Neuropathic diabetic foot ulcers &amp;ndash; evidence-to-practice

Ndip, Agbor; Ebah, Leonard; Mbako, Aloysius

doi:10.2147/ijgm.s10328

Cited by 17 publications

(6 citation statements)

References 41 publications

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“…Some of the major complications of diabetes are peripheral painful diabetic neuropathy (or not painful) and foot ulcers. 47 The delayed wound healing process suffered by patients with diabetes is the major cause of amputations in this population. 3 Macrophages are more abundant in chronic diabetic wounds when compared to acute wounds.…”

Section: Discussionmentioning

confidence: 99%

High glucose induces a priming effect in macrophages and exacerbates the production of pro-inflammatory cytokines after a challenge

Grosick¹,

Alvarado-Vázquez²,

Messersmith³

et al. 2018

JPR

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IntroductionPainful diabetic neuropathy is associated with chronic inflammation, in which macrophages are the key effectors. We utilized an in vitro approach to determine the effects of high glucose on macrophage phenotype.Materials and methodsWe exposed human THP-1 macrophages to normal glucose (5 mM) and a clinically relevant high glucose environment (15 mM) and measured the expression and concentration of molecules associated with a diabetic cellular phenotype.ResultsWe found that THP-1 macrophages in high glucose conditions did not influence the basal expression of cyclooxygenase-2, Toll-like receptor-4, or class A scavenger receptor mRNA, or the concentrations of the cytokines interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and IL-10, but induced a priming effect on tumor necrosis factor (TNF)-α. Then, we stimulated THP-1 macrophages with a strong pro-inflammatory stimulus lipopolysaccharide (LPS; 5 µg/mL). After stimulation with LPS, we observed an exacerbated increase in TNF-α, IL-6, and MCP-1 concentration in the high glucose condition compared to the normal glucose environment. THP-1 macrophages in high glucose conditions developed tolerance to IL-10 anti-inflammatory effects (TNF-α production) when challenged with LPS.ConclusionOur in vitro approach allows the study of macrophages as potential targets for therapeutic purposes since it compares them to primary human macrophages exposed to high glucose and macrophages from patients with diabetes or complications of painful diabetic neuropathy (i.e. ulcers, adipocytes, and pancreas).

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Section: Discussionmentioning

confidence: 99%

High glucose induces a priming effect in macrophages and exacerbates the production of pro-inflammatory cytokines after a challenge

Grosick¹,

Alvarado-Vázquez²,

Messersmith³

et al. 2018

JPR

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“…DPN is the strongest initiating risk factor for diabetic foot ulceration (neuropathic ulcer) (9, 10), and existing ulcers may be further exacerbated from damage to sensory neurones. Resultant limb numbness causes ulcers to remain undetected for longer periods (10); thus, corrective actions are not taken nor advice sought at early stages of the disease. Often the first sign that a person has diabetic peripheral neuropathy (DPN) is a foot ulcer, which may lead to irreversible tissue damage, lower limb amputation and significant morbidity.…”

Section: Introductionmentioning

confidence: 99%

Advances in Screening, Early Diagnosis and Accurate Staging of Diabetic Neuropathy

Carmichael

Fadavi

Ishibashi³

et al. 2021

Front. Endocrinol.

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The incidence of both type 1 and type 2 diabetes is increasing worldwide. Diabetic peripheral neuropathy (DPN) is among the most distressing and costly of all the chronic complications of diabetes and is a cause of significant disability and poor quality of life. This incurs a significant burden on health care costs and society, especially as these young people enter their peak working and earning capacity at the time when diabetes-related complications most often first occur. DPN is often asymptomatic during the early stages; however, once symptoms and overt deficits have developed, it cannot be reversed. Therefore, early diagnosis and timely intervention are essential to prevent the development and progression of diabetic neuropathy. The diagnosis of DPN, the determination of the global prevalence, and incidence rates of DPN remain challenging. The opinions vary about the effectiveness of the expansion of screenings to enable early diagnosis and treatment initiation before disease onset and progression. Although research has evolved over the years, DPN still represents an enormous burden for clinicians and health systems worldwide due to its difficult diagnosis, high costs related to treatment, and the multidisciplinary approach required for effective management. Therefore, there is an unmet need for reliable surrogate biomarkers to monitor the onset and progression of early neuropathic changes in DPN and facilitate drug discovery. In this review paper, the aim was to assess the currently available tests for DPN’s sensitivity and performance.

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“…Diabetic ulcers may be classified as diabetic neuropathic ulcers, diabetic ischemic ulcers and diabetic mixed ulcers; diabetic ischemic ulcers account for ~36% of all diabetic ulcers ( 24 , 25 ). At present dressings seeded with growth factors may be an effective method of treating diabetic neuropathic ulcers; however, there are currently no effective methods of treating diabetic ischemic ulcers ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

A novel dressing seeded with embryonic artery CD133+ cells and loaded with the Sirt1 agonist SRT1720 accelerates the healing of diabetic ischemic ulcers

Cheng

Chen

et al. 2018

Exp Ther Med

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Refractory ischemic ulcers that occur in patients with diabetes present a major clinical challenge. Embryonic artery cluster of differentiation 133+ cells (EACCs) may promote the healing of diabetic ulcers; however, the high glucose environment in the diabetic ulcers decreases the survival rate of transplanted EACCs and inhibit their biological function. Furthermore, microcirculation in diabetic ischemic ulcers is impaired, which inhibits the beneficial effect of EACCs. In the current study, the Sirt1 agonist SRT1720 was selected as a therapeutic drug and loaded into a dressing composed of PLGA, collagen and silk (PCSS) formed using electrospinning technology. EACCs were seeded onto the PCSS dressing and this was used to treat diabetic ulcers. The results indicated that SRT1720 promotes the proliferation of EACCs, enhances the secretion of vascular endothelial growth factor A, interluekin 8 and basic fibroblast growth factor, and inhibits the secretion of tumor necrosis factor α. Furthermore, SRT1720 promoted the paracrine function of EACCs and promoted the proliferation and migration of human umbilical vein endothelial cells. PCSS induced the steady release of SRT1720 over a 15-day period and PCSS seeded with EACCs (PCSS-EACCs) were transplanted into the diabetic ischemic ulcers of mice with diabetes. The results of these experiments indicated that angiogenesis and the healing of diabetic ischemic ulcers was significantly improved following the transplantation of PCSS-EACCs. Therefore, PCSS-EACCs may be a novel and effective treatment for diabetic ischemic ulcers.

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Neuropathic diabetic foot ulcers – evidence-to-practice

Cited by 17 publications

References 41 publications

High glucose induces a priming effect in macrophages and exacerbates the production of pro-inflammatory cytokines after a challenge

High glucose induces a priming effect in macrophages and exacerbates the production of pro-inflammatory cytokines after a challenge

Advances in Screening, Early Diagnosis and Accurate Staging of Diabetic Neuropathy

A novel dressing seeded with embryonic artery CD133+ cells and loaded with the Sirt1 agonist SRT1720 accelerates the healing of diabetic ischemic ulcers

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