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New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications, 2nd...
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New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications, 2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 9513

Special Issue Editors

Dr. Ana Maria Dascalu

E-Mail Website
Guest Editor
Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania
Interests: diabetic retinopathy; glaucoma; age related macular degeneration; optic neuropathies; inflammatory biomarkers
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Dragos Serban

E-Mail Website
Guest Editor
Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania
Interests: laparoscopic surgery; inflammatory biomarkers; emergency surgery; colorectal cancer; diabetic foot
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diabetes mellitus is a major health problem globally, with an ascendant trend expected to reach up to 700 million cases by 2045. The microvascular triad includes diabetic retinopathy, nephropathy, and neuropathy, unique in diabetes. Despite significant achievements in early diagnosis and therapy, diabetic retinopathy remains the leading cause of blindness in the working-age population, with a severe impact on patients' quality of life. Diabetic peripheral neuropathy affects nearly 50% of adults with diabetes during their lifetime, and it represents a major risk factor for diabetic foot ulcer (DFU), the most common cause of non-traumatic amputations worldwide. Classically, the duration of diabetes, level of hyperglycemia, arterial hypertension, and dyslipidemia are the most incriminated risk factors. Novel research has found multiple molecular pathways that may interfere with vascular dysfunction, ischemia, and tissular damage.

In this Special Issue, we welcome original articles and reviews providing new research data on diabetic microvascular complications: novel biomarkers, early diagnosis, pathology, molecular mechanisms, and new therapies in diabetic retinopathy, nephropathy, neuropathy, and diabetic foot ulcers.

Dr. Ana Dascalu
Prof. Dr. Dragos Serban
Guest Editors

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Keywords

  • diabetic retinopathy
  • diabetic foot ulcer
  • inflammatory biomarkers
  • microbiota
  • novel therapies

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Published Papers (6 papers)

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Research

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13 pages, 2939 KiB  
Article
Predictive Vascular Changes in OCTA in Diabetic Patients
by Jelena Cuk, Dejana Stanisavljevic, Jelena Vasilijevic, Milica Jeremic Kaplarevic, Milica Micovic, Aleksandar Risimic and Dijana Risimic
Biomedicines 2025, 13(6), 1486; https://doi.org/10.3390/biomedicines13061486 - 17 Jun 2025
Viewed by 253
Abstract
Background/Objectives: The aim of this study was to investigate quantitative differences in optical coherence tomography angiography (OCTA) between diabetic patients and healthy controls and to identify the early OCTA biomarkers for diabetic macular changes. Methods: Ophthalmological examination and OCTA were performed [...] Read more.
Background/Objectives: The aim of this study was to investigate quantitative differences in optical coherence tomography angiography (OCTA) between diabetic patients and healthy controls and to identify the early OCTA biomarkers for diabetic macular changes. Methods: Ophthalmological examination and OCTA were performed on two groups of diabetic patients (with and without mild diabetic retinopathy) and healthy controls. Macular, foveal, perifoveal, and parafoveal vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), foveal avascular zone (FAZ), and flow area in the choriocapillaris were calculated. Results: A total of 431 eyes of 233 participants were analyzed. The VD in the SCP in the whole macula was the lowest in the DM + DR group and lower than in the DMnoDR group; however, in the fovea, it was the highest in the DM + DR group and higher than in the DMnoDR group. The VD in the SCP in the parafovea was lower in the DM + DR group than in the DMnoDR group, and in the perifovea, it was lower in the DMnoDR group than in the control group. The VD in the DCP in the macula, parafovea, and perifovea was lower in the DM + DR group than in the DMnoDR and control groups. The FAZ and flow areas in the choriocapillaris were smaller in the DM + DR group than in both the DMnoDR and control groups. Conclusions: VD reduction in the SCP and the DCP of the macular and parafoveal regions, as well as in the DCP of the perifoveal region, may indicate progression of diabetic retinopathy from subclinical to clinical stages; however, an increase in the foveal region in the SCP can be a compensatory mechanism. VD reduction in the perifovea and whole macula in the SCP can be a screening factor for subclinical macular changes. FAZ reduction before clinical signs of retinopathy may be an early compensatory vascular mechanism. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications, 2nd Edition)
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18 pages, 3200 KiB  
Article
Predictive Role of Complete Blood Count-Derived Inflammation Indices and Optical Coherence Tomography Biomarkers for Early Response to Intravitreal Anti-VEGF in Diabetic Macular Edema
by Ece Ergin, Ana Maria Dascalu, Daniela Stana, Laura Carina Tribus, Andreea Letitia Arsene, Marina Ionela Nedea, Dragos Serban, Claudiu Eduard Nistor, Corneliu Tudor, Dan Dumitrescu, Paul Lorin Stoica and Bogdan Mihai Cristea
Biomedicines 2025, 13(6), 1308; https://doi.org/10.3390/biomedicines13061308 - 27 May 2025
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Abstract
Background: Diabetic macular edema (DME) is the leading cause of vision impairment in diabetic patients, with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections being the first-line therapy. However, one-third of patients exhibit persistent DME despite treatment, suggesting additional pathogenic factors. This study aimed [...] Read more.
Background: Diabetic macular edema (DME) is the leading cause of vision impairment in diabetic patients, with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections being the first-line therapy. However, one-third of patients exhibit persistent DME despite treatment, suggesting additional pathogenic factors. This study aimed to evaluate the predictive value of complete blood count (CBC)-based inflammation indexes and optical coherence tomography (OCT) parameters in determining early anti-VEGF treatment effectiveness in DME. Methods: One hundred and four naïve patients with DME, treated with 0.05 mL of intravitreal aflibercept were retrospectively analyzed. Blood parameters analyzed included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Baseline OCT biomarkers included subretinal fluid (SRF), intraretinal cysts (IRC), hyperreflective retinal spots (HRS), and disorganization of retinal inner layers (DRIL). Treatment response was defined as a minimum 10% reduction in central macular thickness (CMT) at one month post-injection. Results: NLR, MLR, PLR, and SII were significantly higher in non-responders (p < 0.001), but their predictive value was fair, with an area under the ROC curve ranging between 0.704 (MLR) and 0.788 (SII). A multivariate model including SII, initial CMT, and the presence of IRC showed an excellent prediction value for early anatomical response (AUC ROC of 0.911). At the same time, lower PLR, DRIL, SRF, and the absence of HRF were correlated with early gain in BCVA. Conclusions: CBC-derived inflammation indices and OCT biomarkers have prognostic value in predicting early response to anti-VEGF therapy in DME in terms of functional and anatomical outcomes. These findings could help identify poor responders and guide personalized treatment strategies. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications, 2nd Edition)
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19 pages, 2475 KiB  
Article
Impact of Subthreshold Micropulse Laser on the Vascular Network in Diabetic Macular Edema: An Optical Coherence Tomography Angiography Study
by Barbara Sabal, Edward Wylęgała and Sławomir Teper
Biomedicines 2025, 13(5), 1194; https://doi.org/10.3390/biomedicines13051194 - 14 May 2025
Viewed by 390
Abstract
Objectives: To evaluate the short- and long-term effects of subthreshold micropulse laser (SMPL) treatment on the microvascular network in diabetic macular edema (DME). Methods: This 12-month prospective study included 67 eyes (67 patients) with mild DME and good best-corrected visual acuity [...] Read more.
Objectives: To evaluate the short- and long-term effects of subthreshold micropulse laser (SMPL) treatment on the microvascular network in diabetic macular edema (DME). Methods: This 12-month prospective study included 67 eyes (67 patients) with mild DME and good best-corrected visual acuity (BCVA), randomized into SMPL (33 eyes) or sham (34 eyes) groups. Assessments were performed at baseline (T1), 3 months (T2), and 12 months (T3). Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to measure central retinal thickness (CRT), macular thickness (MT), macular volume (MV), foveal avascular zone (FAZ) area, microaneurysm (MA) count, and vessel parameters in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Results: The SMPL group showed a greater relative reduction in FAZ area in the SCP at 3 months (3.21 ± 13.03% vs. −5.73 ± 13.3%; p = 0.032) with a trend toward significance at 12 months (2.37 ± 12.47% vs. −3.3 ± 7.92%; p = 0.086) compared to the sham group. No changes in FAZ size, MA count, and other microvascular parameters were observed in either group. In the SMPL group, BCVA improved at 3 months (T2 > T1, p = 0.003); CRT decreased at 12 months (T2 > T3, p = 0.023); MT decreased at 12 months (T2 > T3, p = 0.006) and MV decreased at 12 months (T2 > T3, p = 0.007). No changes were detected in the sham group. No treatment-related complications occurred. Conclusions: SMPL may improve the macular microvasculature in mild DME by reducing FAZ size in the SCP. It provides visual and functional benefits while maintaining a favorable safety profile. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications, 2nd Edition)
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11 pages, 1787 KiB  
Article
Comparison of Vascular Density Changes After Cataract Surgery in Diabetic Patients with and Without Pseudoexfoliation Syndrome Using Optical Coherence Tomography Angiography
by Lelde Svjascenkova, Arturs Zemitis, Janis Gredzens and Guna Laganovska
Biomedicines 2025, 13(4), 908; https://doi.org/10.3390/biomedicines13040908 - 8 Apr 2025
Viewed by 415
Abstract
Background: This study aims to evaluate changes in the central retina in patients with type 2 diabetes mellitus (T2DM) undergoing uncomplicated small incision cataract surgery with or without pseudoexfoliation syndrome (PEXS) using optical coherence tomography angiography (OCTA). Methods: In this prospective, longitudinal study, [...] Read more.
Background: This study aims to evaluate changes in the central retina in patients with type 2 diabetes mellitus (T2DM) undergoing uncomplicated small incision cataract surgery with or without pseudoexfoliation syndrome (PEXS) using optical coherence tomography angiography (OCTA). Methods: In this prospective, longitudinal study, 67 T2DM patients underwent cataract surgery. Twelve of them had PEXS. All parameters were measured at two time points. Macular 3 × 3 mm and 6 × 6 mm OCTA images were obtained. All data were analyzed using R statistical software (version 4.4.1). Results: Parafoveal vascular density (VD) in the superior capillary plexus and the deep capillary plexus increased in the non-PEX group. There was an increase in VD in perifoveal vascular density in the deep capillary plexus in both groups. Three months after cataract surgery, changes in perifoveal vascular density in the deep capillary plexus increased in both groups and were significant. Conclusion: Perifoveal vascular density in the deep capillary plexus showed a significant increase in VD, regardless of the presence of PEXS. Parafoveal VD in the deep and superficial capillary plexuses appeared to be sensitive primarily in non-PEXS patients, with a notable increase observed in these areas three months after surgery. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications, 2nd Edition)
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Review

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17 pages, 1564 KiB  
Review
Diabetic Foot Ulcers: Pathophysiology, Immune Dysregulation, and Emerging Therapeutic Strategies
by John Dawi, Kevin Tumanyan, Kirakos Tomas, Yura Misakyan, Areg Gargaloyan, Edgar Gonzalez, Mary Hammi, Serly Tomas and Vishwanath Venketaraman
Biomedicines 2025, 13(5), 1076; https://doi.org/10.3390/biomedicines13051076 - 29 Apr 2025
Cited by 1 | Viewed by 1866
Abstract
Diabetic foot ulcers (DFUs) are among the most common and debilitating complications of diabetes mellitus (DM), affecting approximately 15–25% of patients and contributing to over 85% of non-traumatic amputations. DFUs impose a substantial clinical and economic burden due to high recurrence rates, prolonged [...] Read more.
Diabetic foot ulcers (DFUs) are among the most common and debilitating complications of diabetes mellitus (DM), affecting approximately 15–25% of patients and contributing to over 85% of non-traumatic amputations. DFUs impose a substantial clinical and economic burden due to high recurrence rates, prolonged wound care, and frequent hospitalizations, accounting for billions in healthcare costs worldwide. The multifactorial pathophysiology of DFUs involves peripheral neuropathy, peripheral arterial disease, chronic inflammation, and impaired tissue regeneration. Recent studies underscore the importance of immune dysregulation—specifically macrophage polarization imbalance, regulatory T cell dysfunction, and neutrophil impairment—as central mechanisms in wound chronicity. These immune disruptions sustain a pro-inflammatory environment dominated by cytokines, such as TNF-α, IL-1β, and IL-6, which impair angiogenesis and delay repair. This review provides an updated synthesis of DFU pathogenesis, emphasizing immune dysfunction and its therapeutic implications. We examine emerging strategies in immunomodulation, regenerative medicine, and AI-based wound technologies, including SGLT2 inhibitors, biologics, stem cell therapies, and smart dressing systems. These approaches hold promise for accelerating healing, reducing amputation risk, and personalizing future DFU care. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications, 2nd Edition)
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25 pages, 1237 KiB  
Review
Management of Microcomplications of Diabetes Mellitus: Challenges, Current Trends, and Future Perspectives in Treatment
by Hande Yapislar and Esra Bihter Gurler
Biomedicines 2024, 12(9), 1958; https://doi.org/10.3390/biomedicines12091958 - 28 Aug 2024
Cited by 8 | Viewed by 5453
Abstract
Diabetes mellitus is a chronic metabolic disorder characterized by high blood sugar levels, which can lead to severe health issues if not managed effectively. Recent statistics indicate a significant global impact, with 463 million adults diagnosed worldwide and this projected to rise to [...] Read more.
Diabetes mellitus is a chronic metabolic disorder characterized by high blood sugar levels, which can lead to severe health issues if not managed effectively. Recent statistics indicate a significant global impact, with 463 million adults diagnosed worldwide and this projected to rise to 700 million by 2045. Type 1 diabetes is an autoimmune disorder where the immune system attacks pancreatic beta cells, reducing insulin production. Type 2 diabetes is primarily due to insulin resistance. Both types of diabetes are linked to severe microvascular and macrovascular complications if unmanaged. Microvascular complications, such as diabetic retinopathy, nephropathy, and neuropathy, result from damage to small blood vessels and can lead to organ and tissue dysfunction. Chronic hyperglycemia plays a central role in the onset of these complications, with prolonged high blood sugar levels causing extensive vascular damage. The emerging treatments and current research focus on various aspects, from insulin resistance to the intricate cellular damage induced by glucose toxicity. Understanding and intervening in these pathways are critical for developing effective treatments and managing diabetes long term. Furthermore, ongoing health initiatives, such as increasing awareness, encouraging early detection, and improving treatments, are in place to manage diabetes globally and mitigate its impact on health and society. These initiatives are a testament to the collective effort to combat this global health challenge. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications, 2nd Edition)
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