Glycemic control and diabetic foot ulcer outcomes: A systematic review and meta-analysis of observational studies

Lane, Kyrstin; Abusamaan, Mohammed S.; Voss, Betiel Fesseha; Thurber, Emilia G.; Alhajri, Noora; Gopakumar, Shraddha; Lê, Jimmy T.; Gill, Sharoon; Blanck, Jaime Friel; Prichett, Laura; Hicks, Caitlin W.; Sherman, Ronald L.; Abularrage, Christopher J.; Mathioudakis, Nestoras

doi:10.1016/j.jdiacomp.2020.107638

Cited by 64 publications

(41 citation statements)

References 70 publications

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“…Furthermore, skin keratinocytes exposed to high glucose also exhibit abnormal cellular morphology, insulin resistance, and decreased proliferation (66,210). Taken together these experimental data support the clinical statement that abnormal levels of glycated hemoglobin and fasting glucose, are associated to poor ulcers healing and higher figures of lower extremity amputation in diabetics (211). Conclusively, fibroblast, endothelial cells, and keratinocytes -the most important cells for skin injury repair-are sensitive to hyperglycemia and oxidative stress, which act as the main steering factors toward senescence (202,212).…”

Section: Cellular Senescence In Diabetic Sweet Environmentsupporting

confidence: 60%

Cellular Senescence as the Pathogenic Hub of Diabetes-Related Wound Chronicity

et al. 2020

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Diabetes is constantly increasing at a rate that outpaces genetic variation and approaches to pandemic magnitude. Skin cells physiology and the cutaneous healing response are progressively undermined in diabetes which predisposes to lower limb ulceration, recidivism, and subsequent lower extremities amputation as a frightened complication. The molecular operators whereby diabetes reduces tissues resilience and hampers the repair mechanisms remain elusive. We have accrued the notion that diabetic environment embraces preconditioning factors that definitively propel premature cellular senescence, and that ulcer cells senescence impair the healing response. Hyperglycemia/oxidative stress/mitochondrial and DNA damage may act as major drivers sculpturing the senescent phenotype. We review here historical and recent evidences that substantiate the hypothesis that diabetic foot ulcers healing trajectory, is definitively impinged by a self-expanding and self-perpetuative senescent cells society that drives wound chronicity. This society may be fostered by a diabetic archetypal secretome that induces replicative senescence in dermal fibroblasts, endothelial cells, and keratinocytes. Mesenchymal stem cells are also susceptible to major diabetic senescence drivers, which accounts for the inability of these cells to appropriately assist in diabetics wound healing. Thus, the use of autologous stem cells has not translated in significant clinical outcomes. Novel and multifaceted therapeutic approaches are required to pharmacologically mitigate the diabetic cellular senescence operators and reduce the secondary multi-organs complications. The senescent cells society and its adjunctive secretome could be an ideal local target to manipulate diabetic ulcers and prevent wound chronification and acute recidivism. This futuristic goal demands harnessing the diabetic wound chronicity epigenomic signature.

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Section: Cellular Senescence In Diabetic Sweet Environmentsupporting

confidence: 60%

Cellular Senescence as the Pathogenic Hub of Diabetes-Related Wound Chronicity

et al. 2020

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“…This is the important observation made by authors and which could be considered while applying results of this evidence into practice or while conducting further RCTs on this area. The common associated factors that are well established for amputations among patients with non-healing DFU are: chronic arterial insufficiency 41 , neuroischemic foot 42 , poor glycaemic control 43 and infection 44 . HBOT helps to accomplish physiological effects by declining ischemia at regional as well as local tissues.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of hyperbaric oxygen therapy for diabetic foot ulcer, a systematic review and meta-analysis of controlled clinical trials

Sharma

Mudgal

et al. 2021

Sci Rep

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Studies have suggested that hyperbaric oxygen therapy (HBOT) is effective in the healing of diabetic foot ulcer (DFU); however, there is a lack of consensus. Therefore, to assess the efficacy of HBOT on diabetic foot ulcer among diabetic patients, controlled clinical trials were searched through PubMed, EMBASE, Clinical key, Ovid Discovery, ERMED, Clinical Trials.gov databases for randomized controlled trials (RCTs) and other sources until 15 September 2020. Studies that evaluated the effect of HBOT on diabetic foot ulcer, complete healing, amputation, adverse events, ulcer reduction area, and mortality rate were included. Of 1984 study records screened, 14 studies (768 participants) including twelve RCTs, and two CCTs were included as per inclusion criteria. The results with pooled analysis have shown that HBOT was significantly effective in complete healing of diabetic foot ulcer (OR = 0.29; 95% CI 0.14–0.61; I2 = 62%) and reduction of major amputation (RR = 0.60; 95% CI 0.39–0.92; I2 = 24%). Although, it was not effective for minor amputations (RR = 0.82; 95% CI 0.34–1.97; I2 = 79%); however, less adverse events were reported in standard treatment group (RR = 1.68; 95% CI 1.07–2.65; I2 = 0%). Nevertheless, reduction in mean percentage of ulcer area and mortality rate did not differ in HBOT and control groups. This review provides an evidence that hyperbaric oxygen therapy is effective as an adjunct treatment measure for the diabetes foot ulcers. These findings could be generalized cautiously by considering methodological flaws within all studies.

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“…In addition, lack of diabetes control and hyperlipidemia are factors that affect the severity of DFU (Jalilian et al, 2020). Also it is confirmed that hyperglycemia elevates the likelihood of amputation in DFU (Lane et al, 2020). Evidence has demonstrated that the management of glycemic status in DFU patients is associated with decreased amputation risk (Hasan et al, 2016).…”

Section: Discussionmentioning

confidence: 86%

The effects of curcumin intake on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

Mokhtari

Razzaghi

Momen‐Heravi

2020

Phytotherapy Research

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This study was conducted to determine the effects of curcumin intake on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). The current randomized, double‐blind, placebo‐controlled trial was conducted among 60 patients with grade 3 DFU. Participants were randomly allocated into two groups (30 participants each group), received either 80 mg nanocurcumin daily for 12 weeks or placebo. Primary endpoints in this study were serum insulin levels and insulin resistance. Curcumin intake significantly decreased fasting plasma glucose (p = .02), insulin (p = .01), insulin resistance (p = .02), and significantly increased insulin sensitivity (p = .008) compared with the placebo. Moreover, curcumin intake led to a significant reduction in total‐ (p < .001), LDL‐cholesterol (p < .001), and a significant increase in total antioxidant capacity (TAC) (p < .001) and total glutathione (GSH) (p = .01) compared with the placebo. However, there was no significant improvement in wound healing parameters. Overall, our study demonstrated that nanocurcumin intake in patients with DFU resulted in a significant improvement of glycemic control, total‐ and LDL‐cholesterol, TAC, and GSH but did not affect the indicators of ulcer size.

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Glycemic control and diabetic foot ulcer outcomes: A systematic review and meta-analysis of observational studies

Cited by 64 publications

References 70 publications

Cellular Senescence as the Pathogenic Hub of Diabetes-Related Wound Chronicity

Cellular Senescence as the Pathogenic Hub of Diabetes-Related Wound Chronicity

Efficacy of hyperbaric oxygen therapy for diabetic foot ulcer, a systematic review and meta-analysis of controlled clinical trials

The effects of curcumin intake on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

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