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Pathological evaluation of the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy.Pathology International Jun 2024Currently, there are more than 10 million patients with diabetes mellitus in Japan. Therefore, the need to explore the pathogenesis of diabetes and the complications... (Review)
Review
Currently, there are more than 10 million patients with diabetes mellitus in Japan. Therefore, the need to explore the pathogenesis of diabetes and the complications leading to its cure is becoming increasingly urgent. Pathological examination of pancreatic tissues from patients with type 2 diabetes reveals a decrease in the volume of beta cells because of a combination of various stresses. In human type 2 diabetes, islet amyloid deposition is a unique pathological change characterized by proinflammatory macrophage (M1) infiltration into the islets. The pathological changes in the pancreas with islet amyloid were different according to clinical factors, which suggests that type 2 diabetes can be further subclassified based on islet pathology. On the other hand, diabetic peripheral neuropathy is the most frequent diabetic complication. In early diabetic peripheral neuropathy, M1 infiltration in the sciatic nerve evokes oxidative stress or attenuates retrograde axonal transport, as clearly demonstrated by in vitro live imaging. Furthermore, islet parasympathetic nerve density and beta cell volume were inversely correlated in type 2 diabetic Goto-Kakizaki rats, suggesting that diabetic peripheral neuropathy itself may contribute to the decrease in beta cell volume. These findings suggest that the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy may be interrelated.
PubMed: 38888200
DOI: 10.1111/pin.13458 -
Khirurgiia 2024To evaluate prognostic significance of tissue oximetry in healing of trophic defects in patients with diabetic foot syndrome (DFS) after endovascular revascularization.
OBJECTIVE
To evaluate prognostic significance of tissue oximetry in healing of trophic defects in patients with diabetic foot syndrome (DFS) after endovascular revascularization.
MATERIAL AND METHODS
In 42 patients with DFS, tissue oximetry was performed in angiosome projection with the FORE-SIGHT MC-2000 (CASMED) device before and the next day after revascularization of lower limb arteries. The 1st group included 30 patients with wound healing throughout 3 months, the 2nd group included 12 patients with amputation or no healing of trophic defects.
RESULTS
Direct revascularization was more common in the 1st group (=0.001). On the day after intervention, oxygen saturation (StO) increased in all angiosomes in both groups (<0.05). StO increment differed significantly between groups in all angiosomes except for point I (<0.05). According to ROC analysis, StO increment by 4.5% in absolute values and 7.9% in percentage leads to trophic defect healing within 3 months (sensitivity and specificity were 76.7% and 66.7% for absolute values, 80% and 58.3% for percentage, respectively).
CONCLUSION
Evaluation of StO in target angiosome may be valuable to predict trophic defect healing after endovascular surgery.
Topics: Humans; Diabetic Foot; Male; Female; Middle Aged; Oximetry; Wound Healing; Aged; Endovascular Procedures; Prognosis; Oxygen Saturation; Treatment Outcome; Spectroscopy, Near-Infrared; Lower Extremity
PubMed: 38888015
DOI: 10.17116/hirurgia202406120 -
Physiotherapy Research International :... Jul 2024Diabetic peripheral neuropathy (DPN) occurs in >50% of diabetic patients and is a high risk-factor of balance problems and risk of falls. Impaired balance can lead to... (Randomized Controlled Trial)
Randomized Controlled Trial
Combined effects of strength and balance training versus aerobic training on balance, neuropathy symptoms and quality of life in patients with diabetic peripheral neuropathy.
BACKGROUND
Diabetic peripheral neuropathy (DPN) occurs in >50% of diabetic patients and is a high risk-factor of balance problems and risk of falls. Impaired balance can lead to reduced function, which has a detrimental effect on patients' quality of life. Structured strength and balance training can result in sustained improvements in muscle strength, coordination, balance, functional status and quality of life.
OBJECTIVE
To determine the combined effects of strength and balance training versus aerobic training on balance, severity of symptoms of DPN, and quality of life in patients with DPN.
METHODS
This double blinded, two arm parallel design Randomized Clinical Trial. The study was conducted from March to December 2020 in the AIMS diabetic center Peshawar, Pakistan. Participants were selected through convenience sampling technique and randomly allocated into strength plus balance and aerobic training groups. Type 2 diabetic patients of both sexes, aged 40 to 80 years, with a Toronto neuropathy score ≥6 recruited, while patients with ulceration/infection of feet, medical/Surgical conditions, and non-ambulatory patients were excluded from this study. Intervention was applied 3 days a week for 8 weeks. The Toronto clinical neuropathy system was used to assess neuropathy severity, SF-36 to assess quality of life and the Berg balance scale was used for assessment of balance. Assessment was done at the baseline and after 8 weeks of intervention using SPSS. Version 22 was used for analysis.
RESULTS
The mean age of the participants was 60.80 ± 9.73. Between group analysis, which showed were statistically insignificant for neuropathy severity, balance and all domains of quality of life (p-value >0.05) except SF-36 General Health Perception Score, with Mean ± SD of 62.50 ± 7.54 in group A versus Mean ± SD of in group B 60.00 ± 15.98 (p-value = 0.05). Within group analysis showed statistically significant results for neuropathy severity, balance and all domains of quality of life (p-value<0.05).
CONCLUSION
This study concluded that there is a statistically significant effect of structured balance and strength training and aerobic training on severity of DPN, balance and quality of life. But there was no statistically significant difference in improvement between the two intervention groups.
Topics: Humans; Quality of Life; Male; Postural Balance; Diabetic Neuropathies; Female; Middle Aged; Aged; Resistance Training; Double-Blind Method; Adult; Diabetes Mellitus, Type 2; Aged, 80 and over; Exercise; Exercise Therapy; Pakistan; Muscle Strength
PubMed: 38887171
DOI: 10.1002/pri.2103 -
PloS One 2024This study aimed to develop a novel Gelatin silver oxide material for releasing nitric oxide bionanocomposite wound dressing with enhanced mechanical, chemical, and...
This study aimed to develop a novel Gelatin silver oxide material for releasing nitric oxide bionanocomposite wound dressing with enhanced mechanical, chemical, and antibacterial properties for the treatment of diabetic wounds. The gelatin- silver oxide nanoparticles (Ag2O-NP) bio nanocomposite was prepared using chitosan and gelatin polymers incorporated with silver oxide nanoparticles through the freeze-drying method. The samples were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. Results showed that the Ag2O-NP nanoparticles increased porosity, decreased pore size, and improved elastic modulus. The Ag2O-NP wound dressing exhibited the most effective antibacterial properties against Staphylococcus aureus and Escherichia coli. Among the samples, the wound dressing containing silver oxide nanoparticles demonstrated superior physical and mechanical properties, with 48% porosity, a tensile strength of 3.2 MPa, and an elastic modulus of 51.7 MPa. The fabricated wound dressings had a volume ratio of empty space to total volume ranging from 40% to 60%. In parallel, considering the complications of diabetes and its impact on the vascular system, another aspect of the research focused on developing a per2mediated wound dressing capable of releasing nitric oxide gas to regenerate damaged vessels and accelerate diabetic wound healing. Chitosan, a biocompatible and biodegradable polymer, was selected as the substrate for the wound dressing, and beta-glycerophosphate (GPβ), tripolyphosphate (TPP), and per2mediated alginate (AL) were used as crosslinkers. The chitosan-alginate (CS-AL) wound dressing exhibited optimal characteristics in terms of hole count and uniformity in the scanning electron microscope test. It also demonstrated superior water absorption (3854%) and minimal air permeability. Furthermore, the CS-AL sample exhibited an 80% degradation rate after 14 days, indicating its suitability as a wound dressing. The wound dressing was loaded with S-nitrosoglutathione (GSNO) powder, and the successful release of nitric oxide gas was confirmed through the grease test, showing a peak at a wavelength of 540 nm. Subsequent investigations revealed that the treatment of human umbilical vein endothelial cells (HUVECs) with high glucose led to a decrease in the expression of PER2 and SIRT1, while the expression of PER2 increased, which may subsequently enhance the expression of SIRT1 and promote cell proliferation activity. However, upon treatment of the cells with the modified materials, an increase in the expression of PER2 and SIRT1 was observed, resulting in a partial restoration of cell proliferative activity. This comprehensive study successfully developed per2-mediated bio-nanocomposite wound dressings with improved physical, mechanical, chemical, and antibacterial properties. The incorporation of silver oxide nanoparticles enhanced the antimicrobial activity, while the released nitric oxide gas from the dressing demonstrated the ability to mitigate vascular endothelial cell damage induced by high glucose levels. These advancements show promising potential for facilitating the healing process of diabetic wounds by addressing complications associated with diabetes and enhancing overall wound healing.
Topics: Gelatin; Wound Healing; Nitric Oxide; Bandages; Silver Compounds; Humans; Escherichia coli; Anti-Bacterial Agents; Staphylococcus aureus; Chitosan; Metal Nanoparticles; Porosity; Diabetic Foot; Nanoparticles; Oxides
PubMed: 38885218
DOI: 10.1371/journal.pone.0298124 -
Journal of Foot and Ankle Research Jun 2024Diabetic foot ulcers (DFUs) are commonly contaminated with pathogenic organisms and precede most diabetes-related amputations. Antimicrobial dressings are used in the...
INTRODUCTION
Diabetic foot ulcers (DFUs) are commonly contaminated with pathogenic organisms and precede most diabetes-related amputations. Antimicrobial dressings are used in the treatment of DFUs; however, recent guidelines do not support their use. There are no data describing the experience of antimicrobial dressing use among podiatrists in Aotearoa New Zealand (AoNZ). This study aimed to (i) determine which antimicrobial dressings podiatrists in AoNZ use for the management of diabetic foot ulcers; and (ii) determine what factors influence AoNZ podiatrists' use of antimicrobial dressing when managing DFUs.
METHODS
An anonymous cross-sectional web-based survey was undertaken. Participants were AoNZ registered podiatrists who managed DFUs in their practice. The survey included questions relating to personal and professional demographic characteristics and DFU management and dressing practices. Descriptive statistics were computed to address the research aims.
RESULTS
Responses from 43 AoNZ podiatrists were included. Participants reported both cadexomer iodine and silver dressings were the most common antimicrobial dressings used, with honey dressings being the least frequently used. The most influential factors in choosing antimicrobial dressings when managing DFUs were the presence of current infection, ulcer exudate and ability to prevent future infection. The least influential factors in choosing antimicrobial dressings when managing DFUs were patient preferences, cost of dressings and comfort of dressing/pain on removal.
CONCLUSIONS
AoNZ podiatrists managing DFUs primarily use antimicrobial dressings containing cadexomer iodine or silver as active ingredients, while lower-cost options, such as honey and povidone iodine are less often used. Current recommendations highlight the lack of evidence to support positive outcomes from any particular antimicrobial dressing over another and advocate that exudate control, comfort and cost be prioritised in decision-making. As cost has been an increasing burden to our healthcare funding, clinicians and organisations may consider this before purchasing and stocking expensive dressings.
Topics: Humans; Diabetic Foot; New Zealand; Cross-Sectional Studies; Bandages; Podiatry; Male; Female; Practice Patterns, Physicians'; Middle Aged; Anti-Infective Agents; Surveys and Questionnaires; Adult; Honey
PubMed: 38884388
DOI: 10.1002/jfa2.12032 -
Critical Reviews in Biomedical... 2024Chronic wounds can be classified as diabetic foot ulcers, pressure ulcers, or venous leg ulcers. Chronic wound management has become a threat to clinicians and... (Review)
Review
Chronic wounds can be classified as diabetic foot ulcers, pressure ulcers, or venous leg ulcers. Chronic wound management has become a threat to clinicians and constitutes a major healthcare burden. The healing process of chronic wounds requires many factors to work in concert to achieve optimal healing. Various treatment options, ranging from hypoxia to infection, have evolved considerably to address the challenges associated with chronic wound healing. The conventional and accelerating treatments for chronic wounds still represent an unmet medical need due to the complex pathophysiology of the chronic wound microenvironment. In clinical settings, traditional chronic wound care practices rely on nonspecific topical treatment, which can reduce pain and alleviate disease progression with varying levels of success but fail to completely cure the wounds. Conventional wound dressings, such as hydrocolloids, gauze, foams, and films, have also shown limited success for the treatment of chronic wounds and only act as a physical barrier and absorb wound exudates. Emerging advances in treatment approaches, including novel therapies (stem cells, microRNAs, and nanocarrier-based delivery systems) and multifunctional biological dressings, have been reported for chronic wound repair. This review summarizes the challenges offered by chronic wounds and discusses recent advancements in chronic wound treatment.
Topics: Humans; Wound Healing; Biological Dressings; Chronic Disease; Animals; Bandages; Diabetic Foot; Wounds and Injuries
PubMed: 38884212
DOI: 10.1615/CritRevBiomedEng.2024053066 -
International Journal of Nanomedicine 2024Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is...
INTRODUCTION
Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is attributed to multiple factors, including hyperglycemia, neuropathy, chronic inflammation, oxidative damage, and decreased vascularization.
RATIONALE
To address these challenges, this project aims to develop bioactive, fast-dissolving nanofiber dressings composed of polyvinylpyrrolidone loaded with a combination of an antibiotic (moxifloxacin or fusidic acid) and anti-inflammatory drug (pirfenidone) using electrospinning technique to prevent the bacterial growth, reduce inflammation, and expedite wound healing in diabetic wounds.
RESULTS
The fabricated drug-loaded fibers exhibited diameters of 443 ± 67 nm for moxifloxacin/pirfenidone nanofibers and 488 ± 92 nm for fusidic acid/pirfenidone nanofibers. The encapsulation efficiency, drug loading and drug release studies for the moxifloxacin/pirfenidone nanofibers were found to be 70 ± 3% and 20 ± 1 µg/mg, respectively, for moxifloxacin, and 96 ± 6% and 28 ± 2 µg/mg, respectively, for pirfenidone, with a complete release of both drugs within 24 hours, whereas the fusidic acid/pirfenidone nanofibers were found to be 95 ± 6% and 28 ± 2 µg/mg, respectively, for fusidic acid and 102 ± 5% and 30 ± 2 µg/mg, respectively, for pirfenidone, with a release rate of 66% for fusidic acid and 80%, for pirfenidone after 24 hours. The efficacy of the prepared nanofiber formulations in accelerating wound healing was evaluated using an induced diabetic rat model. All tested formulations showed an earlier complete closure of the wound compared to the controls, which was also supported by the histopathological assessment. Notably, the combination of fusidic acid and pirfenidone nanofibers demonstrated wound healing acceleration on day 8, earlier than all tested groups.
CONCLUSION
These findings highlight the potential of the drug-loaded nanofibrous system as a promising medicated wound dressing for diabetic foot applications.
Topics: Diabetic Foot; Nanofibers; Animals; Moxifloxacin; Wound Healing; Bandages; Anti-Bacterial Agents; Pyridones; Fusidic Acid; Drug Liberation; Rats; Male; Diabetes Mellitus, Experimental; Povidone; Rats, Sprague-Dawley
PubMed: 38882541
DOI: 10.2147/IJN.S460467 -
Frontiers in Chemistry 2024As inhibitors of advanced glycation end products (AGEs), such as pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with...
As inhibitors of advanced glycation end products (AGEs), such as pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of aging, age-related diseases, and lifestyle-related diseases, including diabetic complications. In the present study, the MeOH extract of (EH; aerial parts of spp.) was found to inhibit the formation of -(carboxymethyl)lysine (CML) and -(carboxymethyl) arginine (CMA) during the incubation of collagen-derived gelatin with ribose. EH was purchased from Uchida Wakan-yaku Co., and a MeOH extract was prepared. Several steps of column chromatography purified the extract. Each fraction was tested for inhibitory activity by ELISA using monoclonal antibodies for CML and CMA. After activity-guided fractionation and purification by column chromatography, three new prenylflavonoids [named Koreanoside L (), Koreanoside E1 (), and Koreanoside E2 ()] and 40 known compounds (-) were isolated from EH, and their inhibitory effects against CML and CMA formation were tested. Among these, epimedokoreanin B (), epimedonin E (), epicornunin B (), and epicornunin F () inhibited the formation of both CML and CMA, with epimedokoreanin B () having the most potent inhibitory effect among the isolated compounds. To obtain the structure-activity relationships of , the phenolic hydroxy groups of were methylated by trimethylsilyl-diazomethane to afford the partially and completely methylated compounds of . Prenyl derivatives of propolis (artepillin C, baccharin, and drupanin) were used in the assay. As only showed significant activity among these compounds, the catechol group of the B ring and the two prenyl groups attached to the flavanone skeleton were essential for activity. These data suggest that could prevent the clinical complications of diabetes and age-related diseases by inhibiting AGEs.
PubMed: 38882216
DOI: 10.3389/fchem.2024.1407934 -
The Journal of the Association of... May 2024Diabetes mellitus (DM) is a common metabolic disorder that has been defined by hyperglycemia. Diabetic patients usually have high levels of oxidative stress....
INTRODUCTION
Diabetes mellitus (DM) is a common metabolic disorder that has been defined by hyperglycemia. Diabetic patients usually have high levels of oxidative stress. Mitochondrial dysfunction and inflammation of blood vessels are associated with a greater need for micronutrients in diabetic patients. These micronutrients may have an association with the complications in diabetics. The purpose of this study was to show the association of diabetic peripheral neuropathy (DPN) with levels of micronutrients such as copper (Cu), zinc (Zn), magnesium (Mg), and vitamin B (Vit B).
MATERIALS AND METHODS
This cross-sectional study was conducted in the Department of Medicine, Lala Lajpat Rai Memorial Medical College, Meerut. A total of 130 randomly selected cases of confirmed type-2 diabetic patients were included in this study. DPN cases were identified using the Michigan neuropathy screening instrument. Out of 130 diabetic patients, 28 patients were found to have diabetic neuropathy. The level of various micronutrients was assessed and correlated with the development of DPN.
RESULTS
The association of DPN with Zn (p-value of 0.02) and Vit B12 (p-value of 0.008) was found to be significant, whereas Cu (p-value of 0.57) and Mg (p-value of 0.24) were found to be insignificant.
Topics: Humans; Diabetic Neuropathies; Cross-Sectional Studies; Micronutrients; Middle Aged; Male; Female; Zinc; Copper; Diabetes Mellitus, Type 2; Magnesium; Vitamin B 12; Aged; Adult
PubMed: 38881112
DOI: 10.59556/japi.72.0493 -
The Journal of Biological Chemistry Jun 2024Glucoselysine (GL) is a unique advanced glycation end-product derived from fructose. The main source of fructose in vivo is the polyol pathway, and an increase in its...
Glucoselysine (GL) is a unique advanced glycation end-product derived from fructose. The main source of fructose in vivo is the polyol pathway, and an increase in its activity leads to diabetic complications. Here, we aimed to demonstrate that GL can serve as an indicator of the polyol pathway activity. Additionally, we propose a novel approach for detecting GL in peripheral blood samples using LC-MS/MS and evaluate its clinical usefulness. We successfully circumvent interference from fructoselysine, which shares the same molecular weight as GL, by performing ultrafiltration and hydrolysis without reduction, successfully generating adequate peaks for quantification in serum. Furthermore, using immortalized aldose reductase knockout mouse Schwann cells, we demonstrate that GL reflects the downstream activity of the polyol pathway and that GL produced intracellularly is released into the extracellular space. Clinical studies reveal that GL levels in patients with type 2 diabetes are significantly higher than those in healthy participants, while N-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1) levels are significantly lower. Both GL and MG-H1 show higher values among patients with vascular complications; however, GL varies more markedly than MG-H1 as well as hemoglobin A1c, fasting plasma glucose, and estimated glomerular filtration rate. Furthermore, GL remains consistently stable under various existing drug treatments for type 2 diabetes, whereas MG-H1 is impacted. To the best of our knowledge, we provide important insights in predicting diabetic complications caused by enhanced polyol pathway activity via assessment of GL levels in peripheral blood samples from patients.
PubMed: 38879006
DOI: 10.1016/j.jbc.2024.107479