Microangiopathy: Is it relevant to wound healing in diabetic foot disease?

Sharma, Sanjeev; Schaper, Nicolaas C.; Rayman, Gerry

doi:10.1002/dmrr.3244

Cited by 46 publications

(35 citation statements)

References 33 publications

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“…However, it is not going well, especially the management of diabetic complications, such as DFCs 21,22 . A previous study reported that the overall [23][24][25] . In our study, we observed a strong relationship between FHD and DFCs, especially of the different numbers of relatives with diabetes, in which the number of patients with one and more than 1 relative with diabetes led to 1.377-and 1.402-fold increases in the risk of DFCs, respectively, compared with those without FHD.…”

Section: Discussionmentioning

confidence: 99%

Family history of diabetes is associated with diabetic foot complications in type 2 diabetes

Xiong

Wei

Xiao

et al. 2020

Sci Rep

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To investigate the relationship between diabetic foot complications (DFCs) and clinical characteristics, especially the number and types of first-degree family members with diabetes. A total of 8909 type 2 diabetes patients were enrolled. The clinical characteristics of these patients, including DFCs and family history of diabetes (FHD), were collected from medical records. Multiple regression was used to investigate the association between FHD and DFCs after adjusting for confounding factors. The patients with one and more than one first-degree family member with diabetes accounted for 18.7% and 12.8%, respectively. The proportions of the participants with a father with diabetes, a mother with diabetes, both parents with diabetes, siblings with diabetes, father and siblings with diabetes, mother and siblings with diabetes, and both parents and siblings with diabetes were 3.5%, 6.2%, 1.1%, 14.4%, 1.5%, 4%, and 0.7%, respectively. The multiple regression analysis showed that the number of family members with diabetes was positively associated with DFCs. However, among the different types of FHD, only the patients with a mother with diabetes showed a statistical association with DFCs. In addition to FHD, other factors, including gender, body mass index, platelet count, hemoglobin levels, albumin levels, high-density cholesterol levels, diabetic peripheral neuropathy, and the use of lipid-lowering agents, oral hypoglycemic agents, and insulin, were also associated with DFCs. DFCs were associated with different numbers of family members with diabetes and types of FHD. This association reveals the importance of genetic and environmental factors in DFCs and highlights the importance of adding FHD to public health strategies targeting detecting and preventing the disease.

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Section: Discussionmentioning

confidence: 99%

Family history of diabetes is associated with diabetic foot complications in type 2 diabetes

Xiong

Wei

Xiao

et al. 2020

Sci Rep

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“…A preexisting microangiopathic disease burden (and markers thereof, e.g. poor glycaemic control and duration of diabetes) are strong risk factors for disease severity ( 54 ). TMA is reported as a frequent event in Covid-19 and is likely to involve endothelium-mediated complement activation ( 55 ).…”

Section: Covid-19 and Thrombotic Microangiopathymentioning

confidence: 99%

Covid-19 and Diabetes: A Complex Bidirectional Relationship

et al. 2020

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Covid-19 is a recently-emerged infectious disease caused by the novel severe acute respiratory syndrome coronavirus SARS-CoV2. SARS-CoV2 differs from previous coronavirus infections (SARS and MERS) due to its high infectivity (reproduction value, R 0 , typically 2–4) and pre- or asymptomatic transmission, properties that have contributed to the current global Covid-19 pandemic. Identified risk factors for disease severity and death from SARS-Cov2 infection include older age, male sex, diabetes, obesity and hypertension. The reasons for these associations are still largely obscure. Evidence is also emerging that SARS-CoV2 infection exacerbates the underlying pathophysiology of hyperglycemia in people with diabetes. Here, we discuss potential mechanisms through which diabetes may affect the risk of more severe outcomes in Covid-19 and, additionally, how diabetic emergencies and longer term pathology may be aggravated by infection with the virus. We consider roles for the immune system, the observed phenomenon of microangiopathy in severe Covid-19 infection and the potential for direct viral toxicity on metabolically-relevant tissues including pancreatic beta cells and targets of insulin action.

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“…Angiogenesis plays a significant role during the dynamic process of wound healing. In fact, DFU show areas of local skin ischemia with severely impaired blood flow ( Falanga, 2005 ; Sharma et al, 2020 ). Therefore, therapeutic angiogenesis, which aims at stimulating neovascularization through local delivery of angiogenic factors to improve the perfusion of ischemic tissue, is an attractive treatment strategy.…”

Section: Introductionmentioning

confidence: 99%

Robust Angiogenesis and Arteriogenesis in the Skin of Diabetic Mice by Transient Delivery of Engineered VEGF and PDGF-BB Proteins in Fibrin Hydrogels

Certelli

Valente

Uccelli

et al. 2021

Front. Bioeng. Biotechnol.

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Non-healing ulcers are a serious complication of diabetes mellitus and a major unmet medical need. A major cause for the lack of healing is the impairment of spontaneous vascularization in the skin, despite mostly normal blood flow in deeper large vessels. Therefore, pro-angiogenic treatments are needed to increase therapeutic perfusion by recruiting new arterial connections (therapeutic arteriogenesis). Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis in physiology and disease, but exploitation of its therapeutic potential requires careful control of its dose distribution in tissue. Co-delivery of platelet derived growth factor-BB (PDGF-BB) has been shown to expand the therapeutic window of VEGF and also improve associated arteriogenesis. We used a highly controlled protein delivery system, based on a clinically applicable fibrin-based platform, to investigate the angiogenic and arteriogenic potential of engineered versions (TG-) of VEGF and PDGF-BB proteins in the skin of diabetic and obese db/db mice. Intradermal delivery of therapeutically relevant doses of TG-VEGF and TG-PDGF-BB induced robust growth of new microvascular networks with similar efficacy as in normal littermate control mice. Further, TG-PDGF-BB prevented the formation of aberrant vascular enlargements by high TG-VEGF levels. As fibrin was degraded after the first week, the induced angiogenesis mostly regressed by 4 weeks, but it promoted effective arteriogenesis in the dermal layer. Therefore, controlled co-delivery of TG-VEGF and TG-PDGF-BB recombinant proteins is effective to induce angiogenesis and arteriogenesis in diabetic mouse skin and should be further investigated to promote diabetic wound healing.

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Microangiopathy: Is it relevant to wound healing in diabetic foot disease?

Cited by 46 publications

References 33 publications

Family history of diabetes is associated with diabetic foot complications in type 2 diabetes

Family history of diabetes is associated with diabetic foot complications in type 2 diabetes

Covid-19 and Diabetes: A Complex Bidirectional Relationship

Robust Angiogenesis and Arteriogenesis in the Skin of Diabetic Mice by Transient Delivery of Engineered VEGF and PDGF-BB Proteins in Fibrin Hydrogels

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