To provide insight on targeted approach to mitigate diabetes burden, this research aims to analyze the trends of prevalence, mortality, and disability attributable to risk factors for type 2 diabetes mellitus (T2DM) from 1990 to 2019 in the Southeast Asia (SEA) region. Age-standardized rates for prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) from 1990 to 2019 from the Global Burden of Disease Study were assessed. DALYs-related risk factors were estimated using multivariate regression analysis and estimated annual percentage change (EAPC) was calculated to quantify the temporal trends. Over 30 years, the SEA region experienced a 59.5 % rise in T2DM ASPR, 17.33 % in ASMR, and 26.97 % in DALYs. The T2DM DALYs rate per 100,000 population was 1002.91 (885.23-1132.40) in 1990 and 1273.42 (1103.92-1452.41) in 2019, increasing by 27 %. Cambodia and Indonesia had the highest worsening in three parameters, while most significant improvement in all parameters was observed in Singapore. The curvilinear association was demonstrated between ASMR and DALYs to Gross Domestic Product (GDP) per capita. Prominent risk factors affecting DALYs increase were high fasting plasma glucose (FPG) (p < 0.001), high body mass index (BMI) (p < 0.001), tobacco use (p = 0.012), and household pollution (p = 0.03). Men were more affected than women. The burden of T2DM in the SEA region has increased significantly during the 30-year period. Policymakers should address high BMI, high FPG, smoking, and air pollution to regulate T2DM burden in SEA.

Background: Growth differentiation factor-15 (GDF-15), an emerging biomarker associated with chronic inflammation and oxidative stress, shows potential diagnostic and prognostic significance for heart failure with preserved ejection fraction (HFpEF). This study aimed to assess the diagnostic and prognostic value of GDF-15 in HFpEF. Methods: Three databases (PubMed, Scopus, and ScienceDirect) were used to search for relevant literature published before August 6, 2024. Quality assessment was conducted using the Newcastle-Ottawa scale and its adaptation for cross-sectional studies. Statistical analysis was performed using RStudio version 4.4.1. All meta-analyses employed a random-effects model. Sensitivity analysis was conducted using the leave-one-out technique to evaluate the influence of individual studies on pooled estimates. This study protocol was registered in PROSPERO (CRD42024569609). Results: A total of 5,696 HFpEF patients were identified from 28,193 individuals across 12 observational studies. GDF-15 levels were consistently elevated in HFpEF patients, with a pooled mean difference (MD) of 647.60 pg/mL (95% CI [148.43–1,146.77]; p = 0.01). Sensitivity analysis confirmed the robustness of this finding, with a slightly higher MD observed when studies involving HFpEF patients with atrial fibrillation were excluded. Qualitative analysis suggested that the overall diagnostic performance of GDF-15 in HFpEF is slightly superior to conventional biomarkers. GDF-15 showed a pooled area under the curve (AUC) of 0.82 (95% CI [0.72–0.91]), indicating good diagnostic accuracy. Additionally, GDF-15 was associated with increased risk of all-cause mortality and heart failure hospitalisation, with pooled hazard ratios (HR) of 1.46 (95% CI [1.30–1.62]; p < 0.01) and 1.76 (95% CI [1.30–2.38]; p < 0.01), respectively. Conclusion: GDF-15 demonstrates significant diagnostic and prognostic potential for HFpEF. Elevated GDF-15 levels are associated with increased risk of all-cause mortality and heart failure hospitalisation.

Background: Diabetic retinopathy (DR), a leading cause of vision loss worldwide, is a common complication of type 2 diabetes mellitus (T2DM) driven by chronic hyperglycemia and microvascular damage. Fibroblast growth factor 21 (FGF21) is crucial in blood sugar regulation and has been linked to DR incidence and severity. While some studies suggest that FGF21 levels may contribute to the DR incidence, others propose a protective role. This discrepancy necessitates further analysis, prompting this study to evaluate the association between FGF21 levels and DR incidence and severity in T2DM patients. Methods: A systematic search was conducted through MEDLINE, Web of Science, Scopus, and Embase up to May 2024 for studies evaluating the association between FGF21 and DR incidence and severity. A random-effect model meta-analysis was performed to calculate the pooled standardized mean difference (SMD) and 95% confidence intervals (CI). A univariate meta-regression was performed to analyze factors influencing pooled size estimates. All statistical analyses were performed using STATA 17 software. Result: This systematic review and meta-analysis of 5,852 participants revealed that FGF21 was positively correlated with DR (SMD 3.11; 95% CI [0.92–5.30], p = 0.005) and sight-threatening DR (STDR) incidence (SMD 3.61; 95% CI [0.82–6.41], p = 0.01). There was no significant difference in FGF21 levels in DR vs STDR (p = 0.79). Subgroup analysis revealed a significant difference in DR incidence between LDL groups, with higher DR incidence in the group with low-density lipoprotein (LDL) levels >100 (P < 0.00001). Meta-regression revealed no variables significantly influenced the pooled size estimates. Conclusion: A higher level of FGF21 was associated with higher DR and STDR incidence among T2DM patients, highlighting its potential utilization as a biomarker for DR detection and enabling the exploration of FGF21-based treatment strategies. However, variables independently predicting DR among patients with elevated FGF21 levels shall be explored further. PROSPERO ID: CRD42024559142.

Background: Diabetic retinopathy (DR) is renowned as a prominent cause of visual impairment worldwide. The association between manganese superoxide dismutase (MnSOD) gene, Ala16Val (rs4880), and DR susceptibility in people with type 2 diabetes mellitus (T2DM) remains contentious. Objective: This meta-analysis aims to evaluate risk of DR in T2DM patients with MnSOD Ala16Val polymorphism. Methods: A literature search was conducted using MEDLINE, Scopus, Web of Science, ScienceDirect, EMBASE, and grey literature to identify potential studies assessing the link between MnSOD polymorphism and DR risk among T2DM patients. The data was further analyzed in fixed/random effect models using RevMan 5.3 under five genetic models. Results: Six studies comprising 2,132 subjects from four distinct ethnicities were included. The present study revealed that MnSOD gene polymorphism was associated with a significantly increasing DR risk in T2DM patients under the co-dominant model (VV vs. AA) (OR 1.87 [1.42, 2.46], p<0.0001) and dominant model (VV+AV vs. AA) (OR 1.85 [1.02, 3.33], p=0.0400). Conclusions: T2DM individuals with rs4880 VV alleles are more susceptible to DR development, making them as a potential marker for heightened DR susceptibility in T2DM patients, laying the foundation for a gene panel to assess their susceptibility to develop DR.

Heart failure (HF) remains a leading cause of global mortality, underscoring the urgent need for reliable, minimally invasive biomarkers to facilitate early diagnosis and risk stratification. MicroRNA-21 (miR-21) has been implicated in cardiac fibrosis, hypertrophy, and the progression of HF; however, its clinical utility remains uncertain. This study presents a systematic review and diagnostic test accuracy (DTA) meta-analysis aimed at assessing the diagnostic and prognostic performance of circulating miR-21 in HF. We estimated pooled sensitivity, specificity, and area under the curve (AUC) for the DTA analysis, and synthesized hazard ratios (HRs) with 95% confidence intervals (CIs) for prognostic outcomes. Additionally, univariate meta-regression was conducted to explore demographic and clinical moderators. Our analysis included fourteen studies with a total of 1,327 participants. Results demonstrated that circulating miR-21 levels were significantly elevated in HF patients compared to controls (fold change 1.61; 95% CI 1.46–1.78; p < 0.001). The diagnostic accuracy was notably high, with a sensitivity of 0.94 (95% CI 82.0–98.0), specificity of 0.90 (95% CI 79.0–96.0), and AUC of 0.97 (95% CI 96.0–98.0). Elevated levels of miR-21 were associated with an increased risk of worsening HF severity (HR 1.84; 95% CI 1.14–2.97; p=0.01) and HF-related cardiovascular death (HR 2.00; 95% CI 1.30–3.03; p=0.001). However, no significant association was found with HF-related hospitalization (HR 0.97; 95% CI 0.61–1.52; p=0.88). Variability in sample type and differing clinical thresholds contributed to heterogeneity across studies. These findings support the potential of circulating miR-21 as a diagnostic and prognostic biomarker for HF. Nevertheless, further research with standardized sample sizes and clinical thresholds is necessary to establish robust evidence for its clinical application.

Despite increased awareness of sex differences in cardiovascular disease (CVD), disparities in sex-specific platelet biology and antithrombotic studies are still underexplored. Moreover, women are frequently underrepresented in clinical trials, with numerous research initiatives primarily focusing on estrogen while neglecting non-hormonal influences that contribute variations in thrombotic risk and treatment outcomes. We conducted a literature review to examine sex-related differences in platelet biology, such as elevated platelet counts and reactivity in females, along with distinct expression of receptors and signaling molecules. These variations influence responses to antiplatelet medications—including aspirin, P2Y12 inhibitors, and glycoprotein IIb/IIIa inhibitors, and dual antiplatelet therapy—leading to altered effectiveness and a heightened bleeding risk in women. This review emphasizes the importance of non-hormonal factors, such as transcriptomic and proteomic variations, and highlights the growing potential of omics and systems biology in identifying therapeutic targets specific to sex. Incorporating sex as a biological factor in preclinical and clinical research is crucial for enhancing risk assessment and treatment results. Keyword : Antithrombotic Therapy; Cardiovascular Disease; Platelet; Sex Difference.