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Novel Therapeutic Strategies in Diabetes

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 540

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Session of Endocrinology and Metabolic Diseases, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Interests: diabetes mellitus; PRDX6; oxidative stress; metabolic syndrome
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Special Issue Information

Dear Colleagues,

Diabetes is a chronic metabolic disorder characterized by elevated blood glucose levels, which, if left untreated, can lead to severe complications such as cardiovascular disease, kidney failure, and neuropathy. In recent years, there have been significant advances in diabetes treatment due to a better understanding of the disease's pathophysiology and the development of innovative therapeutic strategies. This Special Issue aims to explore these new therapeutic strategies developed to treat both type 1 and type 2 diabetes more effectively.

One of the most promising research areas is the development of incretin-based therapies. Incretins, such as GLP-1 (glucagon-like peptide-1), are hormones that increase insulin secretion in response to meals. GLP-1 receptor agonists such as liraglutide and semaglutide are popular because they lower blood glucose levels, promote weight loss, and provide cardiovascular benefits. These drugs not only increase insulin secretion but also inhibit the release of glucagon, slow gastric emptying, and reduce appetite. The versatile effects of GLP-1 receptor agonists make them a valuable option for patients with type 2 diabetes, especially those struggling with obesity and cardiovascular risks.

Another novel approach is SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitors), which prevent glucose reabsorption in the kidneys, leading to glucose excretion in the urine. Drugs such as empagliflozin and dapagliflozin have shown significant benefits, including a reduced risk of heart failure and progression of kidney disease. These drugs are particularly promising for patients with type 2 diabetes who have cardiovascular or renal comorbidities, as they have a protective effect beyond lowering blood glucose levels.

The advent of immunotherapy has opened new doors in the treatment of type 1 diabetes. Unlike type 2 diabetes, which is primarily characterized by insulin resistance, type 1 diabetes results from an autoimmune attack on the beta cells of the pancreas. Recent advances in immunomodulatory therapies aim to preserve or restore beta cell function. For example, teplizumab, a monoclonal antibody against CD3, has shown the potential to delay the onset of type 1 diabetes in high-risk individuals by modulating the immune response directed against beta cells. Such therapies represent a paradigm shift in the treatment of type 1 diabetes, as they focus on halting the progression of the disease rather than just treating the symptoms.

Gene therapy also holds great promise, particularly for its potential to provide a long-term solution to diabetes management. Recent studies have investigated the possibility of modifying cells outside the pancreas to produce insulin or directly modifying the genes responsible for beta cell dysfunction. While these therapies are still experimental, they could offer a unique treatment that significantly reduces or eliminates the need for insulin therapy.

Another innovative development is artificial pancreas systems that combine continuous glucose monitoring (CGM) with automatic insulin delivery. These closed-loop systems use algorithms to predict glucose trends and adjust real-time insulin delivery. They better mimic the function of a healthy pancreas than conventional insulin pumps. The initial results of clinical studies are promising. They show better control of blood glucose levels and fewer hypoglycemic episodes than conventional insulin therapy.

In addition to these pharmacological and technological innovations, the focus in diabetes treatment is increasingly on personalized medicine. Genomics and metabolomics advances enable customized treatment plans based on an individual's genetic predisposition, lifestyle, and disease progression. Personalized approaches can help optimize the effectiveness of treatment, minimize side effects, and improve the overall quality of life of diabetics.

In summary, the new therapeutic strategies for diabetes significantly advance our ability to treat this complex and prevalent disease. From incretin-based therapies and SGLT2 inhibitors to immunotherapy, gene therapy, and artificial pancreas systems, these innovations offer new hope for patients. As research continues to evolve, even more effective and targeted treatments will likely emerge, potentially transforming diabetes care shortly.

Dr. Aikaterini Andreadi
Guest Editor

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Keywords

  • diabetes mellitus
  • type 1 and type 2 diabetes
  • GLP1-RA
  • SGLT2i
  • smart pen and CSII
  • micro and macrovascular complications
  • cardiovascular risk
  • diabetic foot

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Published Papers (2 papers)

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21 pages, 4619 KiB  
Article
Macrophage Depletion Alleviates Immunosenescence in Diabetic Kidney by Modulating GDF-15 and Klotho
by Asma S. Alonazi, Rana M. Aloraini, Lama M. Albulayhi, Layal M. Alshehri, Anfal F. Bin Dayel, Maha A. Alamin, Nouf T. Aldamri, Tahani K. Alshammari, Dalal A. Alkhelb, Wedad S. Sarawi, Hanan K. Alghibiwi, Nawal M. Alrasheed, Doaa M. Elnagar and Nouf M. Alrasheed
Int. J. Mol. Sci. 2025, 26(9), 3990; https://doi.org/10.3390/ijms26093990 - 23 Apr 2025
Viewed by 130
Abstract
Cellular senescence is a hallmark of aging and contributes to age-related diseases, including diabetic nephropathy (DN). Additionally, macrophage-mediated inflammation has been linked with DKD. Therefore, we investigated the effect of macrophage depletion on kidney cell senescence in DN, focusing on the relationship between [...] Read more.
Cellular senescence is a hallmark of aging and contributes to age-related diseases, including diabetic nephropathy (DN). Additionally, macrophage-mediated inflammation has been linked with DKD. Therefore, we investigated the effect of macrophage depletion on kidney cell senescence in DN, focusing on the relationship between the GDF-15 and Klotho signaling pathways. Wistar albino rats (n = 24) were divided into four groups: healthy control, liposomal clodronate (LC)-treated healthy, diabetic, and LC-treated diabetic groups. Rats in the LC-treated healthy, diabetic, and LC-treated diabetic groups were intravenously administered LC once a week for 4 weeks. Rat models of type 2 diabetes were successfully established via the administration of streptozotocin and a high-fat diet, as evidenced by increased blood glucose levels, kidney weight to body weight (KW/BW) ratio, serum albumin, creatinine, and urea levels, kidney damage, and oxidative stress. However, LC-mediated macrophage depletion reduced the KW/BW ratio, improved serum and oxidative parameters, decreased inflammatory markers (IL-6 and TNF-α), and ameliorated oxidative stress. Additionally, LC treatment promoted macrophage polarization towards the anti-inflammatory phenotype, downregulated GDF-15 expression, upregulated Klotho expression, and ameliorated kidney damage. In conclusion, macrophage depletion combats kidney senescence by modulating Klotho and GDF-15, indicating their potential as novel targets in DN treatment. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies in Diabetes)
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16 pages, 4823 KiB  
Article
Systematic Inflammation and Oxidative Stress Elevation in Diabetic Retinopathy and Diabetic Patients with Macular Edema
by Kamelia Petkova-Parlapanska, Valeria Draganova, Ekaterina Georgieva, Petya Goycheva, Galina Nikolova and Yanka Karamalakova
Int. J. Mol. Sci. 2025, 26(8), 3810; https://doi.org/10.3390/ijms26083810 - 17 Apr 2025
Viewed by 202
Abstract
This study investigates the association between diabetic retinopathy (DR) and its complication, diabetic macular edema (DME), and compared it with biomarkers of oxidative stress. This study aimed to compare the main indicators of the development of diabetic retinopathy measured as parameters of oxidative [...] Read more.
This study investigates the association between diabetic retinopathy (DR) and its complication, diabetic macular edema (DME), and compared it with biomarkers of oxidative stress. This study aimed to compare the main indicators of the development of diabetic retinopathy measured as parameters of oxidative stress and compared to lipid oxidation, DNA damage, and cytokine levels and to monitor their quantitative manifestation in DME. This study evaluated 134 patients (62 males and 72 females; aged 62.10 ± 11.22 years) and divided them into two groups: type 2 diabetes mellitus with DR and type 2 diabetes mellitus with DME. All results were compared with healthy volunteers (n = 94) and showed that patients with DME had significantly higher levels of ROS, cytokine production, lipid oxidation, and DNA damage. In addition, patients with DME had decreased levels of nitric oxide (NO) and an impaired NO synthase (NOS) system (p < 0.05). These findings suggest that patients with DR and DME are unable to compensate for high levels of oxidative stress. Reduced NO levels in patients with DME may be due to impaired NO availability. This study highlights compromised oxidative status as a contributing factor to DME in patients with decompensated type 2 diabetes mellitus. An assessment of oxidative stress levels and inflammatory biomarkers may aid in the early detection and prediction of diabetic complications. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies in Diabetes)
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