Article

Targeted Amino Acid Supplementation in Diabetic Foot Wounds: Pilot Data and a Review of the Literature

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Abstract

Background: Diabetic foot wounds are a highly morbid and costly complication of diabetes mellitus. Targeted amino acid supplementation, by increasing tissue hydroxyproline concentrations, has been implicated in improved wound outcomes in surgical incisions and chronic wounds, and after radiation injury. A major component of collagen, hydroxyproline is a surrogate marker used commonly for tissue collagen concentrations. This paper reviews the literature pertaining to amino acid supplementation and wound healing, and also evaluates our pilot data relating to supplementation with arginine, glutamine, and beta-hydroxy-beta-methylbutyrate (HMB) in the treatment of diabetic foot ulcers. Methods: For the pilot study, nine patients scheduled to undergo wound debridement for diabetic foot ulcers were randomized prospectively to be a part of either a placebo group or a treatment group that received supplementation twice daily for 2 wks. Tissue samples were collected both before and after 2 wk of supplementation. The results of assay of the samples for hydroyproline were then analyzed via a one tailed Student t-test to evaluate tissue concentrations of hydroxyproline. For the literature review in the study, the MEDLINE/PubMed database was reviewed, using search terms contained in the Medical Subject Headings (MeSH). Results: The treatment group in the study exhibited a significantly greater hydroxyproline concentration after supplementation than before it (p=0.03). The mean percent change in the tissue hydroxyproline concentration for arginine, glutamine, and HMB group was +67.8%, with a standard deviation (SD) of 129.89. The mean percent change for the corresponding amino acids in the placebo group was -78.4%, with an SD of 20.55. The review of the MEDLINE/PubMed literature revealed only two human studies of amino acid supplementation in patients with diabetic foot wounds, one of which found a significant improvement in wound-depth and wound-appearance scores. Conclusions: Given the results of our pilot study, and on the basis of a review of the literature, the administration of a simple amino acid supplement may improve the healing of diabetic foot wounds via increased collagen production.

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... Finally, 41 articles were suitable and included in the present review ( Figure 1). 17 Among the 41 articles included, 9 articles were systematic reviews referring to multiple diet models and nutrients in association to DFUs, 15,16,[18][19][20][21][22][23][24] 5 articles examined the effect of combine nutrients or diet characteristics (2 were cross-sectional, 12, 25 1 was a case control study, 26 2 were prospective cohort studies 14,27 ), 5 articles examined the association of the nutritional status or malnutrition with DFUs (3 were prospective, observational cohort studies, 28-30 1 was a cross-sectional study 31 and 1 was a retrospective cohort study 32 ), 3 studies research the effect of specific vitamins (1 case control study on B12, 33 1 retrospective cohort study on high folic acid dose, 34 1 randomized clinical trial [RCT] on vitamin C 35 ), 5 articles were RCT that studied the supplementation with protein and/or amino acids plus vitamins and minerals, [36][37][38][39][40] 7 articles referred to the association of vitamin D with DFUs (4 were systematic literature reviews, [41][42][43] 1 was a prospective cohort study, 44 1 was a RCT 45 and 2 were cross-sectional studies 46,47 ), 2 articles were RCTs examined the effect of magnesium supplementation, 48,49 1 article was a RCT about omega-3 fatty acids supplementation, 50 1 article was also a RCT about probiotic supplementation, 51 1 article was a RCT about zinc supplementation, 52 and 2 articles, 1 review 53 and 1 RCT, 54 examine the effect of herbal supplements or supplements with antioxidant compounds (Table 1). ...
... 37 In another RCT, significantly (P=.03) higher hydroxyproline concentration was seen after arginine and glutamine supplementation. 38 This study has linked arginine, ...
... 65 Among DFUs patients, the current review found supplementation with protein and/or amino acids and other micronutrients to be valuable, but only in cases of malnutrition or deficiencies. [36][37][38]40 For this reason, frequent diet assessment of patients with DFUs and individualized prescription of oral supplements may assist in healing and DFUs prevention. ...
Article
Diabetic foot ulcers (DFUs) are common complications of diabetes mellitus that affect patients' quality of life and pose a burden on the healthcare system. Although malnutrition and specific nutritional deficiencies can seriously impact wound healing in patients with chronic nonhealing wounds, the role of nutrition in the prevention and management of DFUs is still not clear. This review discusses the significance of frequent diet assessment and nutritional education of patients with DFUs with individualized correction of deficiencies and emphasis on adequate protein intake along with correction of vitamins D, C, E, and selenium status. Future research should clarify the impact of nutritional interventions, potentially involving the use of probiotics, zinc, and omega-3 fatty acids, and successfully translating the findings into practical guidelines for use in everyday clinical practice.
... Worldwide, the number of diabetic foot infections (DFIs) is increasing exponentially [1,2]. Several publications have found an inverse association between relevant signs of malnutrition and the capacity to heal diabetic foot ulcers (DFUs) [4,5]. These publications suggest there is a positive correlation between DFU healing and selected nutritional interventions [4,5]. ...
... Several publications have found an inverse association between relevant signs of malnutrition and the capacity to heal diabetic foot ulcers (DFUs) [4,5]. These publications suggest there is a positive correlation between DFU healing and selected nutritional interventions [4,5]. Likewise, our clinical experience suggests a worse outcome for many diabetic foot problems in patients with malnutrition and better outcomes when nutritional interventions are provided, at least for the postoperative period. ...
... This aspect is very important in the literature. Many published data support a role of nutrition in wound closure in patients with a diabetic foot ulcer (DFU) [4,5]. Nutrition is believed to be favorably connected in almost every facet of healing of DFUs, including immune function, glycemic control, hydroxyproline concentrations, weight management, and physical ability [4,5]. ...
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Aim: While a patient's nutritional status is known to generally have a role in postoperative wound healing, there is little information on its role as therapy in the multifaceted problem of diabetic foot infections (DFIs). Methods: We assessed this issue by conducting a retrospective case-control cohort study using a multivariate Cox regression model. The nutrition status of the DFI patients was assessed by professional nutritionists, who also orchestrated the nutritional intervention (counselling, composition of the intrahospital food) during hospitalization. Results: Among 1,013 DFI episodes in 586 patients (median age 67 years; 882 with osteomyelitis), 191 (19%) received a professional assessment of their nutrition accompanied by between 1 and 6 nutritional interventions. DFI cases who had professional nutritionists' interventions had a significantly shorter hospital stay, had shorter antibiotic therapies, and tended to fewer surgical debridements. By multivariate analysis, episodes with low Nutritional Risk Status- (NRS-) Scores 1-3 were associated with significantly lower failure rates after therapy for DFI (Cox regression analysis; hazard ratio 0.2, 95% confidence interval 0.1-0.7). Conclusions: In this retrospective cohort study, DFI episodes with low NRS-Score were associated with lower rates of clinical failure after DFI treatment, while nutritional interventions improved the outcome of DFI. We need prospective interventional trials for this treatment, and these are underway.
... HMB/Arg/Gln is given as a supplement in the daily nutritional regimen for the healing of recalcitrant wounds. Examples of such wounds include pressure ulcers (PUs) in patients in general hospitals [3], wounds experienced by patients who are diabetic [4][5][6], burn injuries [7], and patients in intensive care units [8]. ...
... Among the possible explanations for the additional benefit pro- vided by HMB/Arg/Gln in the healing of PUs in the current study are improved nitrogen balance, not necessarily due to a reduction in the rate of protein metabolism [29]; promotion of collagen production [9], including among patients who are diabetic [6]; and improvements in hematological parameters [30], protein balance [7], vascular endothelial function [12], and inflammation [31]. It must be emphasized that, at the start of the follow-up period, no differences were detected between the study subgroups with respect to matching indices (age, sex, main diagnoses, baseline area, and PU perimeter) or other indices (e.g., prevalence of participants who had been on PMV and DM prevalence). ...
Article
Background: Growing evidence suggests that beta-hydroxy-beta-methylbutyrate (HMB), arginine (Arg), and glutamine (Gln) positively affect wound recovery. This study investigated the effects of long-term administration of HMB/Arg/Gln on pressure ulcer (PU) healing in sedentary older adults admitted to geriatric and rehabilitation care facilities. Methods: This was a pilot retrospective case (standard of care and HMB/Arg/Gln)-control (standard of care alone) clinical study. Outcome measures were relative healing rates and Pressure Ulcer Scale for Healing (PUSH) scores (calculated after 4, 8, 12, 16, and 20 weeks) and time to healing. Results: The study subpopulation was comprised of 14 participants (four males, 28.6%) with the median age of 85.5 years (interquartile range [IQR], 82.0-90.2 years). The control subpopulation was comprised of 31 participants (18 males, 58.1%) with the median age of 84.0 years (IQR, 78.0-90.0 years). At the beginning of follow-up, there were no statistically significant demographic (sex and age) and clinical (main diagnosis, baseline area, and PU perimeter) differences between the groups. During the study period, there were no significant differences in the relative healing rates and PUSH scores between the subpopulations. The median time to complete healing in the study and control populations was 170.0 days (95% confidence interval [CI], 85.7-254.3) and 218.0 days (95% CI, 149.2-286.7) (log-rank, chi-square=3.99; p<0.046), respectively. Conclusion: More than 20 weeks of HMB/Arg/Gln supplementation had a positive effect on difficult PU healing in older adults with multiple comorbidities.
... In addition, the potential for pharmacological intervention to inhibit glycation processes or enhance AGE degradation offers a promising avenue for mitigating the progression of diabetes-related complications. Future research should focus on identifying and testing compounds that could counteract collagen stiffening and preserve tissue elasticity and function (Jones et al., 2014). Finally, extending this research to human studies would be invaluable. ...
Article
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The interplay between diabetes mellitus and the structural integrity of collagen has significant implications for tissue functionality and disease progression. The aim of this study was to empirically investigate the effects of ribose-induced glycation on the biomechanical properties of collagen fibrils, using atomic force microscopy for precise measurements. Methodology. We used collagen fibrils from the common digital extensor (CDE) and superficial digital flexor (SDF) tendons of an adult bovine model to mimic the glycation processes that occur in diabetic pathology. The samples underwent controlled glycation by incubation with ribose for 24 hours and 14 days compared to phosphate buffered saline treated controls. A Bioscope Catalyst atomic force microscope (Bruker, USA) was used for all atomic force microscopy imaging in this study. Scientific novelty. Our results show a marked increase in the elastic modulus of collagen fibrils after ribose treatment, indicating stiffening with glycation. Notably, SDF fibrils showed a greater increase in stiffness after 24 hours of ribose exposure compared to CDE fibrils, suggesting variations in glycation rates relative to fibril anatomy. Statistical analyses confirmed the significance of these findings and provided a model for understanding similar processes in human diabetes. Conclusions. The different response to glycation observed between CDE and SDF fibrils prompts further investigation into the role of anatomical and structural factors in glycation susceptibility. Identification of tissues at higher risk of glycation-induced damage could lead to the development of targeted prevention strategies for diabetic complications. In addition, the potential for pharmacological intervention to inhibit glycation processes or enhance advanced glycation end products (AGEs) degradation offers a promising avenue for mitigating the progression of diabetes-related complications. The results of this study highlight the potential of ribose-induced changes in collagen as a model for diabetes-related tissue changes and propose a mechanistic framework that could guide the development of interventions aimed at mitigating the effects of collagen-related diabetic complications.
... One case-control study investigated the correlation between Hcy levels and diabetic foot ulcers in type 2 diabetic patients, who were grouped according to the presence of PAD or neuropathy, and showed that low Hcy levels predicted the development of VDF ulcers (Gazzaruso et al. 2012). A prospective triple-blind trial investigating supplementation with arginine, glutamine and beta-hydroxy-betamethylbutyric acid (HMB) for the treatment of diabetic foot ulcers found that hydroxyproline concentrations were significantly higher in the treatment group after supplementation, suggesting that amino acid supplementation may promote diabetic foot wound healing (Jones et al. 2014). Homocysteine has also been associated with diabetic foot, and studies have found that every 1 µmol increase in plasma Hcy levels is associated with a 10% increase in the risk of diabetic foot ulcers (Gonzalez et al. 2010). ...
Article
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Diabetes mellitus (DM) is a severe chronic diseases with a global prevalence of 9%, leading to poor health and high health care costs, and is a direct cause of millions of deaths each year. The rising epidemic of diabetes and its complications, such as retinal and peripheral nerve disease, is a huge burden globally. A better understanding of the molecular pathways involved in the development and progression of diabetes and its complications can facilitate individualized prevention and treatment. High diabetes mellitus incidence rate is caused mainly by lack of non-invasive and reliable methods for early diagnosis, such as plasma biomarkers. The incidence of diabetes and its complications in the world still grows so it is crucial to develop a new, faster, high specificity and more sensitive diagnostic technologies. With the advancement of analytical techniques, metabolomics can identify and quantify multiple biomarkers simultaneously in a high-throughput manner, and effective biomarkers can greatly improve the efficiency of diabetes and its complications. By providing information on potential metabolic pathways, metabolomics can further define the mechanisms underlying the progression of diabetes and its complications, help identify potential therapeutic targets, and improve the prevention and management of T2D and its complications. The application of amino acid metabolomics in epidemiological studies has identified new biomarkers of diabetes mellitus (DM) and its complications, such as branched-chain amino acids, phenylalanine and arginine metabolites. This study focused on the analysis of metabolic amino acid profiling as a method for identifying biomarkers for the detection and screening of diabetes and its complications. The results presented are all from recent studies, and in all cases analyzed, there were significant changes in the amino acid profile of patients in the experimental group compared to the control group. This study demonstrates the potential of amino acid profiles as a detection method for diabetes and its complications.
... Earthworm treated group (Figure 3 e, f) exhibited an normal hepatic parenchyma that appeared free from any detectable alterations. The current data agreed with Kawakami et al., who claimed that the composite powder containing earthworm (CEP) protected against diabetic complications by improving lipid metabolism and suppressing liver deterioration progression [63]. Deng et al. believed that the earthworm extract had potent antioxidant properties attributed to minimized liver damage [61]. ...
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Diabetes mellitus is an endocrine disorder that affects various body functions. Earthworms are oligochaete soil macroinvertebrates with intrinsic antimicrobial, anti-inflammatory, antioxidant, and chelating abilities. This study aimed to examine earthworm extract's potential to treat diabetes in rats. There were three primary groups of six male Wistar albino rats: the control, the diabetic, and the earthworm extract groups. Streptozotocin (60 mg/kg, i.p.) was used to cause type 1 diabetes mellitus. The control and diabetic groups received 1 ml of distilled water, while the earthworm group received the earthworm extract (45 mg/Kg body weight) daily for four weeks. The earthworm extract group showed a significant reduction in glucose, arginase, alkaline phosphatase, alanine aminotransaminase, aspartate aminotransferase, total cholesterol, triglycerides, low-density lipoprotein, creatinine, urea, uric acid, malondialdehyde, and nitric oxide levels. On the contrary, the earthworm extract caused a significant increase in insulin, glucose-6-phosphate dehydrogenase, total protein, albumin, high-density lipoprotein, follicle-stimulating hormone, luteinizing hormone, testosterone, reduced glutathione, glutathione S-transferases, and catalase levels. The histopathological investigation illustrated the regeneration of damaged pancreatic beta cells and a clear improvement in the hepatic, kidney, heart, and testis structures. This study indicated the efficacy of earthworm extract in improving the biochemical and histopathological changes in diabetic rats' organs. The therapeutic effect of earthworm extract against diabetic complications results from its hypoglycemic activity, antioxidant impact, and regeneration of damaged tissues.
... Jones et al conducted a prospective cohort study of 9 diabetic foot patients, and the treatment group showed a higher hydroxyproline concentration after supplementation with arginine, glutamine, and β-hydroxy-β-methylbutyric acid (HMB), and it was significantly higher than before and statistically significant. 57 Changes in these amino acids may become the evaluation criteria for the efficacy of diabetic foot treatment. In addition, microdialysis can provide the metabolite concentration differences, giving valuable information. ...
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Metabolomics is the analysis of numerous small molecules known as metabolites. Over the past few years, with the continuous development in metabolomics, it has been widely used in the detection, diagnosis, and treatment of diabetes and has demonstrated great benefits. At the same time, studies on diabetes and its complications have discovered the metabolic markers that are characteristic of diabetes. However, the pathogenesis of diabetes has yet to be clarified, as well as no complete cure. The mechanism of diabetes has not been completely elucidated, and its eradication treatment is not available. Thus, prevention of the onset of the disease and its treatment have become very important. In this review, we focused on the recent progress in the use of metabolites in diabetes and their complications, as well as understanding the impact of diabetes metabolites.
... Em doentes obesos com úlceras de perna a malnutrição pode estar presente em 20-30% dos indivíduos (36). Este estado catabólico está associado a uma diminuição de massa magra e uma provável depleção de aminoácidos a nível muscular e periférico, incluindo glutamina, arginina a hidroximetilbutirato (37). ...
... The investigations of the interrelations between the processes of diabetes development and the metabolism of connective tissue proteins (31) and amino acids (68) pave the way for further evaluation of the effective regulators of collagen biosynthesis in hyperglycemia among these low-molecular compounds. The targeted amino acid supplementation with arginine, glutamine, and betahydroxy-beta-methylbutyrate may improve the healing of diabetic foot wounds via increased collagen production as well (69). Amino acid-containing preparation like Diabetex, (patency# EP 0877617 A1) significantly improves the wound healing and collagen formation while it induces re-epithelialization and neovascularization of diabetic foot wounds, exhibiting a safe profile on liver and kidney function tests and a significant reduction in fasting blood sugar (70). ...
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This review summarizes information on interrelations between diabetes development and collagen metabolism and structure. The growing global problem of diabetes requires the search for new strategies of its complications correction. Among them collagen structure violations and/or its impaired metabolism most often lead to profound disability. Even after several decades of intense studies, pathophysiological mechanisms underlying collagen changes in diabetes mellitus are still not well clear. The main complication is that not only diabetes cause changes in collagen metabolism and structure. Collagens via some mechanisms also may regulate glucose homeostasis, both directly and indirectly. The author also presented the results of own studies on bone and skin type I collagen amino acid composition changes with diabetes. Deepening our understanding of collagen metabolism and diabetes interrelations allows us to optimize approaches to overcome the collagen-mediated consequences of this disease. Recently, it has been clearly demonstrated that use of only antidiabetic agents cannot fully correct such violations. Preparations on the base of flavonoids, collagens and amino acids could be considered as perspective directions in this area of drug development.
... A vastly explored method for improving malnourishment is supplementation with different amino acids, which is investigated in animal testing [61][62][63][64] as well as in (hospitalized) patients [65][66][67][68], for a range of different conditions such as cancer, cardiac disease, sepsis, and liver metabolism, but also for its possible beneficial effects on post-surgical infection development [69] and in orthopedic diseases [70]. ...
Article
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With the increasing incidence of fractures now, and in the future, the absolute number of bone-healing complications such as nonunion development will also increase. Next to fracture-dependent factors such as large bone loss volumes and inadequate stabilization, the nutritional state of these patients is a major influential factor for the fracture repair process. In this review, we will focus on the influence of protein/amino acid malnutrition and its influence on fracture healing. Mainly, the arginine-citrulline-nitric oxide metabolism is of importance since it can affect fracture healing via several precursors of collagen formation, and through nitric oxide synthases it has influences on the bio-molecular inflammatory responses and the local capillary growth and circulation.
... muscle damage, stress hormone or inflammatory response, and accelerate recovery (2)(3)(4)(5). Due to HMB positive impact on skeletal muscle there are many studies describing various medical uses (solo or in combination with other nutrients), starting from muscle wasting conditions, which will be analyzed partially in this review, through diabetic foot wounds (6) and pressure ulcers (7,8). There are also publications about possible uses of HMB in treatment of head and neck cancer patients for prevention of radiation dermatitis and mucosistis after chemoradiotheraphy (9,10). ...
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β-Hydroxy-β-methylbutyrate (HMB) is a leucine metabolite, naturally appearing in human body. Both leucine and HMB are believed to be potent protein synthesis enhancers in skeletal muscles. The current articles reviews and summarizes findings from original studies on the possible therapeutic role of HMB in elderly sarcopenia. HMB seems to be capable of not only preventing, but also reversing sarcopenia. Five main effects on skeletal muscles have been noted: 1) inhibition of protein breakdown and thus lower muscle degradation, 2) increased endoplasmic reticulum calcium release, 3) lower fat content in skeletal muscle, 4) increased oxygen metabolism, 5) stimulation of satellite cells and thus muscle regeneration. Therefore, HMB emerges as potentially useful agent in treating and preventing sarcopenia.
... Administration of a mixture of arginine, glutamine, and b-hydroxyb-methylbutyrate was also reported to decrease wound sizes at 10 and 14 d after injury (45). Administration of these same amino acids also increased hydroxyproline content in diabetic foot ulcers (46), but not in a basic science model of the same injury (47). Regardless, there is considerable variation in supplementation and wound outcomes and definitive studies are needed to determine whether or not glutamine could be used therapeutically, either alone or in combination with other amino acids, to facilitate wound healing in a clinical setting. ...
Article
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Wound healing is a complex process marked by highly coordinated immune fluxes into an area of tissue injury; these are required for re-establishment of normal tissue integrity. Along with this cascade of cellular players, wound healing also requires coordinated flux through a number of biochemical pathways, leading to synthesis of collagen and recycling or removal of damaged tissues. The availability of nutrients, especially amino acids, is critical for wound healing, and enteral supplementation has been intensely studied as a potential mechanism to augment wound healing-either by increasing tensile strength, decreasing healing time, or both. From a practical standpoint, although enteral nutrient supplementation may seem like a reasonable strategy to augment healing, a number of biochemical and physiologic barriers exist that limit this strategy. In this critical review, the physiology of enteral amino acid metabolism and supplementation and challenges therein are discussed in the context of splanchnic physiology and biochemistry. Additionally, a review of studies examining various methods of amino acid supplementation and the associated effects on wound outcomes are discussed.
... Por lo tanto, este estudio confirma que TOCH tiene un beneficio potencial en el tratamiento de las DFU. k)"Targeted amino acid supplementation in diabetic foot wounds: pilot data and a review of the literature" (Diciembre 2014) 17 : ...
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Background: Foot ulcers in people with diabetes are non-healing, or poorly healing, partial, or full-thickness wounds below the ankle. These ulcers are common, expensive to manage and cause significant morbidity and mortality. The presence of a wound has an impact on nutritional status because of the metabolic cost of repairing tissue damage, in addition to the nutrient losses via wound fluid. Nutritional interventions may improve wound healing of foot ulcers in people with diabetes. Objectives: To evaluate the effects of nutritional interventions on the healing of foot ulcers in people with diabetes. Search methods: In March 2020 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. Selection criteria: We included randomised controlled trials (RCTs) that evaluated the effect of nutritional interventions on the healing of foot ulcers in people with diabetes. Data collection and analysis: Two review authors, working independently, assessed included RCTs for their risk of bias and rated the certainty of evidence using GRADE methodology, using pre-determined inclusion and quality criteria. Main results: We identified nine RCTs (629 participants). Studies explored oral nutritional interventions as follows: a protein (20 g protein per 200 mL bottle), 1 kcal/mL ready-to-drink, nutritional supplement with added vitamins, minerals and trace elements; arginine, glutamine and β-hydroxy-β-methylbutyrate supplement; 220 mg zinc sulphate supplements; 250 mg magnesium oxide supplements; 1000 mg/day omega-3 fatty acid from flaxseed oil; 150,000 IU of vitamin D, versus 300,000 IU of vitamin D; 250 mg magnesium oxide plus 400 IU vitamin E and 50,000 IU vitamin D supplements. The comparator in eight studies was placebo, and in one study a different dose of vitamin D. Eight studies reported the primary outcome measure of ulcer healing; only two studies reported a measure of complete healing. Six further studies reported measures of change in ulcer dimension, these studies reported only individual parameters of ulcer dimensions (i.e. length, width and depth) and not change in ulcer volume. All of the evidence identified was very low certainty. We downgraded it for risks of bias, indirectness and imprecision. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, increases the proportion of ulcers healed at six months more than placebo (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.42 to 1.53). It is also uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement increases the proportion of ulcers healed at 16 weeks compared with placebo (RR 1.09, 95% CI 0.85 to 1.40). It is uncertain whether the following interventions change parameters of ulcer dimensions over time when compared with placebo; 220 mg zinc sulphate supplement containing 50 mg elemental zinc, 250 mg magnesium oxide supplement, 1000 mg/day omega-3 fatty acid from flaxseed oil supplement, magnesium and vitamin E co-supplementation and vitamin D supplementation. It is also uncertain whether 150,000 IU of vitamin D, impacts ulcer dimensions when compared with 300,000 IU of vitamin D. Two studies explored some of the secondary outcomes of interest for this review. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, reduces the number of deaths (RR 0.96, 95% CI 0.06 to 14.60) or amputations (RR 4.82, 95% CI 0.24 to 95.88) more than placebo. It is uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement increases health-related quality of life at 16 weeks more than placebo (MD -0.03, 95% CI -0.09 to 0.03). It is also uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement reduces the numbers of new ulcers (RR 1.04, 95% CI 0.71 to 1.51), or amputations (RR 0.66, 95% CI 0.16 to 2.69) more than placebo. None of the included studies reported the secondary outcomes cost of intervention, acceptability of the intervention (or satisfaction) with respect to patient comfort, length of patient hospital stay, surgical interventions, or osteomyelitis incidence. One study exploring the impact of arginine, glutamine and β-hydroxy-β-methylbutyrate supplement versus placebo did not report on any relevant outcomes. Authors' conclusions: Evidence for the impact of nutritional interventions on the healing of foot ulcers in people with diabetes compared with no nutritional supplementation, or compared with a different dose of nutritional supplementation, remains uncertain, with eight studies showing no clear benefit or harm. It is also uncertain whether there is a difference in rates of adverse events, amputation rate, development of new foot ulcers, or quality of life, between nutritional interventions and placebo. More research is needed to clarify the impact of nutritional interventions on the healing of foot ulcers in people with diabetes.
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β-Hydroxy β-methylbutyrate (HMB) is a diet supplement known for its positive impact on muscle anabolism, which makes it very popular among amateur sportsmen. Diet enriched with HMB leads to decreased proteolysis in muscle tissue, which is extremely important in the process of muscle regeneration after intensive training. As the number of possible implications of this molecule in medicine is still growing,the aim of this review was to find potential applications of HMB in women and their infants during pregnancy and perinatal period. The HMB usage during pregnancy or shortly after birth is connected with increased muscle anabolism in the infants. Many factors like mTOR signaling pathway, increased activity of GH/IGF-1 axis or elevated blood concentration of some amino acids may be responsible for this effect. Such activity might be potentially helpful for infants born with intrauterine growth retardation (IUGR). Improvement in quality and quantity of colostrum and milk, positive impact on bones and cartilages or immunostimulating effect and deceased enamel roughness, which potentially reduces the risk of caries, are other potential benefits. Although numerous possible positive effects have been postulated, there seems to be insufficient data on safety of long term HMB supplementation, especially in pregnancy and perinatal period. Moreover, there are studies that imply increased peripheral insulin resistanceafter prolonged supplementation of HMB. HMB usage can be beneficial in numerous health states, also in pregnancy and perinatal period, especially in infants with low birth weight or born preterm, but further investigation is needed to estimate benefits to risk ratio and introduce specific guidelines.
Chapter
The incidence of diabetes is increasing throughout the world. Ulcers affecting the lower limbs of diabetics are among the most frequent and costly clinical complications of the disease. Approximately $6–15 billion annually is spent on caring for all chronic wounds in the United States [1]. Among the diabetic population, approximately 1–4 % will develop a foot ulcer per year, with up to 25 % developing an ulcer during their lifetime. Many of these ulcers result in significant morbidity, leading to amputations, disfigurement, sepsis, and sometimes, even death.
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Background Diabetes is an important reason for end-stage renal failure and diabetic foot wounds worsen the life qualities of these patients. Protein and amino acid support accelerates the wound healing. The purpose of this retrospective study is to examine the effect of beta-hydroxy-beta-methylbutyrate, arginine and glutamine (Abound®) supplementation on the wound healing. Methods A total of 11 diabetic dialysis patients were included in this retrospective study aiming to evaluate the effect of the diet support with beta-hydroxy-beta-methylbutyrate, arginine and glutamine on wound healing in diabetic dialysis patients. Pre-treatment and post-treatment wound depth and wound appearance were scored in accordance with the “Bates-Jensen” wound assessment tool. The results of 4-week treatment with beta-hydroxy-beta-methylbutyrate, arginine and glutamine (Abound®) support were evaluated in terms of wound healing. Results The mean age of patients was 66 (SD: 10, range: 51-81) and 9 (81.8%) of them were males. After the 4-week treatment, in accordance with the Bates-Jensen scoring, healing was observed on the wound depth score of 7(63.6%) patients and on wound appearance score of 8(72.7%) patients out of 11. While the wound depth score of 4(36.4%) cases and wound appearance score of 3(27.3%) cases remained the same, no deterioration was observed on any cases throughout the follow-up period. Conclusion In conclusion, our findings revealed that Abound treatment makes a positive contribution to the wound healing in diabetic dialysis patients.
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Purpose: We aimed to evaluate the effects of β-hydroxy-β-methylbutyrate, L-glutamine, and L-arginine (HMB/Glu/Arg) on radiation-induced acute inflammation and mucosal atrophy in the oral mucosa. Methods: Twenty-eight rats were divided into four groups. group (G) 1 was defined as control group, and G2 was the radiation therapy (RT) group. G3 and G4 were HMB/Glu/Arg control and 17 Gy RT plus HMB/Glu/Arg groups, respectively. A single dose of 17 Gy RT was given to the head and neck area, and the active supplement consisting of 5.2 g of HMB, 29.6 g arginine, and 29.6 g of glutamine which was equivalent to 60 kg adult dose was calculated for each rat and administrated orally. HMB/Glu/Arg started from the day of RT and continued until the animals were sacrificed 7 days after the RT. The extent of acute inflammation and mucosal atrophy for each rat was quantified with image analysis of histological sections of the oral mucosa. Results: There were significant differences in terms of epithelial thickness, subepithelial edema, inflammation, and congestion between all groups (p values were <0.001, 0.003, <0.001, and 0.001 for each parameter, respectively). Using HMB/Glu/Arg alone led to hypertrophic changes in the epithelial layer. Moreover, when used with RT, HMB/Glu/Arg reversed radiation-induced epithelial atrophy (p, 0.006) and decreased radiation-induced inflammation at a significant level (p, 0.007). Conclusion: Concomitant use of HMB/Glu/Arg appears to ameliorate the radiation-induced acute inflammation and mucosal atrophy which represent the early phase of acute oral mucositis; however, this finding should be clarified with further clinical studies.
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Chronic ulcers are a growing cause of patient morbidity and contribute significantly to the cost of health care in the United States. The most common etiologies of chronic ulcers include venous leg ulcers (VLUs), pressure ulcers (PrUs), diabetic neuropathic foot ulcers (DFUs), and leg ulcers of arterial insufficiency. Chronic wounds account for an estimated 6to6 to 15 billion annually in US health care costs; however, it is difficult to get accurate measurements on this, because these patients are often seen in a variety of settings or simply fail to access the health care system.
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In 2007, the treatment of diabetes and its complications in the United States generated at least $116 billion in direct costs; at least 33% of these costs were linked to the treatment of foot ulcers. Although the team approach to diabetic foot problems is effective in preventing lower extremity amputations, the costs associated with implementing a diabetic foot care team are not well understood. An analysis of these costs provides the basis for this report. Diabetic foot problems impose a major economic burden, and costs increase disproportionately to the severity of the condition. Compared with diabetic patients without foot ulcers, the cost of care for patients with a foot ulcer is 5.4 times higher in the year after the first ulcer episode and 2.8 times higher in the second year. Costs for the treatment of the highest-grade ulcers are 8 times higher than for treating low-grade ulcers. Patients with diabetic foot ulcers require more frequent emergency department visits, are more commonly admitted to hospital, and require longer length of stays. Implementation of the team approach to manage diabetic foot ulcers within a given region or health care system has been reported to reduce long-term amputation rates from 82% to 62%. Limb salvage efforts may include aggressive therapy, such as revascularization procedures and advanced wound healing modalities. Although these procedures are costly, the team approach gradually leads to improved screening and prevention programs and earlier interventions, and thus seems to reduce long-term costs. To date, aggressive limb preservation management for patients with diabetic foot ulcers has not usually been paired with adequate reimbursement. It is essential to direct efforts in patient-caregiver education to allow early recognition and management of all diabetic foot problems and to build integrated pathways of care that facilitate timely access to limb salvage procedures. Increasing evidence suggests that the costs for implementing diabetic foot teams can be offset over the long-term by improved access to care and reductions in foot complications and in amputation rates.
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In 2007, the treatment of diabetes and its complications in the United States generated at least $116 billion in direct costs; at least 33% of these costs were linked to the treatment of foot ulcers. Although the team approach to diabetic foot problems is effective in preventing lower-extremity amputations, the costs associated with implementing a diabetic-foot–care team are not well understood. An analysis of these costs provides the basis for this report. Diabetic foot problems impose a major economic burden, and costs increase disproportionately to the severity of the condition. Compared with diabetic patients without foot ulcers, the cost of care for those with foot ulcers is 5.4 times higher in the year after the first ulcer episode and 2.8 times higher in the second year. Costs for treating the highest-grade ulcers are 8 times higher than are those for treating low-grade ulcers. Patients with diabetic foot ulcers require more frequent emergency department visits and are more commonly admitted to the hospital, requiring longer lengths of stay. Implementation of the team approach to manage diabetic foot ulcers in a given region or health-care system has been reported to reduce long-term amputation rates 62% to 82%. Limb salvage efforts may include aggressive therapy such as revascularization procedures and advanced wound-healing modalities. Although these procedures are costly, the team approach gradually leads to improved screening and prevention programs and earlier interventions and, thus, seems to reduce long-term costs. To date, aggressive limb preservation management for patients with diabetic foot ulcers has not usually been paired with adequate reimbursement. It is essential to direct efforts in patient-caregiver education to allow early recognition and management of all diabetic foot problems and to build integrated pathways of care that facilitate timely access to limb salvage procedures. Increasing evidence suggests that the costs of implementing diabetic foot teams can be offset in the long term by improved access to care and reductions in foot complications and amputation rates. (J Am Podiatr Med Assoc 100(5): 335–341, 2010)
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To investigate the effect of L-arginine on endothelial function, transcutaneous oxygen and clinical neuropathy in patients with peripheral neuropathy as a result of diabetes. Thirty diabetic patients with peripheral neuropathy were randomized to receive L-arginine (3 g three times daily) or placebo (3 g three times daily) for 3 months. All patients had foot microcirculation and foot transcutaneous oxygen pressure (TcPO(2)), neuropathy disability score (NDS) and vibration perception threshold (VPT) assessed at baseline and follow-up. No difference was observed in endothelium-dependent and -independent vasodilation, TcPO(2), NDS and VPT. L-arginine has no effect on endothelial dysfunction, TcPO(2) and clinical neuropathy.
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The objective of this study was to characterize health care costs associated with diabetic lower-extremity ulcers. Adult patients with diabetes who had a lower-extremity ulcer episode during 2000 and 2001 were identified using claims data. Ulcer-related direct health care costs were computed for each episode. Episodes were stratified according to severity level based on the Wagner classification. A total of 2,253 patients were identified. The mean age was 68.9 years, and 59% of the patients were male. The average episode duration was 87.3 +/- 82.8 days. Total ulcer-related costs averaged 13,179 dollars per episode and increased with severity level, ranging from 1,892 dollars (level 1) to 27,721 dollars (level 4/5). Inpatient hospital charges accounted for 77% (10,188 dollars) of the overall cost, indicating that hospitalization was a major cost driver. Total ulcer-related costs were significantly higher for patients <65 years of age compared with those of older patients (16,390 dollars vs. 11,925 dollars, P = 0.02) and for patients with inadequate vascular status compared with patients with adequate vascular status (23,372 dollars vs. 5,218 dollars, P < 0.0001). Patients who progressed to a higher severity level also had significantly higher ulcer-related costs compared with patients who did not progress (20,136 dollars vs. 3,063 dollars, P < 0.0001). The high costs of treating diabetic lower-extremity ulcers emphasize the value of intensive outpatient interventions designed to prevent ulcer progression.