Cardiovascular Diseases and Type 2 Diabetes: 2nd Edition

Background and Objectives: Diabetes mellitus (DM) has been consistently linked to severe coronavirus disease 2019 (COVID-19) and adverse outcomes; however, the extent to which DM independently predicts mortality and cardiovascular complications in real-world hospitalized cohorts remains debated, particularly in Eastern Europe. This study aimed to evaluate the impact of DM on cardiovascular complications and in-hospital outcomes among adults hospitalized with SARS-CoV-2 infection. Materials and Methods: We conducted a single-center retrospective observational cohort study including consecutive adult patients hospitalized with laboratory-confirmed SARS-CoV-2 infection between March 2020 and December 2024 at the “Victor Babeș” Clinical Hospital of Infectious Diseases and Pneumophthisiology, Timișoara, Romania. DM status (type 1, type 2, or newly diagnosed diabetes) was defined using structured dataset fields. The primary outcome was in-hospital all-cause mortality. Secondary outcomes included ICU admission, length of stay, pulmonary embolism (PE) on CT pulmonary angiography (CTPA), and a composite of in-hospital cardiovascular/thromboembolic complications. Multivariable logistic regression models adjusted for clinically relevant covariates (age, sex, BMI, vaccination status, hypertension, ischemic heart disease, atrial fibrillation, prior ischemic stroke, and admission creatinine). Results: A total of 395 patients were included; 98 (24.8%) had DM. Diabetic patients exhibited a high cardiometabolic burden (arterial hypertension: 83.7% vs. 77.4%, p = 0.242) and higher admission renal markers (urea: 55.6 [41.0–79.1] vs. 48.6 [39.2–68.0] mg/dL, p = 0.047; creatinine: 1.04 [0.76–1.52] vs. 0.88 [0.59–1.33] mg/dL, p = 0.008). In-hospital mortality was numerically higher in DM (9.2% vs. 6.7%, p = 0.560), as was ICU admission (7.1% vs. 4.7%, p = 0.503), without statistical significance. PE on CTPA occurred in 13.3% of DM vs. 11.4% of non-DM patients (p = 0.763). In univariable analysis, DM was not significantly associated with mortality (OR 1.40, 95% CI 0.62–3.19; p = 0.422) or ICU admission (OR 1.55, 95% CI 0.61–3.97; p = 0.356). After multivariable adjustment, DM remained not independently associated with mortality (adjusted OR 1.09, 95% CI 0.42–2.83; p = 0.854) or ICU admission (adjusted OR 1.19, 95% CI 0.42–3.36; p = 0.747). Conclusions: In this real-world Eastern European cohort of hospitalized adults with SARS-CoV-2 infection, diabetes mellitus was common and associated with significantly worse renal function at admission, but it was not statistically associated with in-hospital mortality or ICU admission after multivariable adjustment; however, the limited number of events and low events-per-variable raise concerns about model stability and potential false-negative findings. These findings support a risk-marker model in which adverse COVID-19 outcomes in diabetic patients are driven primarily by clustered vulnerability and organ dysfunction rather than diabetes status alone. Full article

Background and Objectives: Diabetes mellitus (DM) is a major risk factor for cardiovascular diseases (CVD), including acute myocardial infarction (MI), and is frequently associated with cardiac autonomic neuropathy (CAN). Post-MI autonomic dysfunction contributes to adverse outcomes, but data on prognostic markers in diabetic patients remain limited. This study aimed to (1) compare autonomic nervous system (ANS) function between patients with MI and DM (MI/DM), MI without DM, and DM without MI; (2) assess differences in MI/DM patients based on survival status; and (3) identify prognostic factors for all-cause mortality in diabetic patients following MI. Materials and Methods: This retrospective–prospective study included 375 patients: 93 MI/DM, 229 MI, and 53 DM. MI patients were treated with fibrinolytic or conservative therapy. All participants underwent cardiovascular reflex tests (CARTs) and 24 h Holter ECG with heart rate variability (HRV) analysis; DM patients without MI were tested in an outpatient setting. The primary endpoint was all-cause mortality during a median follow-up of 38 months. Univariable and multivariable Cox regression analyses were performed to determine mortality predictors. Results: Autonomic dysfunction was prevalent in all groups, with MI/DM patients showing the most pronounced impairment, particularly in parasympathetic function. MI/DM patients had significantly lower SDNN values and higher prevalence of definite parasympathetic dysfunction than other groups. In the MI/DM group, abnormal Valsalva maneuver (VM) was more frequent among non-survivors. Multivariable analysis identified abnormal VM and NSTEMI as predictors of overall mortality. Conclusions: Diabetic patients after MI exhibit the most severe autonomic impairment, predominantly parasympathetic, which may contribute to their increased cardiovascular risk. In this high-risk group, abnormal VM and NSTEMI presentations independently predict long-term mortality. Assessment of autonomic function, particularly VM, may provide valuable prognostic information and aid in risk stratification. Full article

Background and Objectives: Indoxyl sulfate (IS), a gut microbiota-derived metabolite of tryptophan, is implicated in vascular dysfunction through oxidative stress and inflammation. This study evaluated the association between serum IS levels and aortic stiffness (AS) in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: This cross-sectional study enrolled 80 patients with T2DM from a medical center in eastern Taiwan, excluding patients with malignancy, acute infection, heart failure, or recent cardiovascular events. Serum IS concentrations were quantified using liquid chromatography–mass spectrometry. AS was assessed using carotid–femoral pulse wave velocity (cfPWV), with values > 10 m/s indicating AS. Results: A total of 30 patients (37.5%) had AS. IS levels were significantly higher in the AS group than in the control group (p < 0.001). After multivariate adjustment, IS remained an independent predictor of AS (odds ratio: 2.565, 95% confidence interval: 1.145–5.748, p = 0.022). Linear regression analysis confirmed IS as an independent contributor to cfPWV values (β = 0.261, p = 0.019). Receiver operating characteristic analysis showed fair discriminatory ability (area under the curve = 0.739, p < 0.001). Conclusions: In patients with T2DM, serum IS is an independent predictor of AS and may serve as a promising nontraditional biomarker for cardiovascular risk stratification. Full article

Background and Objectives: Type 2 diabetes (T2DM) substantially increases cardiovascular risk; beyond the well-recognized left-ventricular involvement in diabetic cardiomyopathy, emerging data indicate subclinical right-ventricular (RV) dysfunction may also be present. This study aimed to evaluate whether speckle-tracking echocardiography identifies subclinical right-ventricular systolic dysfunction in type 2 diabetes, despite normal conventional indices and preserved global systolic function. Materials and Methods: We conducted a cross-sectional, single-center study in accordance with STROBE recommendations, enrolling 77 participants, 36 adults with T2DM, and 41 non-diabetic controls, between December 2024 and July 2025. All participants underwent comprehensive transthoracic echocardiography, including conventional parameters (tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TV S’), right ventricular fractional area change (RVFAC)) and deformation imaging (right ventricular global longitudinal strain (RV GLS), right ventricular free wall longitudinal strain (RVFWS)) using speckle-tracking echocardiography. Biochemical and clinical data, including glycosylated hemoglobin (HbA1c), were recorded. Correlation and ROC curve analyses were performed to explore associations and predictive value. Results: The mean age was comparable between the two groups (62.08 ± 9.54 years vs. 60.22 ± 13.39 years; p = 0.480). While conventional RV parameters did not differ significantly between groups, diabetic patients had significantly lower RV GLS (−13.86 ± 6.07% vs. −18.59 ± 2.27%, p < 0.001) and RVFWS (−15.64 ± 4.30% vs. −19.03 ± 3.53%, p < 0.001). HbA1c levels correlated positively with RV strain impairment (RVFWS r = 0.41, p < 0.001). Both RV GLS and RVFWS were independent predictors of RV dysfunction in logistic regression analysis. ROC analysis showed good diagnostic performance for RV GLS, AUC = 0.84 with an optimal cut-off −17.2% (sensitivity 86.1% and specificity 80.5%) and RVFWS, AUC = 0.76 with cut-off −17.6% (sensitivity 77.8; specificity 80.5%) in identifying early myocardial involvement. Conclusions: RV systolic dysfunction may occur early in T2DM, even when traditional echocardiographic indices remain within normal limits. Speckle-tracking echocardiography, particularly RV GLS and RVFWS, offers sensitive detection of subclinical myocardial impairment, reinforcing its value in early cardiovascular risk stratification among diabetic patients. Full article

Background and Objectives: Type 2 diabetes mellitus (T2DM) is associated with subclinical cardiovascular changes, such as increased arterial stiffness and myocardial dysfunction. Vitamin D deficiency has been recognized as a potential contributing factor to vascular disease; however, its impact on early cardiac changes associated with T2DM remains poorly understood. Our aim was to evaluate the association between serum levels of 25-hydroxyvitamin D3 [25(OH)D3], arterial stiffness, and left ventricular global longitudinal strain (LV GLS) in patients with T2DM who do not have a clinically evident cardiovascular disease. Material and methods: This cross-sectional study evaluated the carotid intima–media thickness (IMT), aortic pulse wave velocity (PWVao), LV GLS, and serum 25(OH)D3 levels in patients diagnosed with T2DM (n = 65) compared to healthy control subjects (n = 55). Independent predictors of arterial stiffness were identified by a multivariate logistic regression analysis. Results: Patients with T2DM showed a significant increase in IMT and PWVao, a reduction in LV GLS, and low levels of 25(OH)D3 compared to subjects in the control group (all p < 0.05). Both vitamin D deficiency and T2DM were found to be independently associated with an increased arterial stiffness, with odds ratios of 2.4 and 4.8, respectively. A significant inverse relationship was identified between 25(OH)D3 levels and markers of arterial stiffness, as well as LV GLS, suggesting a possible association between the vitamin D status and the early onset of cardiovascular dysfunction. Conclusions: Patients with T2DM show early signs of heart and blood vessel problems, even with an ejection fraction that remains within normal limits. There is a significant correlation between vitamin D deficiency and increased arterial stiffness, along with impaired LV GLS, indicating its possible involvement in cardiovascular complications associated with diabetes. These findings support the utility of integrating vascular, myocardial, and vitamin D assessments in early cardiovascular risk stratification for T2DM patients. Full article

Background and Objectives: Endothelial dysfunction (ED) and oxidative stress play major contributions in the initiation and progression of atherosclerosis. Diabetes is a pathological state associated with endothelial damage and enhanced oxidative stress. This study evaluated endothelial dysfunction and oxidative stress in patients with severe coronary artery disease (CAD) undergoing coronary artery bypass graft (CABG) surgery, comparing those with and without type 2 diabetes mellitus (T2DM). Materials and Methods: We included 84 patients with severe coronary artery disease (33 of whom had type 2 diabetes mellitus) who underwent clinical assessments, ultrasound, and coronaryangiography. The SYNTAXI score was calculated from the coronaryangiogram. Blood samples were collected to measure plasma serotonin (5-HT; SER) levels, as well as levels of superoxide dismutase 1(SOD-1) and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) to assess oxidative stress. Brachial flow-mediated dilation (FMD) was used as a surrogate for endothelial dysfunction (ED),along with serum concentrations of 5-HT. Results: The coronary atherosclerotic burden, assessed using the SYNTAX I score, was more severe in patients with CAD and associated T2DM compared to those with CAD without T2DM (30.5 (17–54) vs. 29 (17–48); p = 0.05). The SYNTAX score was found to be positively correlated with T2DM (p = 0.029; r = 0.238).ED measured by FMD was associated with T2DM (p = 0.042; r = −0.223), with lower FMD measurements in T2DM patients when compared with individuals without this pathology (2.43% (0.95–5.67) vs. 3.46% (1.02–6.75); p = 0.079). Also, in the studied population, T2DM was correlated with serum 5-HT levels (764.78 ± 201 ng/mL vs. 561.06 ± 224 ng/mL; p < 0.001; r = 0.423), with higher plasma circulating levels of 5-HT in patients with T2DM. No statistically significant differences for oxidative stress markers (SOD-1 and LOX-1) were obtained when comparing T2DM and non-T2DM patients with severe CAD. Conclusions: ED (as assessed by brachial FMD and serum 5-HT) is more severe in in diabetic patients with severe CAD scheduled for CABG surgery, while oxidative stress (as evaluated through serum SOD-1 and LOX-1 concentrations) was not influenced by the presence of T2DM in this specific population. The most important finding of the present study is that circulating 5-HT levels are markedly influenced by T2DM. 5-HT receptor-targeted therapy might be of interest in patients undergoing CABG, but further studies are needed to confirm this hypothesis. Full article

Background and Objectives: Diabetes represents a major public health challenge due to its strong link to cardiovascular risk, therefore the aim was to explore the excessive cardiovascular risk attributed to diabetes. Materials and Methods: This cross-sectional study was based on data from the European Health Interview Surveys in Hungary. Propensity score matching was used to control confounding factors including age, gender, education, marital status, income, health status, obesity, smoking, place of residence, and physical activity. Results: A total of 15,874 individuals were analyzed, of whom 1447 (9.12%) reported having diabetes. Furthermore, diabetes was significantly associated with higher prevalence rates of hypertension (by 23.4%), arrhythmia (by 3.85%), heart attack (by 3.42%), and coronary artery disease (by 6.92%) after adjusting for potential confounders. Conclusions: These findings highlight the importance of managing cardiovascular risk factors in individuals with diabetes. Full article

Background: Diabetic retinopathy (DR) is a leading cause of blindness in patients with type 2 diabetes mellitus (T2DM). Cardiovascular risk factors, such as hypertension, obesity, and dyslipidemia, may play a crucial role in the development and progression of DR, though the evidence remains mixed. This study aimed to assess cardiovascular risk factors as independent predictors of DR and to develop a predictive model for DR progression in T2DM patients. Methods: A retrospective cross-sectional study was conducted on 377 patients with T2DM who underwent a comprehensive eye exam. Clinical data, including blood pressure, lipid profile, BMI, and smoking status, were collected. DR staging was determined through fundus photography and classified as No DR, Non-Proliferative DR (NPDR), and Mild, Moderate, Severe, or Proliferative DR (PDR). A Multivariate Logistic Regression was used to evaluate the association between cardiovascular risk factors and DR presence. Several machine learning models, including Random Forest, XGBoost, and Support Vector Machines, were applied to assess the predictive value of cardiovascular risk factors and identify key predictors. Model performance was evaluated using accuracy, precision, recall, and ROC-AUC. Results: The prevalence of DR in the cohort was 41.6%, with 34.5% having NPDR and 7.1% having PDR. A multivariate analysis identified systolic blood pressure (SBP), LDL cholesterol, and body mass index (BMI) as independent predictors of DR progression (p < 0.05). The Random Forest model showed a moderate predictive ability, with an AUC of 0.62 for distinguishing between the presence and absence of DR XGBoost showing a better performance, featuring a ROC-AUC of 0.68, while SBP, HDL cholesterol, and BMI were consistently identified as the most important predictors across models. After tuning, the XGBoost model showed a notable improvement, with an ROC-AUC of 0.72. Conclusions: Cardiovascular risk factors, particularly BP and BMI, play a significant role in the progression of DR in patients with T2DM. The predictive models, especially XGBoost, showed moderate accuracy in identifying DR stages, suggesting that integrating these risk factors into clinical practice may improve early detection and intervention strategies for DR. Full article

Background and Objectives: Dysglycemia is a major determinant of adverse outcomes in COVID-19, yet the separate contributions of poor glycemic control and glycemic variability (GV) remain incompletely defined. We conducted a systematic review and meta-analysis of observational cohort studies (both prospective and retrospective) to quantify the impact of chronic hyperglycemia and glucose instability on disease severity, intensive care requirements, and mortality in patients with COVID-19. Materials and Methods: We searched PubMed, Scopus, and Web of Science from January 2020 to October 2024 for observational cohort studies reporting clinically relevant COVID-19 outcomes stratified by glycemic control or GV. Dysglycemia definitions varied across studies (HbA1c-based chronic hyperglycemia, fasting glucose, or admission/in-hospital hyperglycemia). GV was assessed using metrics including mean amplitude of glycemic excursions (MAGE), standard deviation (SD), coefficient of variation (CV), or maximum daily glucose difference. Twelve studies met inclusion criteria and were included in qualitative synthesis; five studies were eligible for quantitative synthesis of clinical outcomes. Random-effects DerSimonian–Laird models were applied due to anticipated clinical heterogeneity. Heterogeneity was evaluated using Cochran’s Q, τ², and I² statistics. Results: Overall, 12 observational studies (9 prospective and 3 retrospective cohorts; n = 1,008,310 patients) were included. In quantitative analyses of five eligible cohorts, poor glycemic control was associated with a significantly increased risk of severe or critical COVID-19 (pooled RR = 1.75, 95% CI: 1.45–2.11; I² = 29%), ICU admission (RR = 1.54, 95% CI: 1.18–2.01), and mechanical ventilation (RR = 1.72, 95% CI: 1.31–2.26). Three studies evaluating GV demonstrated a strong association with adverse outcomes (pooled RR = 2.07, 95% CI: 1.71–2.50; I² = 0%); this low heterogeneity should be interpreted cautiously given the limited number of studies. GV remained associated with mortality in multivariable models, indicating that glycemic variability is separately associated with mortality as a clinically relevant prognostic risk marker in hospitalized COVID-19 patients. Conclusions: Both chronic hyperglycemia and elevated glycemic variability are each associated with increased risk of severe COVID-19 outcomes. Glycemic variability appeared to be a consistent, low-heterogeneity prognostic marker of mortality, being separately associated with higher death risk in hospitalized COVID-19 patients, highlighting its potential utility as a dynamic metabolic biomarker. Early identification and targeted management of dysglycemia—especially glucose instability—may improve prognosis in hospitalized COVID-19 patients. PROSPERO: CRD420251250718. Full article