for T2DM appears to have several glycemic and extra-glycemic benefits.

This practical guidance document provides valuable insights from leading cardiologists that would support clinicians in selecting the synergistic combination SGLT2i + DPP4i (dapagliflozin + sitagliptin) FDC as an appropriate treatment choice in early intensive therapy in managing people with T2DM and CVD risk for better patient outcomes. The expert opinion in this guidance builds on the established guideline recommendations on FDC of SGLT2i and DPP4i.

Semaglutide has demonstrated efficacy in both glycemic control and weight loss. This systematic review and meta-analysis aimed to assess the efficacy and safety of the combined use of semaglutide and basal insulin in individuals diagnosed with type 2 diabetes mellitus (T2DM).

PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to identify relevant publications. The primary outcome measure was the change in HbA1c levels. Secondary outcome measures encompassed change in body weight, fluctuations in FPG levels, occurrence of adverse events, serious adverse events, hypoglycemic episodes, and gastrointestinal reactions including nausea, vomiting, and diarrhea. Mean differences (MDs) and relative risk (RR) with confidence intervals (CI) of 95 % were used to analyze the deference.

7 RCTs with 2354 patients were incorporated into the study. Compared to placebo or other active treatment, the addition of semaglutide to basal insulin demonstrated significant reductions in hemoglobin A1c (HbA1c) [mean differences (MD): -1.17 %, P < 0.00001], body weight [MD -5.99 kg, P < 0.00001], and fasting blood glucose (FPG) [MD -1.08 %, P < 0.00001]. No evidence indicated a higher risk of adverse events [RR 1.46, P = 0.13]. However, it did result in increased rates of gastrointestinal adverse events, including nausea, vomiting and diarrhea.

The combination treatment of semaglutide and basal insulin demonstrates significant improvements in glycemic control and reduction in body weight, without an increased risk of hypoglycemia. Our findings provided support for the utilization of a combination therapy involving semaglutide and basal insulin in T2DM.

Impaired cardiac microvascular function is a significant contributor to diabetic cardiomyopathy. Rnd3 expression is notably downregulated in cardiac microvascular endothelial cells under diabetic conditions. Rnd3 overexpression mitigates diabetic myocardial microvascular injury and improves cardiac function through the Rock1/myosin light chain signaling pathway. Rnd3 facilitates the recruitment and interaction with Trim40 to promote Rock1 ubiquitination, thereby preserving endothelial barrier integrity in the diabetic heart.

Patients with type 2 diabetes mellitus (T2DM) predominantly experience mortality due to cardiovascular diseases (CVD), particularly in low- and middle-income nations. Among these, heart failure (HF) is the most severe cardiovascular complication in terms of prognosis and management. Despite advancements in individualized glycemic control and cardiovascular risk management, including the development of novel glucose- and lipid-lowering agents, the prevalence of HF in T2DM patients remains persistently high. This indicates that factors beyond hyperglycemia significantly contribute to the heightened risk of HF associated with T2DM. This review examines critical factors influencing CVD risk in T2DM, particularly the roles of reduced heart rate variability (HRV), a marker of autonomic dysfunction, and chronic inflammation, both of which play pivotal roles in HF pathogenesis. Recent evidence highlights the potential of vagus nerve activation to modulate these risk factors, underscoring its capacity to reduce T2DM-related cardiovascular complications. Specifically, we discuss the therapeutic promise of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive intervention to enhance vagal tone, decrease systemic inflammation, and improve cardiovascular outcomes in T2DM. By addressing the interplay among HRV, microvascular disease, and inflammation, this review provides a comprehensive perspective on the potential utility of taVNS in managing HF in T2DM.

Background and Objectives: Type 2 diabetes (T2D) and prediabetes represent major global health concerns, with obesity being a key risk factor. However, recent evidence suggests that the adipose tissue composition and distribution play a more critical role in metabolic dysfunction than the total body weight or body mass index (BMI). This study evaluates the predictive capacity of the Córdoba Equation for Estimating Body Fat (ECORE-BF) for identifying individuals at high risk of developing T2D and prediabetes. Materials and Methods: A cross-sectional study was carried out involving 418,343 Spanish workers. Body fat percentage was estimated using the ECORE-BF equation, and diabetes risk was assessed using validated predictive models, including the Finnish Diabetes Risk Score (FINDRISC), QDiabetes score (QD-score), and others. The discriminatory power of ECORE-BF in predicting T2D and prediabetes was assessed using receiver operating characteristic (ROC) curve analysis. Results: ECORE-BF showed a strong correlation with high-risk classifications across all diabetes risk scales. The area under the ROC curve (AUC) exceeded 0.95 for both men and women, demonstrating high predictive accuracy. Conclusions: Adipose tissue distribution, particularly visceral adiposity, is a central factor in metabolic dysfunction. ECORE-BF provides a cost-effective alternative for large-scale T2D and prediabetes risk assessment. Future research should explore the impact of visceral adipose tissue reduction on diabetes prevention and the integration of estimation scales into clinical and public health strategies.

To explore the association between ethnicity and cardiovascular disease (CVD) risk factors, including physical inactivity, obesity, hypertension, type 2 diabetes (T2D), lack of health insurance and low family income in a nationally representative sample of U.S. adults.

Adults from the National Health and Nutrition Examination Survey (NHANES 2011-2020, n = 17,355) were classified as having CVD risk factors based on both self-reported and metabolic data. Ethnic differences in how these CVD risk factors relate to prevalent CVD and CVD mortality was examined in Whites, Blacks, Asians and Hispanics.

Compared to Whites, significant disparities were noted in several CVD risk factors in ethnic minorities, such as lower PA, lower income, and more prevalent metabolic risk factors. Blacks and Hispanics commonly had higher prevalent CVD risk as compared to Whites even after adjusting for income and metabolic risk factors. Physical inactivity was most strongly associated with prevalent CVD and CVD mortality among Whites and Blacks. There were no ethnic differences in the inverse association between income and prevalent CVD risk, but Blacks with low income were associated with the greatest elevated CVD mortality. Hypertension and T2D were similarly related with prevalent CVD across ethnic groups, but Blacks and Hispanics with hypertension or T2D were at greater CVD mortality risk as compared to Whites.

Our study identified that socioeconomic and metabolic risk factors may relate differently to CVD outcomes among ethnic minority groups in the United States. Addressing these ethnic disparities in health warrants further investigation.

Dyslipidemia is the leading cause of cardiovascular disease (CVD) in Type 2 diabetes mellitus patients. As a result, it is critical to target and manage the level of atherogenic lipids. Angiopoietin-like proteins 3 and 4 (ANGPTL 3 and ANGPTL 4) play an important role in the intravascular lipolysis of triglyceride-rich lipoproteins by blocking the enzyme lipoprotein lipase. This study aimed to determine the amounts of these angiopoietin-like proteins in T2DM and find their association with dyslipidemia in T2DM.

Sixty-one T2DM patients of age group 25-65 years and 27 healthy age-matched control participants were enrolled in the study. Glycemic status (FBS, PPBS, HbA1C), serum lipid parameters (cholesterol, TG, LDL, VLDL, HDL, Tc/HDL ratio), free fatty acid, serum insulin, and ANGPTL3, 4 were measured. A correlation was found between the ANGPTLs and the above parameters in T2DM patients.

Serum ANGPTL3 (P < 0.05) and ANGPTL4 (P < 0.001) were significantly decreased in T2DM. ANGPTL4 was also negatively correlated to PPBS (0.03), HbA1C (P = 0.05), and IR (P = 0.04). However, no such correlation was observed with ANGPTL 3. It was observed that lipid parameters were correlated with ANGPTL3 (LDL (P = 0.03), TC/HDL (P = 0.02)). There was a significant relationship between ANGPTL3 and 4 with FFA (P = 0.001 and P = 0.03, respectively).

This study shows that ANGPTL 3,4 may be associated with dyslipidemia in T2DM. ANGPTL4 is more correlated with glycemic status.

Effective preventive strategies for major adverse cardiovascular events (MACE) in T2DM patients are limited. Recent studies have explored the cardiovascular benefits of N-Acetylcysteine (NAC), an antioxidant with endothelial protective properties. This study investigates the long-term effects of NAC on MACE risk in T2DM patients, focusing on its potential as an adjunctive therapy.

This population-based cohort study used data from Taiwan's National Health Insurance Research Database (NHIRD) and included 46,718 T2DM patients diagnosed between 2008 and 2018, with follow-up until December 31, 2021. Propensity score matching (PSM) ensured balanced comparisons between NAC users and non-users. Cox regression and time-dependent Cox hazards models assessed MACE risk, adjusting for multiple covariates.

In the matched cohort of 23,359 NAC users and 23,359 non-users, NAC users had a significantly lower incidence of MACE (41.74 % vs. 46.87 %, P < .0001). Adjusted Hazard Ratios (aHRs) indicated a consistent protective effect of NAC against overall MACE (aHR: 0.84; 95 % CI: 0.81-0.86, P < .0001). Higher cumulative defined daily doses (cDDD) of NAC correlated with reduced MACE risk, with the highest quartile (Q4) showing an aHR of 0.61 (95 % CI: 0.58-0.64, P < .0001).

This study underscores the significant reduction in MACE risk among T2DM patients with long-term NAC therapy. Notably, the findings emphasize NAC's dose-dependent effectiveness in diminishing MACE incidence, indicating its potential as a valuable adjunctive therapy for managing cardiovascular risk in T2DM patients.

Traditional risk factors cannot accurately predict cardiovascular events (CVE) in type 2 diabetes (T2D). The LIPOCAT study aimed to prospectively evaluate the clinical utility of advanced lipoprotein characteristics and glycoproteins to predict future cardiovascular events (CVE) in a large cohort of subjects with type 2 diabetes mellitus (T2D).

From four different Spanish prospective cohorts, a total of 933 T2D subjects were selected to form the LIPOCAT study. Advanced 1H-Nuclear Magnetic Resonance (1H-NMR) analysis included lipoprotein (Liposcale®) and glycoprotein (Glycoscale) profiling. Random forest classification models and Area Under the Receiver Operating Characteristics (AUROC) analysis were used to assess the differential contribution of advanced variables in predicting CVE. Validation was performed using an external cohort.

Out of 933 T2D subjects, 104 reported a CVE during follow-up. Analysis of Liposcale®/Glycoscale uncovered elevations in the circulating VLDL-cholesterol(C), remnant IDL-triglycerides (TG) and LDL-TG in subjects with CVE, along with glycoproteins (Glyc) A and B. Moreover, the incorporation of advanced Liposcale® variables to a base model constructed with traditional risk factors significantly improved the prediction of CVE, as evidenced by 1.5-fold increase in the C statistic (AUROC), reaching AUROC values of 0.756. In the independent validation cohort, similar improvements in AUROC values were observed by adding the advanced variables to the traditional models.

Advanced 1H-NMR analysis revealed previously hidden lipoprotein and glycoprotein characteristics associated with CVE in T2D subjects.

The Pidanjiangtang (PDJT) formula was founded on the "Pidan" theory from the "Nei Jing." PDJT is considered to eliminate the accumulation of pathological products, remove heat sources, and prevent damage to organs such as the liver and islets. It is widely used in clinical practice to treat impaired glucose tolerance (IGT). However, the bioactive ingredients and underlying mechanisms are still unclear and need further investigation.

This study aimed to determine the therapeutic effect of PDJT on IGT rats and explore the mechanism of PDJT intervention on IGT by four-dimensional independent data acquisition (4D-DIA) proteomics analysis.

The IGT model was established by a high-fat diet combined with Streptozotocin (STZ) injection. The IGT rats were treated with low, medium, and high doses of PDJT orally for 42 days and compared with the Metformin positive control group. The therapeutic effects of PDJT on IGT rats were evaluated using the oral glucose tolerance test (OGTT), serum lipoprotein detection, insulin detection, liver histopathology, and hepatic steatosis assessment. 4D-DIA proteomics analysis was used to explore the differential proteins (DEPs) and potential pathways of PDJT. Finally, Western blotting and ELISA techniques were used to verify DEPs and major targets.

PDJT can enhance glucose metabolism, restore islet β cell function, regulate lipoprotein metabolism, reduce hepatic steatosis, and consequently slow down the progression of IGT. In the proteomic analysis, a total of 355 DEPs were identified, and critical proteins were validated. The results indicated that the JAK2/STAT1 signaling pathway plays a pivotal role in the effects of PDJT. IκB-ζ may be a potential target for PDJT in regulating the inflammatory response of IGT.

PDJT is an effective formula for improving IGT, with its potential mechanism linked to the JAK2/STAT1/IκB-ζ signaling pathway. This study offers a novel approach to investigating the mechanisms of TCM formula through proteomics and offers new insight into exploring TCM treatment for IGT.

Pneumatosis intestinalis (PI) is a rare but significant side effect associated with the use of alpha-glucosidase inhibitor (αGI) in the treatment of diabetes. This study aims to analyze the clinical features of PI induced by αGIs in patients with type 2 diabetes mellitus.

We conducted a retrospective analysis of patients diagnosed with PI between January 2018 and December 2023. Data collected included demographic characteristics, clinical symptoms and signs, laboratory findings, imaging results, endoscopic manifestations, treatments, and outcomes. Clinical characteristics were compared between patients who used acarbose and those who did not.

A total of 48 patients with PI were included in the study, of whom 22 had used acarbose and 26 had not. The acarbose taken group was significantly older than the acarbose untaken group. Additionally, the prevalence of coronary heart disease and hypertension was markedly higher in patients taking acarbose. Importantly, total bilirubin levels were lower in those with PI who were on acarbose therapy.

Our findings highlight the need for increased vigilance regarding the potential development of PI in older diabetic patients with cardiovascular conditions following αGI administration. Timely intervention is crucial to prevent adverse outcomes. This study offers valuable insights for the future management of αGI in diabetes treatment.