The global prevalence of diabetes continues to increase partly due to rapid urbanization and an increase in the aging population. Consequently, this is associated with a parallel increase in the prevalence of diabetic vascular complications which significantly worsen the burden of diabetes. For these diabetic vascular complications, there is still an unmet need for safe and effective alternative/adjuvant therapeutic interventions. There is also an increasing urge for therapeutic options to come from natural products such as plants. Hyperglycemia-induced oxidative stress is central to the development of diabetes and diabetic complications. Furthermore, oxidative stress-induced inflammation and insulin resistance are central to endothelial damage and the progression of diabetic complications. Human and animal studies have shown that polyphenols could reduce oxidative stress, hyperglycemia, and prevent diabetic complications including diabetic retinopathy, diabetic nephropathy, and diabetic peripheral neuropathy. Part of the therapeutic effects of polyphenols is attributed to their modulatory effect on endogenous antioxidant systems. This review attempts to summarize the established effects of polyphenols on endogenous antioxidant systems from the literature. Moreover, potential therapeutic strategies for harnessing the potential benefits of polyphenols for diabetic vascular complications are also discussed.

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Antioxidant Phytochemicals as Potential Therapy for Diabetic Complications

Klotho G395A variants are associated with T2DM and diabetic nephropathy and influence on the levels of biochemical parameters

Diabetes mellitus is a disease that plagues all countries in the world. One of the affectations caused by this chronic disease is damage to peripheral nervous tissues. This is the cause of ulcers and amputations in parts of the foot of the diabetic patient. In this paper, we propose a method to evaluate the patient’s degree of preventive management of peripheral diabetic neuropathy. For this purpose, the Neutrosophic Analytic Hierarchy Process (AHP) method is used to assess the importance of factors influencing the prevention of peripheral neuropathic complications associated with diabetes mellitus in some patients. For the final evaluation, the aggregator called neutrosophic uninorm is used; especially, the operator based on the combining function utilized in the Prospector expert system.

Assessment of the preventive management of peripheral diabetic neuropathy by using neutrosophic AHP and neutrosophic uninorm operator

Peripheral nerve degeneration (PND) is a preparative process for peripheral nerve regeneration and is regulated by Schwann cells, a unique glial cell in the peripheral nervous system. Dysregulated PND induces irreversible peripheral neurodegenerative diseases (e.g., diabetic peripheral neuropathy). To develop novel synthetic drugs for these diseases, we synthesized a set of new cinnamaldehyde (CAH) derivatives and evaluated their activities in vitro, ex vivo, and in vivo. The 12 CAH derivatives had phenyl or naphthyl groups with different substitution patterns on either side of the α,β-unsaturated ketone. Among them, 3f, which had a naphthaldehyde group, was the most potent at inhibiting PND in vitro, ex vivo, and in vivo. To assess their interactions with transient receptor potential cation channel subfamily A member 1 (TRPA1) as a target of CAH, molecular docking studies were performed. Hydrophobic interactions had the highest binding affinity. To evaluate the underlying pharmacological mechanism, we performed bioinformatics analysis of the effect of 3f on PND based on coding genes and miRNAs regulated by CAH, suggesting that 3f affects oxidative stress in Schwann cells. The results show 3f to be a potential lead compound for the development of novel synthetic drugs for the treatment of peripheral neurodegenerative diseases.

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Novel Cinnamaldehyde Derivatives Inhibit Peripheral Nerve Degeneration by Targeting Schwann Cells

Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus. Tight glycaemic management focused on lowering haemoglobin A1C and increasing time in the target glucose range along with metabolic risk factor management form the cornerstone of DPN prevention. However, there is limited evidence supporting the efficacy of glycaemic and metabolic control in reducing the symptoms and complications of DPN, including pain once painful DPN develops. DPN treatments include pharmacological agents and non-pharmacological interventions such as foot care and lifestyle modifications. Pharmacological agents primarily address pain symptoms, which affect 25–35% of people with DPN. First-line agents include the anticonvulsants pregabalin and gabapentin, the serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine, and secondary amine tricyclic antidepressants, including nortriptyline and desipramine. All agents have unique pharmacological, safety and clinical profiles, and agent selection should be guided by the presence of comorbidities, potential for adverse effects, drug interactions and costs. Even with the current treatment options, people are commonly prescribed less than the recommended dose of medications, leading to poor management of DPN symptoms and treatment discontinuation. By keeping up with the latest therapy algorithms and treatment options, healthcare professionals can improve the care for people with DPN.

Katherine M Mahoney

Papers

Diabetes: how to manage diabetic peripheral neuropathy