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Biomolecules & Biomedicine Sep 2023Modern medicine exhibits an upward trend towards non-invasive methods for early detection of disease and long-term monitoring of patients' health. Diabetes mellitus and... (Review)
Review
Modern medicine exhibits an upward trend towards non-invasive methods for early detection of disease and long-term monitoring of patients' health. Diabetes mellitus and its complications are a promising area for implementation of new medical diagnostic devices. One of the most serious complications of diabetes is diabetic foot ulcer. The main causes responsible for diabetic foot ulcer are ischemia caused by peripheral artery disease and diabetic neuropathy caused by polyol pathway-induced oxidative stress. Autonomic neuropathy impairs function of sweat glands, which can be measured by electrodermal activity. On the other hand, autonomic neuropathy leads to changes in heart rate variability, which is used to assess autonomic regulation of the sinoatrial node. Both methods are enough sensitive to detect pathological changes caused by autonomic neuropathy and are promising screening methods for early diagnosis of diabetic neuropathy, which could prevent the onset of diabetic ulcer.
Topics: Humans; Diabetic Neuropathies; Diabetic Foot; Heart Rate; Galvanic Skin Response; Diabetes Mellitus, Type 2
PubMed: 36803545
DOI: 10.17305/bb.2022.8561 -
International Wound Journal Feb 2024Diabetic foot ulcers (DFU), diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) are common complications of diabetes mellitus, while diabetic...
Diabetic foot ulcers (DFU), diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) are common complications of diabetes mellitus, while diabetic peripheral neuropathy and peripheral arterial disease contribute to the pathogenesis of diabetic foot ulcers, and the pathogenic mechanisms between these three diseases still need further investigation. The keywords 'diabetic foot ulcer', 'diabetic peripheral neuropathy' and 'atherosclerosis' were used to search for related gene sets in the GEO database. Differentially expressed genes (DEGs) were screened and analysed for GO, KEGG and enrichR functional enrichment. Potential three disease biomarkers were identified by SVM-SVM-RFE and LASSO regression analysis. The results were also validated using external datasets and discriminability was measured by area under the ROC curve (AUC). Finally, biomarkers and co-upregulated genes were analysed through the GSEA and Attie Laboratories diabetes databases. A total of 11 shared genes (KRT16, CD24, SAMD9L, SRGAP2, FGL2, GPR34, DDIT4, NFE2L3, FBLN5, ANXA3 and CPA3), two biomarkers (SAMD9L and FGL2) and one co-upregulated gene (CD24) were screened. GO and KEGG pathway analysis of DEGs, enrichr enrichment analysis of shared differential genes and GSEA analysis of biomarkers showed that these significant genes were mainly focused on vasoregulatory, inflammatory-oxidative stress and immunomodulatory pathways. In this study, we used bioinformatics to investigate the intrinsic relationship and potential mechanisms of three common lower extremity complications of diabetes and identified two pivotal genes using the LASSO model and the SVM-RFE algorithm, which will further help clinicians to understand the relationship between diabetic complications, improve the diagnosis and treatment of diabetic foot problems and help doctors to identify the potential risk factors of diabetic foot.
Topics: Humans; Diabetic Foot; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Foot Ulcer; Peripheral Arterial Disease; Biomarkers; Basic-Leucine Zipper Transcription Factors; Fibrinogen; GTPase-Activating Proteins
PubMed: 38358067
DOI: 10.1111/iwj.14748 -
Journal of Foot and Ankle Research Sep 2023Lower limb oedema is a common co-morbidity in those with diabetes and foot ulceration and is linked with increased amputation risk. There is no current guidance for the... (Review)
Review
BACKGROUND
Lower limb oedema is a common co-morbidity in those with diabetes and foot ulceration and is linked with increased amputation risk. There is no current guidance for the treatment of concurrent diabetic foot ulcers and lower limb oedema, leading to uncertainty around the safety and efficacy of combination approaches incorporating offloading and compression therapies. To determine indications and contraindications for such strategies and identify any other supplementary treatment approaches, a scoping review was undertaken to map the evidence relating to off-loading and compression therapy strategies to treat both diabetic foot ulcers and lower limb oedema in combination.
METHODS
Following the Joanna Briggs Institute (JBI) and PRISMA - Scoping Review (ScR) guidance, this review included published and unpublished literature from inception to April 2022. Literature was sourced using electronic databases including Cochrane Library, PubMed, CINAHL, AMED; websites; professional journals and reference lists of included literature. Eligible literature discussed the management of both diabetic foot ulceration and lower limb oedema and included at least one of the treatment strategies of interest. Data extraction involved recording any suggested off-loading, compression therapy or supplementary treatment strategies and any suggested indications, contraindications and cautions for their use.
RESULTS
Five hundred twenty-two publications were found relating to the management of diabetic foot ulcers with an off-loading strategy or the management of lower limb oedema with compression therapy. 51 publications were eligible for inclusion in the review. The majority of the excluded publications did not discuss the situation where diabetic foot ulceration and lower limb oedema present concurrently.
CONCLUSIONS
Most literature, focused on oedema management with compression therapy to conclude that compression therapy should be avoided in the presence of severe peripheral arterial disease. Less literature was found regarding off-loading strategies, but it was recommended that knee-high devices should be used with caution when off-loading diabetic foot ulcers in those with lower limb oedema. Treatment options to manage both conditions concurrently was identified as a research gap. Integrated working between specialist healthcare teams, was the supplementary strategy most frequently recommended. In the absence of a definitive treatment solution, clinicians are encouraged to use clinical reasoning along with support from specialist peers to establish the best, individualised treatment approach for their patients.
TRIAL REGISTRATION
Open Science Framework (osf.io/crb78).
Topics: Humans; Diabetic Foot; Amputation, Surgical; Databases, Factual; Edema; Evidence Gaps; Diabetes Mellitus
PubMed: 37674176
DOI: 10.1186/s13047-023-00659-3 -
Advanced Drug Delivery Reviews Dec 2023Diabetic foot ulcers (DFUs) are a devastating complication for diabetic patients that have debilitating effects and can ultimately lead to limb amputation. Healthy... (Review)
Review
Diabetic foot ulcers (DFUs) are a devastating complication for diabetic patients that have debilitating effects and can ultimately lead to limb amputation. Healthy wounds progress through the phases of healing leading to tissue regeneration and restoration of the barrier function of the skin. In contrast, in diabetic patients dysregulation of these phases leads to chronic, non-healing wounds. In particular, unresolved inflammation in the DFU microenvironment has been identified as a key facet of chronic wounds in hyperglyceamic patients, as DFUs fail to progress beyond the inflammatory phase and towards resolution. Thus, control over and modulation of the inflammatory response is a promising therapeutic avenue for DFU treatment. This review discusses the current state-of-the art regarding control of the inflammatory response in the DFU microenvironment, with a specific focus on the development of biomaterials-based delivery strategies and their cargos to direct tissue regeneration in the DFU microenvironment.
Topics: Humans; Diabetic Foot; Wound Healing; Skin; Inflammation; Diabetes Mellitus
PubMed: 37884128
DOI: 10.1016/j.addr.2023.115120 -
Medicina (Kaunas, Lithuania) Jul 2023: Worldwide, approximately 500 million people suffer from diabetes and at least 50% of these people develop neuropathy. Currently, therapeutic strategies for reducing...
: Worldwide, approximately 500 million people suffer from diabetes and at least 50% of these people develop neuropathy. Currently, therapeutic strategies for reducing diabetic neuropathy (DN)-associated pain are limited and have several side effects. The purpose of the study was to evaluate the antihyperalgesic action of different sildenafil (phosphodiesterase-5 inhibitor) and metformin (antihyperglycemic agent) combinations in alloxan-induced DN. : The study included 100 diabetic mice and 20 non-diabetic mice that were subjected to hot and cold stimulus tests. Furthermore, we determined the influence of this combination on TNF-α, IL-6 and nitrites levels in brain and liver tissues. : In both the hot-plate and tail withdrawal test, all sildenafil-metformin combinations administered in our study showed a significant increase in pain reaction latencies when compared to the diabetic control group. Furthermore, all combinations decreased blood glucose levels due to the hypoglycemic effect of metformin. Additionally, changes in nitrite levels and pro-inflammatory cytokines (TNF-α and IL-6) were observed after 14 days of treatment with different sildenafil-metformin combinations. : The combination of these two substances increased the pain reaction latency of diabetic animals in a dose-dependent manner. Moreover, all sildenafil-metformin combinations significantly reduced the concentration of nitrites in the brain and liver, which are final products formed under the action of iNOS.
Topics: Mice; Animals; Diabetic Neuropathies; Hyperalgesia; Metformin; Sildenafil Citrate; Interleukin-6; Nitrites; Tumor Necrosis Factor-alpha; Pain; Hypoglycemic Agents; Biomarkers; Diabetes Mellitus
PubMed: 37629665
DOI: 10.3390/medicina59081375 -
Diabetes Research and Clinical Practice Dec 2023High frequency spinal cord stimulation (SCS) is a safe and effective treatment option for refractory painful diabetic neuropathy and should be considered for use early...
High frequency spinal cord stimulation (SCS) is a safe and effective treatment option for refractory painful diabetic neuropathy and should be considered for use early in the course of the disease. Raising awareness of this minimally invasive treatment option among physician networks is of major importance.
Topics: Humans; Spinal Cord Stimulation; Pain Management; Diabetic Neuropathies; Treatment Outcome
PubMed: 38245320
DOI: 10.1016/j.diabres.2023.110754 -
Chirurgia (Bucharest, Romania : 1990) Dec 2023Diabetes Mellitus represents a major socio-economic issue both by influencing the patient's quality of life and also considering the impact on the healthcare system....
Diabetes Mellitus represents a major socio-economic issue both by influencing the patient's quality of life and also considering the impact on the healthcare system. Diabetic neuropathy is one of the main complications associated, in most cases being present from the moment of diagnosis. Considering the high incidence of diabetes among patients with biliodigestive surgical conditions, a thorough analysis of the evolution and management of these patients is necessary. The association between the evolution of diabetic patients with biliodigestive conditions and diabetic neuropathy as well as risk criteria and associated complications were analyzed in a descriptive, correlational study (314 patients) conducted in the Dr. I. Cantacuzino Clinical Hospital during 2020-2022. In the study, the patients were distributed into two groups, one consisting in patients without diabetes mellitus (control group) and the second further subdivided into two groups of study, first (2a) containing patients with type II with diabetic neuropathy and high and medium risk rate, and a second one (2b) including patients with diabetes mellitus type II with confirmed neuropathy and low risk rate. Clinical and laboratory evaluations were performed and management protocols applied. Statistically significant correlations were highlighted between diabetic neuropathy and the variables tested which were subsequently combined to achieve a risk score and a management protocol. Diabetes mellitus associated with diabetic neuropathy represents a negative prognostic factor for the postoperative outcome being associated with high risk of morbidity and mortality. The risk score and the management protocol described as results of this study represent feasible solutions and a subservient instrument in preventing the occurrence of complications in patients with bilio-digestive surgical pathologies in order to improve the prognosis and survival of the patients.
Topics: Humans; Diabetic Neuropathies; Quality of Life; Treatment Outcome; Diabetes Mellitus, Type 2; Risk Factors
PubMed: 38228593
DOI: 10.21614/chirurgia.2023.v.118.i.6.p.609 -
Journal of Diabetes Mar 2024Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes mellitus (T2DM), which frequently results in disabling neuropathic pain and lower-limb...
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes mellitus (T2DM), which frequently results in disabling neuropathic pain and lower-limb amputation. The identification of noninvasive biomarkers for DPN may help early detection and individualized treatment of DPN.
METHODS
In this study, we identified differentially expressed genes (DEGs) between DPN and the control based on blood-source (GSE95849) and tissue-source gene expression profiles (GSE143979) from the Gene Expression Omnibus (GEO) database using limma, edgeR, and DESeq2 approaches. KEGGG and GO functional enrichments were performed. Hub genes and their correlation with infiltrating immune cells were analyzed. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify hub gene expression.
RESULTS
In total, 144 DEGs between DPN and the control were identified. Functional enrichment revealed that the DEGs were mainly enriched in immune-related pathways like the Fc epsilon receptor Ig signaling pathway. By protein-protein interaction (PPI) network analysis, FCER1G, SYK, ITGA4, F13A1, MS4A2, and PTK2B were screened as hub genes with higher expression in DPN patients, among which half were immune genes (FCER1G, PTK2B, and SYK). RT-qPCR demonstrated that mRNA expression of FCER1G, PTK2B, and SYK was significantly increased in patients with DPN compared with both diabetic nonperipheral neuropathy (DNN) and normal subjects. The area under the receiver operating characteristic (ROC) curve of FCER1G, PTK2B, and SYK was 0.84, 0.81, and 0.73, respectively, suggesting their great advantages as diagnostic biomarkers to predict the progression of neuropathy in T2DM. Further analysis indicated that the expression of FCER1G, PTK2B, and SYK was negatively correlated with the cell proportion of significantly altered resting natural killer cells, T follicular helper cells, and activated mast cells, but positively correlated with monocytes.
CONCLUSIONS
Our findings demonstrated FCER1G, PTK2B, and SYK are potential diagnostic biomarkers and therapeutic targets for DPN, which provides new insight into DPN pathogenesis and therapies.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Amputation, Surgical; Computational Biology; Databases, Factual
PubMed: 38018513
DOI: 10.1111/1753-0407.13506 -
Stem Cells Translational Medicine Oct 2023Diabetic foot ulcer (DFU) is a main diabetic complication with unmet treatment needs. This study applied human umbilical cord-derived mesenchymal stem cells-hyaluronic...
External Application of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Hyaluronic Acid Gel Repairs Foot Wounds of Types I and II Diabetic Rats Through Paracrine Action Mode.
Diabetic foot ulcer (DFU) is a main diabetic complication with unmet treatment needs. This study applied human umbilical cord-derived mesenchymal stem cells-hyaluronic acid (hucMSCs-HA) gel to treat DFU in a noninvasive external way and investigated its paracrine action and mechanism. In this study, after analyzing the physical and biological properties of HA gel, hucMSCs-HA gel was applied in 2 in vivo models (types I and II DFU), and a molecular mechanism was investigated. To evaluate the paracrine action of hucMSCs, hucMSCs-conditional medium (MSC-CM) was collected to treat 1 in vivo model (type I DFU) and 2 in vitro models (high glucose (HG)-injured human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs)). The results indicated that HA gel with a porous microstructure underwent over 90% degradation and swelled to the maximum value within 48 h. In vivo, hucMSCs-HA gel accelerated wound healing of DFU rats by improving re-epithelialization, collagen deposition, and angiogenesis, in which a paracrine action of hucMSCs was confirmed and the phosphorylation of p38, ERK1/2, JNK, and Akt was increased. In vitro, MSC-CM improved cell viability, wound healing, migration, tube formation, cell senescence, and abnormal expressions (TNF-α, IL-1β, IL-6, ET-1, p16 genes, and PCNA protein) of HUVECs, also improved cell viability, wound healing, antioxidant stress, and abnormal expressions (COL1, COL3, COL4, SOD1, SOD2 genes, and PCNA protein) of HSFs. Summarily, noninvasive external application of hucMSCs-HA gel shows great perspective against DFU and exerts wound healing effects through the MAPK and Akt pathways-mediated paracrine mechanism.
Topics: Humans; Rats; Animals; Hyaluronic Acid; Diabetes Mellitus, Experimental; Proto-Oncogene Proteins c-akt; Proliferating Cell Nuclear Antigen; Human Umbilical Vein Endothelial Cells; Mesenchymal Stem Cells; Umbilical Cord; Diabetic Foot
PubMed: 37639574
DOI: 10.1093/stcltm/szad050 -
Foot (Edinburgh, Scotland) Sep 2023Diabetic foot amputations are a devastating outcome for any diabetic patient. They are associated with various risk factors, including failure to risk stratify the...
Diabetic foot and lower limb amputations at central, provincial and tertiary hospitals-underscores the need for organised foot health services at primary healthcare level.
BACKGROUND
Diabetic foot amputations are a devastating outcome for any diabetic patient. They are associated with various risk factors, including failure to risk stratify the diabetic foot. Early risk stratification could lower foot complications risk at the primary healthcare level (PHC). In the Republic of South Africa (RSA), PHC clinics are the first entry point to the public healthcare system. Failure to correctly identify, risk categorise, and refer diabetic foot complications at this level may lead to poor clinical outcomes for diabetic patients. This study looks at the incidence of diabetic-related amputations at central and tertiary hospitals in Gauteng to highlight the case of the needed foot health services at the PHC level.
METHODS
A cross-sectional retrospective study that reviewed prospectively collected theatre records database of all patients who underwent a diabetic-related foot and lower limb amputation between January 2017 and June 2019. Inferential and descriptive statistics were performed, and patient demographics, risk factors and type of amputation were reviewed.
RESULTS
There were 1862 diabetic-related amputations in the period under review. Most patients (98 %) came from a poor socioeconomic background earning ZAR 0.00-70 000.00 (USD 0.00-4754.41) per annum. Most amputations, 62 % were in males, and the majority, 71 % of amputations, were in patients younger than 65. The first amputation was major in 73 % of the cases, and an infected foot ulcer was a primary amputation cause in 75 % of patients.
CONCLUSION
Amputations are a sign of poor clinical outcomes for diabetic patients. Due to the hierarchal nature of healthcare delivery in RSA, diabetic-related foot amputations could imply inadequate care of or access to diabetic foot complications at the PHC level in RSA. A lack of access to structured foot health services at PHC levels impedes early identification of foot complication identification and appropriate referral resulting in amputation in some of the patients.
Topics: Male; Humans; Diabetic Foot; Retrospective Studies; Tertiary Care Centers; Cross-Sectional Studies; South Africa; Lower Extremity; Amputation, Surgical; Health Services; Primary Health Care; Diabetes Mellitus
PubMed: 37244198
DOI: 10.1016/j.foot.2023.102039