Among the complications of diabetes, cardiovascular events and cardiac insufficiency are considered two of the most important causes of death. Experimental and clinical evidence supports the effectiveness of SGLT2i for improving cardiac dysfunction. SGLT2i treatment benefits metabolism, microcirculation, mitochondrial function, fibrosis, oxidative stress, endoplasmic reticulum stress, programmed cell death, autophagy, and the intestinal flora, which are involved in diabetic cardiomyopathy. This review summarizes the current knowledge of the mechanisms of SGLT2i for the treatment of diabetic cardiomyopathy.Graphical Abstract

Background: The Systemic Immune-Inflammation Index (SII), a novel marker of inflammation based on neutrophil, platelet, and lymphocyte counts, has demonstrated potential prognostic value in patients undergoing percutaneous coronary intervention (PCI). Our aim was to assess the correlation between the SII and major adverse cardiovascular events following percutaneous coronary intervention. Methods: We searched PubMed, Web of Science, Embase, and The Cochrane Library from inception to November 20, 2023, for cohort studies investigating the association between SII and the occurrence of MACEs after PCI. Statistical analysis was performed using Revman 5.3, with risk ratios (RRs) and 95% confidence intervals (CIs) as relevant parameters. Results: In our analysis, we incorporated a total of 8 studies involving 11,117 participants. Our findings revealed that a high SII is independently linked to a increased risk of MACEs in PCI patients (RR: 2.08,95%CI: 1.87–2.32, I² = 42%, p < 0.00001). Additionally, we demonstrated the prognostic value of SII in all-cause mortality, heart failure, and non-fatal myocardial infarction. Conclusions: Elevated SII may serve as a potential predictor for subsequent occurrence of MACEs in patients undergoing PCI. Trial registration: Our protocol was registered in PROSPERO (registration number: CRD42024499676).

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders that poses a global threat to human health. It can lead to complications in multiple organs and tissues, owing to its wide-ranging impact on the human body. Diabetic cardiomyopathy (DCM) is a specific cardiac manifestation of DM, which is characterized by heart failure in the absence of coronary heart disease, hypertension and valvular heart disease. Given that oxidative stress is a key factor in the pathogenesis of DCM, intervening to mitigate oxidative stress may serve as a therapeutic strategy for managing DCM. Naringenin is a natural product with anti-oxidative stress properties that can suppress oxidative damage by regulating various oxidative stress signaling pathways. In this review, we address the relationship between oxidative stress and its primary signaling pathways implicated in DCM, and explores the therapeutic potential of naringenin in DCM.

Diabetes-induced myocardial damage leads to diabetic cardiomyopathy and is closely associated with the generation of oxidative stress and inflammation. Naringenin (NG) exhibits antioxidant and anti-inflammatory effects. However, whether NG has cardioprotective effects against diabetic cardiomyopathy by regulating oxidative stress and inflammation remains unknown. This study investigated the effect of NG on diabetic cardiomyopathy based on an analysis of streptozotocin (STZ)-induced type 1 diabetic mice. The results indicated that NG reduced cardiac fibrosis and cardiomyocyte apoptosis in this diabetic model, accompanied by reduced blood glucose. NG inhibited pro-inflammatory cytokines, the level of reactive oxygen species and the expression of nuclear factor kappa-B (NF-κB), whereas the expression of antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) were greatly enhanced by NG. Furthermore, in high glucose-treated H9C2 myocardial cells, NG effectively reduced cell apoptosis by inhibiting the formation of reactive oxygen species and pro-inflammatory cytokines. NG's antioxidant and anti-inflammatory activities were mechanistically associated with NF-κB inhibition and Nrf2 activation in animal and cell experiments. Data analysis showed that NG could regulate Nrf2 and NF-κB pathways to protect against diabetes-induced myocardial damage by reducing oxidative stress and inhibiting inflammation.

Inflammation and fibrosis induced by hyperglycemia are considered to play a critical role in the pathogenesis of diabetic nephropathy. As macrophage polarization may determine the severity and progression of inflammation, regulation of macrophage polarization may be an effective method to treat diabetic complications. Fasudil, a potent Rho-kinase inhibitor, reportedly exhibits anti-inflammatory activity. However, whether fasudil reduces hyperglycemia-induced diabetic nephropathy via regulation of macrophage polarization remains unclear. In this study, we investigate the effect of fasudil on diabetic nephropathy in streptozotocin-induced type 1 diabetic mice. Our data showed that fasudil significantly decreased urinary protein and serum creatinine in diabetic mice, whereas it had no effect on the body weight and blood glucose. We also found increased M1-type macrophages and related proinflammatory cytokines, adverse fibrosis in renal tissue of diabetic mice. Interestingly, treatment of diabetic mice with fasudil increased the number of M2-type macrophages and related anti-inflammatory cytokines, which attenuated renal injury in diabetic mice. Taken together, the results of this study suggest that fasudil could slow the progression of diabetic nephropathy. The possible mechanism might be associated with its induction of M2 macrophage polarization and the reduction of M1 macrophage polarization and inflammation.