Umberto Capece

Diabetic cardiomyopathy (DCM) is a distinct myocardial disorder that develops independently of coronary artery disease and hypertension and represents a major contributor to heart failure in patients with diabetes. Beyond hemodynamic alterations, DCM is driven by complex molecular mechanisms involving metabolic dysregulation, mitochondrial dysfunction, inflammation, and fibrotic remodeling. Increasing evidence identifies oxidative stress as a central integrative process linking these pathogenic pathways in the diabetic heart. Chronic hyperglycemia, insulin resistance, and altered substrate utilization promote excessive generation of reactive oxygen species, overwhelming endogenous antioxidant defenses and disrupting myocardial redox homeostasis. Oxidative stress induces direct damage to lipids, proteins, and DNA while simultaneously activating redox-sensitive signaling pathways that amplify inflammation, endothelial dysfunction, cardiomyocyte apoptosis, and fibrosis. In addition, epicardial and visceral adipose tissue have emerged as active contributors to myocardial oxidative stress through paracrine and systemic mechanisms, reinforcing inflammatory and fibrotic crosstalk. This review provides a comprehensive overview of the molecular sources and targets of oxidative damage in DCM, examines the impairment of antioxidant defense systems, and discusses emerging therapeutic strategies aimed at restoring redox balance.

Background: Euthyroid Sick Syndrome (ESS) is a clinical condition characterized by reduced free triiodothyronine (FT3) levels in response to acute or chronic stress. Proximal femur fractures in geriatric patients are associated with high morbidity and mortality rates and ESS may influence outcomes in this population. This study aimed to investigate the role of ESS as a predictor of complications in elderly patients with hip fractures, analyzing its association with inflammatory and nutritional markers, including the Monocyte-to-Lymphocyte Ratio (MLR), Controlling Nutritional Status (CONUT) score and Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score. Materials and Methods: We conducted a single-center retrospective analysis of patients aged 65 and older who were admitted with proximal femur fractures requiring surgical intervention. Thyroid hormone profiles, inflammatory markers and other clinical variables were analyzed preoperatively (T0) and on the first (T1) and third (T2) postoperative days. Logistic regression was used to identify predictors of complications and transfusion requirements. Results: The study included 103 patients (72 men, 31 women; mean age 85 ± 6.27 years). ESS was present in 30 patients (29%) and was associated with longer surgery duration (83.9 ± 35.5 vs. 68.9 ± 21.3 min; p = 0.042). At admission (T0), ESS patients had lower FT3 (1.91 ± 0.25 vs. 2.75 ± 0.28 pmol/L; p < 0.001) and higher TSH (1.55 ± 0.75 vs. 1.20 ± 0.80 mIU/L; p = 0.057). Postoperatively, MLR was significantly altered at T1 (p = 0.026) and T2 (p = 0.040). ESS was a significant predictor of complications at T0 but lost significance postoperatively, while MLR emerged as a key predictor at T2 (p = 0.003). Logistic regression confirmed MLR at T2 as an independent predictor of complications. Hemoglobin levels at T0 (p < 0.001), T1 (p < 0.001), and T2 (p < 0.001), along with albumin at T1 (2.67 ± 0.34 vs. 2.94 ± 0.33 g/dL; p = 0.001) and calcium at T1 (p = 0.006), were significant predictors of transfusion requirements. Nutritional and inflammatory scores were not predictive. Conclusions: ESS is a significant initial predictor of complications in geriatric patients with hip fractures, but inflammatory markers such as MLR assume greater relevance in the postoperative period. These findings emphasize the importance of monitoring ESS and MLR to enhance risk stratification and guide personalized management strategies.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, impulsivity and/or hyperactivity. In recent years, metabolic alterations, primarily obesity, insulin resistance, and diabetes, have emerged as frequent comorbidities in individuals with ADHD, suggesting a bidirectional relationship between neurodevelopmental and metabolic dysfunctions. Emerging evidence indicates that dysregulation of dopaminergic signaling, disturbances in the hypothalamic-pituitary-adrenal (HPA) axis, and chronic low-grade inflammation are central to both ADHD symptomatology and metabolic impairments. For instance, alterations in dopamine-related genes (e.g., DRD4, DAT1) not only affect cognitive and behavioral functions but also play a role in appetite regulation and glucose homeostasis. Epidemiological studies further demonstrate that individuals with ADHD exhibit poorer glycemic control and a higher prevalence of both type 1 and type 2 diabetes, while early-life metabolic challenges such as maternal diabetes may predispose offspring to ADHD. This review aims to comprehensively synthesize the epidemiological, genetic, and pathogenetic evidence linking ADHD to metabolic alterations. We discuss key pathophysiological pathways—including dopaminergic dysregulation, HPA axis disturbances, inflammation, and oxidative stress—and evaluate their contributions to the co-occurrence of ADHD and metabolic disorders. In addition, we explore the clinical implications and integrated treatment approaches that encompass lifestyle modifications, pharmacological therapies, and multidisciplinary care. Finally, we outline future research directions to develop personalized and holistic interventions.

Omega-3 fatty acids reduce triglycerides and have several positive effects on different organs and systems. They are also found in the plasma membrane in variable amounts in relation to genetics and diet. However, it is still unclear whether omega-3 supplementation can reduce the occurrence of major cardiovascular events (MACEs). Two trials, REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), with highly purified EPA, and STRENGTH (Effect of High-Dose Omega-3 Fatty Acids vs. Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk), with a combination of EPA and DHA, have produced different outcomes, triggering a scientific debate on possible explanations for the discrepancies. Furthermore, doubts have arisen as to the anti-inflammatory and anti-aggregating activity of these compounds. Recent studies have, however, highlighted interesting effects of EPA and DHA on erythrocyte membrane fluidity (EMF). EMF is governed by a complex and dynamic biochemical framework, with fatty acids playing a central role. Furthermore, it can be easily measured in erythrocytes from a blood sample using fluorescent probes. Recent research has also shown that EMF could act as a possible cardiovascular risk factor biomarker. This review aims to synthetize the latest evidence on erythrocyte membrane fluidity, exploring its potential role as a biomarker of residual cardiovascular risk and discussing its clinical relevance. Further, we aim to dissect the possible biological mechanisms that link omega-3 modifiable membrane fluidity to cardiovascular health.

Aims. European registries and retrospective cohorts highlighted the lack of low-density lipoprotein-cholesterol (LDL-C) goal achievement in many very high-risk patients. Hospitalized patients are often frail, and frailty is associated with all-cause mortality and cardiovascular mortality. Aim of this study is to evaluate LDL-C levels in a Real-World setting of inpatients, identify cardiovascular risk categories and highlight treatment gaps in the implementation of LDL-C control. Methods. This retrospective, observational study included all the adult patients admitted at an Italian hospital between 2021-2022 and with LDL-C values available during hospitalization. Disease-related real-world data were collected from Hospital Information Systems using automated data extraction strategies and through the implementation of a patient-centered data repository (the Dyslipidemia Data Mart). Assessment of cardiovascular risk profiles, LDL-C target achievement according to the 2019 ESC/EAS guidelines and lipid-lowering therapies (LLT) use were performed. Results. 13,834 patients were included: 17.15%, 13.72%, 16.82% and 49.76% were low (L), moderate (M), high (H) and very high-risk (VH) patients, respectively. The percentage of in-target patients was progressively lower moving towards worse categories (78.79% in L, 58.38% in M, 33.3% in H and 21.37% in VH). Among LLT treated patients in VH category, in-target are 28.48%; 47.6.% in H, 69.12% in M and 68.47% in L. The impact of monotherapies and combination therapies on target achievement was also analyzed. Conclusions. This study depicts LDL-C control among an entire population of inpatients, highlighting relevant gaps especially in VH category. Future efforts must aim to reduce the cardiovascular risk of these subjects.

Type 2 diabetes mellitus (T2DM) is one of the most widespread diseases worldwide. Lifestyle interventions, including diet and physical activity (PA), are fundamental non-pharmacological components of T2DM therapy. Exercise interventions are strongly recommended for people with or at risk of developing or already with overt diabetes, but adherence to PA guidelines in this population is still challenging. Furthermore, the heterogeneity of T2DM patients, driven by differing residual β-cell functionality, as well as the possibility of practicing different types and intensities of PA, has led to the need to develop tailored exercise and training plans. Investigations on blood glucose variation in response to exercise could help to clarify why individuals do not respond in the same way to PA, and to guide the prescription of personalized treatments. The aim of this review is to offer an updated overview of the current evidence on the effects of different regimens and modalities of PA regarding glucose sensing and β-cell secretory dynamics in individuals with prediabetes or T2DM, with a special focus on β-cell function.

Alpha-lipoic acid (ALA) is a natural compound with antioxidant and pro-oxidant properties which has effects on the regulation of insulin sensitivity and insulin secretion. ALA is widely prescribed in patients with diabetic polyneuropathy due to its positive effects on nerve conduction and alleviation of symptoms. It is, moreover, also prescribed in other insulin resistance conditions such as metabolic syndrome (SM), polycystic ovary syndrome (PCOS) and obesity. However, several cases of Insulin Autoimmune Syndrome (IAS) have been reported in subjects taking ALA. The aim of the present review is to describe the main chemical and biological functions of ALA in glucose metabolism, focusing on its antioxidant activity, its role in modulating insulin sensitivity and secretion and in symptomatic peripheral diabetic polyneuropathy. We also provide a potential explanation for increased risk for the development of IAS.

Objective: Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on whole body insulin sensitivity, myocardial perfusion, and metabolism in patients with T2D without HF. Research design and methods: This was a single-center, prospective, randomized, double-blind controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg) or placebo. Whole body glucose uptake (WBGU) and myocardial glucose uptake (MGU) were measured with PET/CT with FDG during euglycemic hyperinsulinemic clamp. Stress (i.v. adenosine infusion) and resting myocardial blood flow (MBF) and myocardial flow reserve (MFR) were calculated by PET/CT with 13N-ammonia. Results: 16 patients were randomized (8 dapagliflozin; 8 placebo). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). Dapagliflozin significantly improved MFR (2.56±0.26 vs 3.59±0.35) compared with placebo group (2.34±0.21 vs 2.38±0.24; p for interaction =0.001) and was associated to a reduction of resting MBF corrected for cardiac workload (p=0.045). A trend toward an increase in stress MBF was also detected (p=0.058). Moreover, in dapagliflozin group we observed an increase of WBGU of borderline statistical significance (p=0.06) and no effects on MGU (p=0.41). Conclusions: At the best of our knowledge, our study, for the first time, demonstrated that SGLT-2 inhibition increases MFR in T2D patients. The data presented provide a new potential explanation of cardiovascular benefits with SGLT-2i as they make patients more tolerant to the detrimental impact of obstructive coronary atherosclerosis on MFR. Funding Acknowledgement: Type of funding sources: None.