Neural tone and cardio-renal outcomes in patients with type 2 diabetes mellitus: a review of the literature with a focus on SGLT2 inhibitors

Nashawi, Mouhamed; Sheikh, Omar; Battisha, Ayman; Ghali, Abdullah; Chilton, Robert

doi:10.1007/s10741-020-10046-w

Cited by 11 publications

(8 citation statements)

References 80 publications

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“…Tang et al reported antioxidant and antiinflammatory effects of Dapa with subsequent inhibition of glomerulosclerosis and liver fibrosis in db/db mice (37). In T2DM patients, Dapa administration resulted in beneficial outcomes pertaining to the microvascular sequelae including improvement of the renal resistive index, arterial stiffness, and systemic endothelial function (38,39). With respect to Lira, it has been found to slow down memory function decline (40), improve cardiovascular and kidney outcomes, and reduce mortality in T2DM patients (41).…”

Section: Discussionmentioning

confidence: 99%

Role of Dapagliflozin and Liraglutide on Diabetes-Induced Cardiomyopathy in Rats: Implication of Oxidative Stress, Inflammation, and Apoptosis

et al. 2022

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The current study aims to assess the protective effects of dapagliflozin (Dapa; a sodium-glucose cotransporter-2 inhibitor) and/or liraglutide (Lira; a glucagon-like peptide 1 agonist) in an experimental model of diabetic cardiomyopathy (DCM). A single dose of streptozotocin (STZ) was administrated to male Sprague–Dawley rats by intraperitoneal injection at a dose of 50 mg/kg to induce diabetes mellitus (DM). Dapa (1 mg/kg, orally), Lira (0.4 mg/kg, s.c.), and Dapa–Lira combination were administrated for 8 weeks once-daily. Blood samples were evaluated for glucose level and biochemical markers of cardiac functions. Cardiac tissue was dissected and assessed for redox homeostasis (malondialdehyde (MDA), glutathione (GSH), and catalase (CAT)), pro-inflammatory mediators (NF-κB and tumor necrosis factor-α (TNF-α)), and apoptotic effectors (caspase-3). Moreover, the effect of treatments on the cardiac cellular structure was studied. Dapa and/or Lira administration resulted in significant improvement of biochemical indices of cardiac function. Additionally, all treatment groups demonstrated restoration of oxidant/antioxidant balance. Moreover, inflammation and apoptosis key elements were markedly downregulated in cardiac tissue. Also, histological studies demonstrated attenuation of diabetes-induced cardiac tissue injury. Interestingly, Dapa–Lira combination treatment produced a more favorable protective effect as compared to a single treatment. These data demonstrated that Dapa, Lira, and their combination therapy could be useful in protection against DM-accompanied cardiac tissue injury, shedding the light on their possible utilization as adjuvant therapy for the management of DM patients.

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Section: Discussionmentioning

confidence: 99%

Role of Dapagliflozin and Liraglutide on Diabetes-Induced Cardiomyopathy in Rats: Implication of Oxidative Stress, Inflammation, and Apoptosis

et al. 2022

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“…Hence, diabetic nephropathy [55], cardiomyopathy [56], retinopathy [57], and diabetic foot infection [58] are well-known adverse outcomes. Furthermore, vagus nerve atrophy may occur as an outcome of neuronal, autoimmune damage, and oxidative stress [59]. DM is connected to various musculoskeletal ailments, such as joint stiffness, gouty arthritis, osteoarthritis, rheumatoid arthritis, and diabetic amyotrophy [60].…”

Section: Complications Of Dmmentioning

confidence: 99%

Therapeutic Screening of Herbal Remedies for the Management of Diabetes

2021

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The study of diabetes mellitus (DM) patterns illustrates increasingly important facts. Most importantly, they include oxidative stress, inflammation, and cellular death. Up to now, there is a shortage of drug therapies for DM, and the discovery and the development of novel therapeutics for this disease are crucial. Medicinal plants are being used more and more as an alternative and natural cure for the disease. Consequently, the objective of this review was to examine the latest results on the effectiveness and protection of natural plants in the management of DM as adjuvant drugs for diabetes and its complex concomitant diseases.

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“…Investigations into the mitochondrial physiology has shown that oxidative stress, as seen in patients with T2DM, can exacerbate phosphate mediated toxicity and cause insulin and glucose dysregulation[ 92 ]. Mitochondrial deficits are the central theme in reactive oxygen species (ROS) formation belief in which by hyperglycemia mediates ROS formation, which impacts nodes of cardiorenal significance[ 35 ].…”

Section: Phosphate Metabolism Diabetes Heart Disease- Loading Sglt2 In the Picturementioning

confidence: 99%

“…SLGT2i also promote cardiovascular benefits in patients with T2DM through auxiliary avenues deeply rooted in diabetic sequelae such as through the blunting of harmful reactive oxygen species (ROS), modulating detrimental neurohormonal activation, improving oxygen flux, and preserving a positive vascular biology profile[ 35 - 38 ]. However, since the capacity for SGLT2i agents hinder the cotransport and reabsorption of sodium and glucose, the sodium gradient is therefore retained for sodium-dependent phosphate cotransporters (SLC34A1 and SLC34A3) as referenced in Figure 2 [ 39 - 41 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular benefits from SGLT2 inhibition in type 2 diabetes mellitus patients is not impaired with phosphate flux related to pharmacotherapy

Nashawi¹,

Ahmed²,

Amin³

et al. 2021

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The beneficial cardiorenal outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) have been substantiated by multiple clinical trials, resulting in increased interest in the multifarious pathways by which their mechanisms act. The principal effect of SGLT2i (-flozin drugs) can be appreciated in their ability to block the SGLT2 protein within the kidneys, inhibiting glucose reabsorption, and causing an associated osmotic diuresis. This ameliorates plasma glucose elevations and the negative cardiorenal sequelae associated with the latter. These include aberrant mitochondrial metabolism and oxidative stress burden, endothelial cell dysfunction, pernicious neurohormonal activation, and the development of inimical hemodynamics. Positive outcomes within these domains have been validated with SGLT2i administration. However, by modulating the sodium-glucose cotransporter in the proximal tubule (PT), SGLT2i consequently promotes sodium-phosphate cotransporter activity with phosphate retention. Phosphatemia, even at physiologic levels, poses a risk in cardiovascular disease burden, more so in patients with type 2 diabetes mellitus (T2DM). There also exists an association between phosphatemia and renal impairment, the latter hampering cardiovascular function through an array of physiologic roles, such as fluid regulation, hormonal tone, and neuromodulation. Moreover, increased phosphate flux is associated with an associated increase in fibroblast growth factor 23 levels, also detrimental to homeostatic cardiometabolic function. A contemporary commentary concerning this notion unifying cardiovascular outcome trial data with the translational biology of phosphate is scant within the literature. Given the apparent beneficial outcomes associated with SGLT2i administration notwithstanding negative effects of phosphatemia, we discuss in this review the effects of phosphate on the cardiometabolic status in patients with T2DM and cardiorenal disease, as well as the mechanisms by which SGLT2i counteract or overcome them to achieve their net effects. Content drawn to develop this conversation begins with proceedings in the basic sciences and works towards clinical trial data.

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Neural tone and cardio-renal outcomes in patients with type 2 diabetes mellitus: a review of the literature with a focus on SGLT2 inhibitors

Cited by 11 publications

References 80 publications

Role of Dapagliflozin and Liraglutide on Diabetes-Induced Cardiomyopathy in Rats: Implication of Oxidative Stress, Inflammation, and Apoptosis

Role of Dapagliflozin and Liraglutide on Diabetes-Induced Cardiomyopathy in Rats: Implication of Oxidative Stress, Inflammation, and Apoptosis

Therapeutic Screening of Herbal Remedies for the Management of Diabetes

Cardiovascular benefits from SGLT2 inhibition in type 2 diabetes mellitus patients is not impaired with phosphate flux related to pharmacotherapy

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