Background/Objectives: Several risk factors have been identified as being involved in the progression of COVID-19 over time. Among these, age, comorbidities, and various laboratory parameters have been reported. Diabetes mellitus is one of the most common comorbidities found among patients diagnosed with SARS-CoV-2 infection. Glucose metabolism dysfunction can exacerbate pre-existing diabetes or even induce diabetes mellitus. The purpose of this study is to assess the accuracy of the CURB-65, PSI, MuLBSTA severity scores and laboratory parameters in patients with diabetes mellitus diagnosed with COVID-19. Methods: We conducted a retrospective study involving patients with diabetes mellitus diagnosed with SARS-CoV-2 infection, performed between June 2023 and December 2024. Results: We analyzed 73 patients with pre-existing diabetes who were diagnosed with COVID-19. There were 56.16% men, living mostly in urban areas, with a median hospital stay of 9.38 days. Elevated levels of LDH (367.50, p = 0.002), CRP (133.90, p = 0.012), ferritin (724.25, p = 0.012), ESR (55.00, p = 0.014), D-dimers (2455.04, p = 0.004), white blood cells (12.76, p = 0.007) and the neutrophil-to-lymphocyte ratio (15.86, p = 0.021) were recorded in the group of deceased patients. Significantly elevated values were recorded for all three severity scores, the AUC for CURB-65 was 0.69, PSI 0.81 and MuLBSTA 0.86. Conclusions: Severity scores showed robust prognostic value in predicting mortality among patients with diabetes mellitus and COVID-19, emphasizing their relevance as clinically applicable tools for risk stratification and outcome assessment.

Background and Objectives: Diabetes mellitus is a major systemic modifier of oral infection, periodontal inflammation, and tissue healing. Persistent hyperglycemia may intensify oxidative stress, immune dysfunction, dysbiotic biofilm activity, and advanced glycation end-product/receptor signaling, thereby reducing the predictability of periapical and periodontal healing. In patients with endo-periodontal lesions, these mechanisms may interact with pulpal infection and periodontal breakdown, complicating diagnosis, prognosis, and therapeutic sequencing. This review summarizes current evidence on diabetes, glycated hemoglobin (HbA1c), and endo-periodontal outcomes and proposes an HbA1c-guided clinical framework for risk stratification and treatment planning. Materials and Methods: A structured narrative review with an expert-informed clinical framework was conducted using the literature published between January 2016 and December 2025. Eligible sources included consensus reports, clinical practice guidelines, systematic reviews, meta-analyses, umbrella reviews, randomized and non-randomized clinical studies, observational studies, and selected mechanistic studies or contemporary narrative reviews with direct relevance to the framework. Case reports, animal studies, and in vitro investigations without direct relevance to the clinical framework were excluded from the main synthesis. Results: Diabetes is associated with increased periodontal severity, impaired periodontal treatment response, a higher prevalence of radiolucent periapical lesions in root-filled teeth, delayed periapical healing, and increased non-retention of endodontically treated teeth. Periodontal therapy is safe in diabetic patients and may be associated with modest reductions in HbA1c, especially when baseline metabolic control is poor. Conclusions: HbA1c should complement, not replace, pulpal testing, periodontal charting, and radiographic assessment. The proposed framework prioritizes endodontic infection control when pulpal necrosis or active intracanal infection is present, adapts periodontal intervention to metabolic risk, and postpones elective surgical or regenerative procedures in poorly controlled diabetes until medical stabilization is achieved.

Epicardial adipose tissue (EAT) is a distinct form of visceral adipose tissue that lies within the pericardium and directly adjacent to the myocardium. Individuals with type 2 diabetes mellitus (T2DM) exhibit excessive and metabolically active EAT, which contributes to the development of early diabetic myocardial disease, formerly referred to as diabetic cardiomyopathy. Recent studies have demonstrated that excess EAT is characterized by a proinflammatory profile that may adversely affect the underlying myocardium, leading to impaired diastolic and systolic function. In this review, we discuss the role of excessive EAT as a source of proinflammatory and profibrotic cytokines that influence adjacent ventricular and atrial myocardium through local tissue crosstalk. In addition to metabolic alterations, enlarged EAT induces hemodynamic changes that result in pericardial constraint and enhanced ventricular interdependence, both of which are hallmarks of diabetic pericardial disease. We further analyze the interplay among T2DM, inflammation, obesity, and increased EAT on the one hand, and myocardial dysfunction characterized by myocardial stiffness, elevated filling pressures, and diastolic and systolic dysfunction on the other. We emphasize that the distinct immunometabolic activity of perivascular adipose tissue may lead to a paradigm shift in the understanding of coronary artery disease, moving from a predominantly endoluminal to an exoluminal perspective. A wide range of dietary, lifestyle, and pharmacological interventions are available within this emerging diabeto-cardiometabolic continuum, each with a potential role; however, the timing of intervention is crucial. This review also explores the potential effects of antidiabetic and other pharmacological agents that modulate EAT thickness, volume, and/or activity, and discusses directions for future mechanistic and clinical research.

Background and Objectives: This retrospective study evaluated patients with diabetes classified according to cluster-derived diabetes phenotype groups and compared their baseline metabolic characteristics, documented complication profiles, and HbA1c course during follow-up. Materials and Methods: A total of 158 patients with type 1 or type 2 diabetes followed at Zonguldak Bülent Ecevit University Endocrinology Outpatient Clinic were included. Phenotype assignment was based on baseline domains corresponding to the Ahlqvist framework: age at diagnosis, BMI category, HbA1c, beta-cell function, insulin resistance, and autoantibody status. Complications were not used for phenotype assignment. Baseline characteristics, binary complication status, exploratory phenotype-contrast logistic regression, and longitudinal HbA1c data were evaluated. Results: The groups showed significant differences in age, age at diagnosis, HbA1c, obesity status, fasting glucose, C-peptide, fasting insulin, HOMA1-%B, HDL cholesterol, ALT, and eGFR. Hepatic steatosis/suspected NAFLD, retinopathy, nephropathy, polyneuropathy, and ketosis/ketoacidosis differed among groups when complications were analyzed as ever-positive versus negative. In exploratory phenotype-contrast logistic regression, Clusters 3-4 were associated with hepatic steatosis/suspected NAFLD, Cluster 2 with retinopathy and polyneuropathy, Cluster 3 with nephropathy, and Clusters 1-2 with ketosis/ketoacidosis; the contrast for coronary artery disease did not reach statistical significance. In a linear mixed-effects model for repeated HbA1c measurements, phenotype group was associated with HbA1c levels, whereas the time effect and group-by-time interaction were not statistically significant. Conclusions: Cluster-derived diabetes phenotype groups showed distinct baseline metabolic characteristics and different documented complication profiles. These findings should be interpreted as exploratory because of the retrospective design and incomplete follow-up data.

Background and Objectives: Physical inactivity is a major modifiable lifestyle factor associated with type 2 diabetes mellitus (T2DM). However, real-world primary care datasets often rely on pragmatic clinical estimates of physical activity (PA) and may lack HbA1c, fasting glucose, dietary data, diabetes duration, and detailed medication information. Therefore, PA-T2DM associations in routine care must be interpreted within the limitations of cross-sectional observational data. Materials and Methods: This cross-sectional observational study analyzed 863 adult patients from a real-world primary care cohort. Participants were categorized into low, moderate, and high PA groups according to self-reported habitual weekly activity levels estimated during routine physician interviews. PA categories were based on clinically meaningful weekly activity thresholds consistent with public health recommendations. The primary outcome was documented T2DM. Secondary variables included lipid profile, blood pressure, body mass index, waist circumference, smoking status, and statin therapy. Multivariable logistic regression models were used to assess associations between PA category and T2DM, with high PA as the reference group. Results: T2DM prevalence showed a graded inverse cross-sectional association across PA categories, being highest in the low PA group (29.7%), intermediate in the moderate PA group (16.7%), and lowest in the high PA group (8.9%) (p < 0.001). In the fully adjusted model, low PA was strongly associated with higher odds of T2DM compared with high PA (odds ratio [OR] 4.32, 95% confidence interval [CI] 2.61-7.15, p < 0.001). Moderate PA was also associated with higher odds of T2DM compared with high PA (OR 2.07, 95% CI 1.23-3.48, p = 0.006). LDL-C differed significantly across PA groups, with the lowest values observed in the high PA group, whereas most other cardiometabolic parameters were comparable. Conclusions: Lower self-reported PA was strongly associated with higher T2DM prevalence after multivariable adjustment in this real-world primary care cohort. These findings support routine PA assessment as part of lifestyle-based cardiometabolic risk stratification. Because dietary intake, HbA1c, diabetes duration, glucose-lowering medication details, and regulatory biomarkers were not available, causal and mechanistic conclusions cannot be drawn. Future studies should integrate PA, nutritional assessment, glycemic markers, medication data, and physiological regulatory measures to better characterize lifestyle-related diabetes risk.

Background and Objectives: Although the association between frailty and constipation in older adults has attracted growing attention, evidence linking the Clinical Frailty Scale (CFS) to colonic transit time (CTT) remains scarce. In this retrospective study, we examined this association using colon capsule endoscopy (CCE). Materials and Methods: We enrolled 124 older adults (64 men, 60 women) aged ≥ 65 years (mean age 74.6 ± 5.6) who underwent CCE for colorectal polyp screening at Aishinkai Nakae Hospital, Japan, between January 2014 and July 2024. CTT was determined at the time of CCE, and frailty was assessed with the Japanese version of the CFS. To avoid the oversimplification inherent in a strict dichotomy, participants were analyzed primarily as three ordered categories-Robust (CFS 1-2; n = 73), Intermediate (CFS 3-4; n = 43), and Frail (CFS 5-7; n = 8)-and, for comparability with previous reports, also as a Robust versus Non-robust (CFS 3-7; n = 51) dichotomy. The independent association between CFS and CTT was examined with three complementary multivariable linear regression models (Model 2: CFS continuous; Model 3: CFS three-category ordinal; Model 3b: CFS three-category dummy with Robust as reference), each adjusted for 10 covariates: age, sex, body mass index, type 2 diabetes mellitus, laxative use, anticholinergic drug use, psychotropic drug use, hypothyroidism, smoking history, and history of abdominal surgery. Results: CTT rose stepwise across the three frailty categories (Robust: 132.0 min [IQR 81.0-229.0], 157.9 ± 99.9; Intermediate: 198.0 min [90.5-267.0], 186.1 ± 99.8; Frail: 241.5 min [199.0-320.5], 295.8 ± 181.3; Kruskal-Wallis p = 0.027; Jonckheere-Terpstra P for trend = 0.017); the dichotomous comparison was concordant (median 214.0 vs. 132.0 min; Mann-Whitney U U = 1441.5; p = 0.033). A graded dose-response-like relationship was further supported by Spearman correlation between the CFS score and CTT (ρ = 0.232; p = 0.009). Women had significantly longer CTT than men (median 189 vs. 121 min; p = 0.013), and the three-group trend was significant within the female subgroup (Kruskal-Wallis p = 0.032) but not within men (p = 0.138). In multivariable analysis, CFS remained independently associated with CTT prolongation both as a continuous score (Model 2: β = 36.6 per 1-point increase; 95% CI 17.3 to 56.0; p < 0.001) and as an ordinal three-category predictor (Model 3: β = 52.7 per one-step advance; 95% CI 19.7 to 85.8; p = 0.002). In the dummy-coded specification (Model 3b), the Frail-versus-Robust contrast was markedly significant (β = 155.4 min; 95% CI 71.5 to 239.3; p < 0.001), whereas the Intermediate-versus-Robust contrast was not (β = 27.0; 95% CI -15.5 to 69.5; p = 0.210). Female sex retained independent significance across models (β ≈ 47-49 min; p = 0.016-0.021). The original dichotomous Non-robust versus Robust specification (Model 1) was no longer significant after full adjustment (p = 0.372). Conclusions: Frailty progression, as assessed by the CFS, is independently and monotonically associated with prolonged CTT in older adults, with the effect becoming statistically manifest predominantly at the more advanced end of the frailty spectrum and particularly in women. Although these findings do not establish causality between frailty and constipation-and frailty itself reflects a multifactorial age-related process that may not be fully reversible-CCE-measured CTT provides an objective, radiation-free physiological biomarker of frailty-related bowel dysfunction that may support risk stratification and inform future interventional trials targeting potentially modifiable components of the gut-muscle axis.

Background and Objectives: The Middle East and North Africa (MENA) region has one of the highest age-standardized diabetes prevalence rates globally, yet all-age, diabetes-specific evidence incorporating GBD 2023 estimates through 2023 remains limited. Materials and Methods: Using Global Burden of Disease (GBD) 2023 estimates for 21 MENA countries from 1990 to 2023, this ecological time-trend analysis quantified 33-year trends in incidence, prevalence, mortality, and disability-adjusted life-years (DALYs); compared pre-2019 and post-2019 trajectories using joinpoint regression; characterized age- and sex-specific burden patterns; and quantified contributions of modifiable risk factors. Results: Age-standardized incidence increased 92%, from 251.7 (95% uncertainty interval [UI]: 231.5 to 272.4) to 482.5 (95% UI: 451.5 to 516.4) per 100,000, and prevalence more than doubled, from 5564 (95% UI: 5088 to 6024) to 11,247 (95% UI: 10,382 to 12,132) per 100,000. In 2023, males exhibited higher DALY rates than females in most adult age groups from age 15 years onward, shifting away from the female-predominant pattern seen in 1990; female rates remained higher at several of the oldest age groups. Children aged 0 to 14 years were the only group with declining DALY rates (-52% to -57%). Post-2019 incidence was higher in 15 of 21 countries, and six countries had higher DALY trends with non-overlapping confidence intervals. Because we only have four to five years of data, these short trends are preliminary and require care when evaluating. High body-mass index was the leading modifiable risk factor. Conclusions: These data support country-specific prevention and chronic-care strategies across the MENA region.

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening condition characterized by elevated pulmonary vascular resistance eventually causing right ventricular failure and premature death. Despite advances in targeted therapies, morbidity and mortality levels remain high, highlighting the need for additional treatment strategies that address the disease's multifactorial pathophysiology. Attention has recently centred on two pharmacological groups with proven roles in other cardiovascular settings: sodium-glucose cotransporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRAs). SGLT2 inhibitors have demonstrated robust clinical benefits in heart failure (HF), type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD), extending survival and reducing hospitalizations. Although their primary actions involve renal glucose and sodium handling, accumulating evidence suggests they may also exert favourable effects on the pulmonary vasculature, endothelial function, and right ventricular performance. In parallel, elevated aldosterone levels have been implicated in vascular remodelling, inflammation, and fibrosis in PAH, suggesting a potential therapeutic role for MRAs. However, the strength and clinical significance of these associations remain under investigation. The aim of this review is to synthesize and critically appraise the current evidence regarding the potential role of SGLT2 inhibitors and MRAs in the treatment of pulmonary arterial hypertension, exploring their mechanistic rationale, preclinical findings, and available clinical data to determine whether these agents may offer additional therapeutic benefit in PAH management.

Background and Objectives: Diabetic kidney disease (DKD) is one of the leading causes of chronic kidney disease (CKD) worldwide. Individuals over 65 years of age with type 2 diabetes mellitus (T2DM) constitute a growing age group that is frequently underrepresented in randomized clinical trials. Finerenone has been shown to reduce renal progression and cardiovascular events in patients with albuminuric DKD. To evaluate the clinical and laboratory characteristics as well as the therapeutic response and safety profile of finerenone in patients over 65 years of age with DKD, based on data from the FINDKDLATAM observational study cohort. Materials and Methods: Subgroup analysis of a real-life, retrospective, multicenter observational study-the FINDKDLATAM cohort. For the present analysis, patients aged ≥ 65 years were stratified. Sociodemographic, clinical, paraclinical, and treatment variables and adverse events were evaluated. The descriptive analysis used medians with interquartile ranges (IQRs) for continuous variables of non-parametric distribution and absolute and relative frequencies for categorical variables. The comparison of baseline parameters and those at six months of follow-up was performed using non-parametric tests, with statistics. Results: Of the total of 347 patients included in the original study, 157 (45.2%) were ≥65 years of age. The median age was 72 years. The baseline profile showed a median glomerular filtration rate (eGFR) of 38.0 mL/min/1.73 m² (IQR: 30.0-50.75), as well as elevated albuminuria (ACR 327.0 mg/g; IQR: 186.5-805.5). In addition, the patients had a high burden of comorbidities. 58.0% of patients received finerenone at a dose of 10 mg and 42.0% at a dose of 20 mg. After six months of follow-up, a significant reduction in the median ACR was observed, decreasing from 327.0 mg/g (IQR: 186.5-805.5) to 78.0 mg/g (IQR: 27.5-143.0), corresponding to a decrease of 76% (p < 0.0001). Regarding safety, hyperkalemia occurred in 20.3% of patients, although, in all cases, it was mild hyperkalemia (potassium between 5.1 and 5.5 mEq/L), with no serious episodes or treatment suspensions attributable to this event. Conclusions: In this cohort of Latin American adults over 65 years of age with albuminuric DKD, finerenone demonstrated good efficiency given the clinically significant reduction of albuminuria with stable renal function at six months of treatment, also demonstrating a safety profile, with a low risk of hyperkalemia.

Background and Objectives: Chronic limb-threatening ischemia (CLTI) represents the most advanced stage of peripheral arterial disease and is associated with an increased risk of major amputation, particularly in patients with diabetes, in whom arterial disease frequently presents with distinct anatomical patterns. While global scores are widely used, the impact of lesion morphology on procedural outcomes is less clearly defined. This study aims to evaluate the distribution of lesion types (stenoses versus occlusions) and their association with the technical success of endovascular revascularization in CLTI, with a focus on differences between diabetic and non-diabetic patients. Materials and Methods: This retrospective study included 136 consecutive patients with chronic limb-threatening ischemia (CLTI) who underwent endovascular revascularization at the Vascular Surgery Department of the "Sf. Spiridon" Clinical Emergency Hospital, Iași, Romania, between May 2021 and May 2023, comprising 85 (62.5%) diabetic and 51 (37.5%) non-diabetic patients. The mean age of the study population was 69.9 ± 9.7 years, and 38 (27.9%) patients were female. Baseline demographic characteristics and major comorbidities were broadly comparable between the two groups. Angiographic lesions were classified according to the degree of luminal narrowing as non-significant stenosis (<50%), significant stenosis (≥50%), or occlusion (complete absence of contrast flow) at the femoropopliteal and infrapopliteal levels. Technical success was defined as restoration of "inline" flow to the leg with residual stenosis < 30%. Patients treated with stenting and those undergoing infrapopliteal angioplasty received short-term (up to 6 weeks) dual antiplatelet therapy. Associations between lesion morphology and procedural outcomes were assessed using appropriate statistical methods. Results: Diabetic patients had more frequent stenotic lesions (55.3% vs. 35.3%, p = 0.024) at the infrapopliteal level, whereas non-diabetic patients had more frequent occlusive lesions (96.1% vs. 83.5%, p = 0.028) at the femoropopliteal level. These differences were associated with procedural outcomes. Occlusive lesions, especially at key anatomical segments, were associated with an increased risk of technical failure, whereas stenotic lesions were more frequently associated with successful endovascular revascularization. Conclusions: Morphological characteristics of lesions play a critical role in determining the success of procedures in CLTI. Stenotic lesions in diabetic patients suggest a distinct vascular phenotype that may influence revascularization strategies. The results highlight the importance of detailed lesion assessment in planning interventions, beyond the use of conventional scores.