Genetic and molecular basis of diabetic foot ulcers: Clinical review.

Published on Nov 1, 2016in Journal of Tissue Viability2.41
· DOI :10.1016/J.JTV.2016.06.005
Shaurya Jhamb1
Estimated H-index: 1
(JCU: James Cook University),
Venkat N. Vangaveti14
Estimated H-index: 14
(JCU: James Cook University),
Usman H. Malabu17
Estimated H-index: 17
(JCU: James Cook University)
Diabetic Foot Ulcers (DFUs) are major complications associated with diabetes and often correlate with peripheral neuropathy, trauma and peripheral vascular disease. It is necessary to understand the molecular and genetic basis of diabetic foot ulcers in order to tailor patient centred care towards particular patient groups. This review aimed to evaluate whether current literature was indicative of an underlying molecular and genetic basis for DFUs and to discuss clinical applications. From a molecular perspective, wound healing is a process that transpires following breach of the skin barrier and is usually mediated by growth factors and cytokines released by specialised cells activated by the immune response, including fibroblasts, endothelial cells, phagocytes, platelets and keratinocytes. Growth factors and cytokines are fundamental in the organisation of the molecular processes involved in making cutaneous wound healing possible. There is a significant role for single nucleotide polymorphism (SNPs) in the fluctuation of these growth factors and cytokines in DFUs. Furthermore, recent evidence suggests a key role for epigenetic mechanisms such as DNA methylation from long standing hyperglycemia and non-coding RNAs in the complex interplay between genes and the environment. Genetic factors and ethnicity can also play a significant role in the development of diabetic neuropathy leading to DFUs. Clinically, interventions which have improved outcomes for people with DFUs or those at risk of DFUs include some systemic therapeutic drug interventions which improve microvascular blood flow, surgical interventions, human growth factors, and hyperbaric oxygen therapy, negative pressure wound therapy, skin replacement or shockwave therapy and the use of topical treatments. Future treatment modalities including stem cell and gene therapies are promising in the therapeutic approach to prevent the progression of chronic diabetic complications.
📖 Papers frequently viewed together
1 Citations
19 Citations
1,389 Citations
Last. David Armstrong (UA: University of Arizona)H-Index: 146
view all 11 authors...
The diabetic foot ulcer (DFU) is the leading cause of lower extremity amputation worldwide and is directly associated with comorbidity, disability and mortality. Oxidative stress mechanisms have been implicated in the pathogenesis of these wounds. Intra-lesional infiltration of epidermal growth factor has emerged as a potential therapeutic alternative to allow for physiological benefit while avoiding the proteolytic environment at the centre of the wound. The aim of this study was to characteris...
18 CitationsSource
#1Agnes Yeboah (RU: Rutgers University)H-Index: 3
#2Rick I. Cohen (RU: Rutgers University)H-Index: 8
Last. Francois Berthiaume (RU: Rutgers University)H-Index: 54
view all 6 authors...
Abstract Chronic skin wounds are characterized by poor re-epithelialization, angiogenesis and granulation. Previous work has demonstrated that topical stromal cell-derived growth factor-1 (SDF1) promotes neovascularization, resulting in faster re-epithelialization of skin wounds in diabetic mice. However, the clinical usefulness of such bioactive peptides is limited because they are rapidly degraded in the wound environment due to high levels of proteases. Here, we describe the development of a ...
30 CitationsSource
Abstract Objective To show an approach to profit of the main components of platelet rich plasma (PRP), i.e. the signaling proteins, and the fibrin scaffold and discuss the intervention within TIME (Tissue, Inflammation/Infection, Moisture, Edges) framework. Methods Two patients with diabetic foot ulcers are treated with both liquid and gelled PRP, and the rationale for the PRP intervention is described herein. Autologous blood is withdrawn and, PRP is separated by single spinning and activated w...
15 CitationsSource
#1Noha Gaber Amin (Alexandria University)H-Index: 2
#2John Doupis (Alexandria University)H-Index: 2
The burden of diabetic foot disease (DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy (DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk f...
81 CitationsSource
#1Apoorva Saboo (JCU: James Cook University)H-Index: 1
#2Ayeshmanthe Rathnayake (JCU: James Cook University)H-Index: 1
Last. Usman H. Malabu (JCU: James Cook University)H-Index: 17
view all 4 authors...
Abstract Objective Dipeptidyl peptidase-4 (DPP-4) inhibitors have a well-known effect on glycaemic control in patients with diabetes but little is known on their wound healing role in this group of population. This paper reviews the effects of DPP-4 inhibitors on wound healing of diabetic foot ulcers. Methods Published data on effects and mechanism of DDP-4 inhibitors on wound healing were derived from Medline, PubMed and Google Scholar search of English language literature from 1994 to 2014 usi...
12 CitationsSource
Abstract Diabetes mellitus (DM) exhibits raised prevalence worldwide. There is a large body of evidence regarding the incidence of DM closely associates with cardiovascular (CV) complications. In this context, hyperglycaemia, oxidant stress, and inflammation are key factors that contribute in CV events and disease in type1 and type 2 DM, even when metabolic control was optimal and/or intensive glycemic control was implemented. It has been suggested that the effect of poor metabolic control or ev...
58 CitationsSource
#1Jonathan Golledge (JCU: James Cook University)H-Index: 72
#2Erik Biros (JCU: James Cook University)H-Index: 24
Last. Smriti M. Krishna (JCU: James Cook University)H-Index: 19
view all 5 authors...
The term epigenetics is usually used to describe inheritable changes in gene function which do not involve changes in the DNA sequence. These typically include non-coding RNAs, DNA methylation and histone modifications. Smoking and older age are recognised risk factors for peripheral artery diseases, such as occlusive lower limb artery disease and abdominal aortic aneurysm, and have been implicated in promoting epigenetic changes. This brief review describes studies that have associated epigenet...
12 CitationsSource
#1Benjamin R. Johnston (Brown University)H-Index: 4
#2Austin Y. HaH-Index: 6
Last. Paul Y. LiuH-Index: 21
view all 4 authors...
Abstract Non-healing wounds are a growing public health concern, and more than $25 billion per year in the US are spent caring for patients with chronic wounds. Many of these patients are referred to specialized wound centers, where hyperbaric oxygen therapy (HBO2T) has become a mainstay in healing wounds, especially diabetic foot ulcers (DFU). However, it is costly, with a typical course of therapy running into the tens of thousands of dollars. Presently, as many as 30-40% of DFU patients with ...
10 Citations
The aim of the present study was to investigate the effect of local insulin injection on granulation tissue formation in the wounds of patients with diabetic foot ulcer. Thirty-two patients with diabetic foot ulcer were randomly divided into an insulin (n=18) and a control (n=14) group. In the diabetic foot ulcer wound, the insulin group were administered insulin and the control group were administered an equal volume of saline. Prior to injection and at 0.5, 1.0, 2.0 and 4.0 h after injection, ...
17 CitationsSource
#1Sergiu-Bogdan Catrina (KI: Karolinska Institutet)H-Index: 19
#2Xiaowei Zheng (KI: Karolinska Institutet)H-Index: 11
Diabetic foot ulceration (DFU) is a chronic complication of diabetes that is characterized by impaired wound healing in the lower extremities. DFU remains a major clinical challenge because of poor understanding of its pathogenic mechanisms. Impaired wound healing in diabetes is characterized by decreased angiogenesis, reduced bone marrow-derived endothelial progenitor cell (EPC) recruitment, and decreased fibroblast and keratinocyte proliferation and migration. Recently, increasing evidence has...
43 CitationsSource
Cited By47
#1Ming Tian (SJTU: Shanghai Jiao Tong University)H-Index: 6
#2Jiaoyun Dong (SJTU: Shanghai Jiao Tong University)H-Index: 7
Last. Huiying Jia (SJTU: Shanghai Jiao Tong University)
view all 4 authors...
We aimed to explore the mechanism of circular RNAs (circRNAs) and provide potential biomarkers for molecular therapy of diabetic foot ulcers (DFU). Gene expression profile of GSE114248, including five normal samples and five DFU samples, was downloaded from GEO database. Differentially expressed circRNAs (DEcircRNAs) between two groups were identified. Then, DEcircRNA-miRNA and miRNA-mRNA interaction was revealed, followed by the circRNA-miRNA-mRNA network construction. Moreover, functional and ...
#1Fernanda Lima Torres de Aquino (UFAL: Federal University of Alagoas)H-Index: 1
#2Juliane Pereira da Silva (UFAL: Federal University of Alagoas)H-Index: 7
Last. Emiliano Barreto (UFAL: Federal University of Alagoas)H-Index: 16
view all 5 authors...
AIM Hydroxycinnamic acids their derivatives have various pharmacological properties. The hydroxycinnamic acid derivatives, methyl cinnamate, trans-cinnamic, and p-coumaric acids have been the object of study in the treatment of skin wounds. However, it is unclear whether these derivatives exert a direct beneficial effect on fibroblast function. In this study, we evaluated the effects of methyl cinnamate, trans-cinnamic, and p-coumaric acids on fibroblast migration in vitro. MATERIALS AND METHODS...
Type 2 diabetes mellitus (T2DM) and its complications pose a serious threat to the life and health of patients around the world. The most dangerous complications of this disease are vascular complications. Microvascular complications of T2DM include retinopathy, nephropathy, and neuropathy. In turn, macrovascular complications include coronary artery disease, peripheral artery disease, and cerebrovascular disease. The currently used diagnostic methods do not ensure detection of the disease at an...
Ethnopharmacological relevance Sophora alopecuroides Linn. (Leguminosae) has been largely used in traditional folk medicine in China as an anti-inflammatory agent and to treat various skin wounds, including sore furunculosis and ulcer (a common type of non-healing wound). The present study aimed to evaluate the effects of S. alopecuroides gel on skin wound healing in rats. Materials and methods When the rats were anesthetized, full-thickness skin wound was performed on dorsal area by using biops...
#1Atta ur Rehman Khan (Donghua University)H-Index: 3
#2Kai Huang (SJTU: Shanghai Jiao Tong University)H-Index: 3
Last. Xiumei Mo (Donghua University)H-Index: 58
view all 9 authors...
Diabetic wound (DW) healing is a major clinical challenge due to multifactorial complications leading to prolonged inflammation. Electrospun nanofibrous (NF) membranes, due to special structural features, are promising biomaterials capable to promote DW healing through the delivery of active agents in a controlled manner. Herein, we report a multifunctional composite NF membrane loaded with ZnO nanoparticles (NP) and oregano essential oil (OEO), employing a new loading strategy, capable to susta...
#1Atta ur Rehman Khan (Donghua University)H-Index: 3
#2Yosry Morsi (Swinburne University of Technology)H-Index: 21
Last. Xiumei Mo (Donghua University)H-Index: 58
view all 7 authors...
A chronic wound in diabetic patients is a major public health concern with socioeconomic and clinical manifestations. The underlying medical condition of diabetic patients deteriorates the wound through physiological, metabolic, molecular, and cellular pathologies. Consequently, a wound enters a vicious pathological inflammatory cycle. Many therapeutic approaches are in practice to manage diabetic wounds hence ensuring the regeneration process. Polymer-based biomaterials have come up with high t...
#1Huanhuan LvH-Index: 2
#2Junyu Liu (NPU: Northwestern Polytechnical University)H-Index: 4
Last. Peng Shang (NPU: Northwestern Polytechnical University)H-Index: 26
view all 7 authors...
Diabetes mellitus (DM) is a chronic metabolic disorder with various complications that poses a huge worldwide healthcare burden. Wounds in diabetes, especially diabetic foot ulcers (DFUs), are difficult to manage, often leading to prolonged wound repair and even amputation. Wound management in people with diabetes is an extremely clinical and social concern. Nowadays, physical interventions gain much attention and have been widely developed in the fields of tissue regeneration and wound healing....
1 CitationsSource
#1Lei ChenH-Index: 8
Last. Wenyuan Liu (CPU: China Pharmaceutical University)H-Index: 16
view all 8 authors...
Abstract Ethnopharmacological relevance Periploca forrestii Schltr. was listed as a classical medicinal plant in “Miao medicine”, which is a branch of traditional Chinese medicine (TCM). According to the theory of TCM, P. forrestii has the efficacy of relaxing tendons and activating collaterals, and dispelling wind and eliminating dampness. Hence, it was often used for the therapy of rheumatoid arthritis and traumatic injury in clinical practice. Aims of the review This review aims to present co...
#1Diana G. Sami (The: American University in Cairo)H-Index: 2
#2Ahmed A. H. Abdellatif (The: American University in Cairo)H-Index: 11
Last. Ahmed Abdellatif (The: American University in Cairo)H-Index: 7
view all 2 authors...
Objective: Pressure ulcers (PUs) are a major healthcare problem, commonly associated with older people, patients who are bedbound and patients with diabetes. The impact of PUs can decrease patients...
2 CitationsSource
A diabetic nonhealing wound causes heavy economic burden and compromised quality of life in patients. The human dermal fibroblast (HDF), which is an important kind of effector cell in the wound healing process, represents different biological behaviors in the normal and diabetic skins. Given this, we attempt to explore functional changes in diabetic skin-derived HDFs and try to find out the "hub" genes that modulate diabetic HDFs and may be the potential therapeutic targets of diabetic wound hea...