Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular markers in diabetes

Tuttolomondo, Antonino; Maida, Carlo; Pinto, Antonio

doi:10.5312/wjo.v6.i1.62

Cited by 122 publications

(127 citation statements)

References 100 publications

(140 reference statements)

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“…T2DM as a chronic inflammatory state is accompanied by a number of metabolic disturbances. The majority of diabetic patients with DFU present hyperglycemia, insulin resistance, and dyslipidemia which lead to the development and progression of further complications . In the current study, we observed that magnesium and vitamin E co‐supplementation provided a significant improvement in ulcer length, width and depth.…”

Section: Discussionsupporting

confidence: 56%

The effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

Afzali

Kashi

Momen‐Heravi

et al. 2019

Wound Repair Regeneration

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This study was carried out to determine the effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). The current randomized, double-blind, placebo-controlled trial was conducted among 57 patients with grade 3 DFU. Participants were randomly divided into two groups to take either 250 mg magnesium oxide plus 400 IU vitamin E (n = 29) or placebo per day (n = 28) for 12 weeks. Compared with the placebo, taking magnesium plus vitamin E supplements reduced ulcer length (β [difference in the mean of outcomes measures between treatment groups] −0.56 cm; 95% CI, −0.92, −0.20; p = 0.003), width (β −0.35 cm; 95% CI, −0.64, −0.05; p = 0.02) and depth (β −0.18 cm; 95% CI, −0.33, −0.02; p = 0.02). In addition, co-supplementation led to a significant reduction in fasting plasma glucose (β −13.41 mg/dL; 95% CI, −20.96, −5.86; p = 0.001), insulin (β −1.45 μIU/ml; 95% CI, −2.37, −0.52; p = 0.003), insulin resistance (β −0.60; 95% CI, −0.99, −0.20; p = 0.003) and HbA1c (β −0.32%; 95% CI, −0.48, −0.16; p < 0.003), and a significant elevation in insulin sensitivity (β 0.007; 95% CI, 0.003, 0.01; p < 0.001) compared with the placebo. Additionally, compared with the placebo, taking magnesium plus vitamin E supplements decreased triglycerides (β −10.08 mg/dL; 95% CI, −19.70, −0.46; p = 0.04), LDL-cholesterol (β −5.88 mg/dL; 95% CI, −11.42, −0.34; p = 0.03), high sensitivity C-reactive protein (hs-CRP) (β −3.42 mg/L; 95% CI, −4.44, −2.41; p < 0.001) and malondialdehyde (MDA) (β −0.30 μmol/L; 95% CI, −0.45, −0.15; p < 0.001), and increased HDL-cholesterol (β 2.62 mg/dL; 95% CI, 0.60, 4.63; p = 0.01) and total antioxidant capacity (TAC) levels (β 53.61 mmol/L; 95% CI, 4.65, 102.57; p = 0.03). Overall, magnesium and vitamin E co-supplementation for 12 weeks to patients with DFU had beneficial effects on ulcer size, glycemic control, triglycerides, LDL-and HDL-cholesterol, hs-CRP, TAC, and MDA levels.The diabetic foot ulcer (DFU) is a chronic consequence of diabetes mellitus which mainly caused by neuropathy, different grades of ischemia, and infection that coincide with poor glycemic control and diminished neutrophil function. 1 The mortality rate among diabetic patients with DFU is higher than twofold compared with nonulcer patients. 2 Based on the previous evidence, the effective management of diabetes and timely treatment of foot ulcer are implicated for decrease the morbidity and mortality of DFU. 3 The nutritional status of diabetic patients correlates with the severity of ulcer and play an important role in the reversing of wound risk. 4 According to the prior studies, the alternation of magnesium metabolism is a common feature in diabetic patients which interference with glycemic control and contributes to impaired insulin sensitivity and chronic inflammatory status. 5In addition, observational evidence shown that there is an inverse association between magnesium levels and the occurrence of foot ulcers, nephropathy and retinopathy. 6 Similarly, it is repo...

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Section: Discussionsupporting

confidence: 56%

The effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

Afzali

Kashi

Momen‐Heravi

et al. 2019

Wound Repair Regeneration

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“…Hyperglycemia and insulin resistance are associated with an acceleration of arteriosclerotic changes of the greater arteries resulting in decreased blood flow, further contributing to a limb threatening ischemic condition . The diabetic dyslipidemia is one of several factors that contribute to developing macrovascular disease in diabetic patients . Zinc intake may improve parameters of glucose homeostasis through the synthesis, storage, and secretion of monomeric insulin, as well as conversion to dimeric form for storage and secretion as crystalline insulin and participation in insulin action and carbohydrate metabolism .…”

Section: Discussionmentioning

confidence: 99%

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

Momen‐Heravi

Barahimi

Razzaghi

et al. 2017

Wound Repair Regeneration

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This study was performed to determine the effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer. The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 40-85 years old) with grade 3 diabetic foot ulcer. Participants were randomly divided into two groups (30 participants in each group) to take either 220 mg zinc sulfate supplements containing 50 mg elemental zinc or placebo daily for 12 weeks. After the 12-week intervention, compared with the placebo, zinc supplementation was associated with significant reductions in ulcer length (-1.5 ± 0.7 vs. -0.9 ± 1.2 cm, p = 0.02) and width (-1.4 ± 0.8 vs. -0.8 ± 1.0 cm, p = 0.02). In addition, changes in fasting plasma glucose (-40.5 ± 71.0 vs. -3.9 ± 48.5 mg/dl, p = 0.02), serum insulin concentration (-8.0 ± 15.4 vs. +1.1 ± 10.3 µIU/ml, p = 0.009), homeostasis model of assessment-estimated insulin resistance (-3.9 ± 7.1 vs. +0.8 ± 5.9, p = 0.007), the quantitative insulin sensitivity check index (+0.01 ± 0.03 vs. -0.002 ± 0.02, p = 0.04) and HbA1c (-0.5 ± 0.8 vs. -0.1 ± 0.5%, p = 0.01) in the supplemented group were significantly different from the changes in these indicators in the placebo group. Additionally, significant increases in serum HDL-cholesterol (+4.1 ± 4.3 vs. +1.1 ± 5.1 mg/dl, p = 0.01), plasma total antioxidant capacity (+91.7 ± 213.9 vs. -111.9 ± 188.7 mmol/L, p < 0.01) and total glutathione (+68.1 ± 140.8 vs. -35.0 ± 136.1 µmol/L, p = 0.006), and significant decreases in high sensitivity C-reactive protein (-20.4 ± 24.6 vs. -6.8 ± 21.3 µg/ml, p = 0.02) and plasma malondialdehyde concentrations (-0.6 ± 0.9 vs. -0.2 ± 0.7 µmol/L, p = 0.03) were seen following supplementation with zinc compared with the placebo. Zinc supplementation for 12 weeks among diabetic foot ulcer patients had beneficial effects on parameters of ulcer size and metabolic profiles.

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“…A major complication of both type 1 and type 2 diabetes is foot ulceration, and evidence is now emerging to show that diabetes with foot ulceration portends an even higher mortality rate than diabetes alone . This excess mortality remains even after adjusting for chronic kidney disease and known cardiovascular comorbidities .…”

Section: Introductionmentioning

confidence: 99%

Foot ulceration and its association with mortality in diabetes mellitus: a meta‐analysis

et al. 2019

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Background Diabetic foot ulcers portend an almost twofold increase in all-cause mortality compared with diabetes on its own. Aim To investigate the association between diabetic foot ulcers and risk of death. Methods We performed a meta-analysis of all observational studies investigating the association between diabetic foot ulcers and all-cause mortality. Risk ratios and risk differences were pooled in a random-effects model. The I 2 statistic was used to quantify heterogeneity between studies.Results Altogether, we identified 11 studies that reported 84 131 deaths from any cause in 446 916 participants with diabetes during a total of 643 499 person-years of follow-up. The crude event rate for all-cause mortality in individuals with diabetes who did not develop foot ulceration was 22% lower at 181.5 deaths (per 1000 person-years) than in those who developed foot ulcers (230.8 per 1000 person-years). Diabetic foot ulceration was associated with an increased risk of all-cause mortality (pooled relative risk 2.45, 95% CI 1.85-2.85). We did not observe any tangible differences in risk of all-cause mortality from diagnosis in studies reporting a mean duration of follow-up of ≤3 years (relative risk 2.43, 95% CI 2.27-2.61) or >3 years (relative risk 2.26, 95% CI 2.13-2.40) years. Funnel plot inspection revealed no significant publication bias among studies included in this meta-analysis. ConclusionsOur study shows an excess rate of all-cause mortality in people with diabetic foot ulceration when compared to those without foot ulceration. It is imperative that early interventions to prevent foot ulceration and modify cardiovascular disease risk factors are put in place to reduce excess mortality.

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Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular markers in diabetes

Abstract: Diabetic foot ulcerations have

Cited by 122 publications

References 100 publications

The effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

The effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

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

Foot ulceration and its association with mortality in diabetes mellitus: a meta‐analysis

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