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Query: UMLS:C0011849 (diabetes)
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Diabetes is accompanied by delayed wound healing and insufficient granulation tissue formation, possibly because of a defect in fibroblast function. We have previously shown that fibroblasts derived from chronic diabetic foot ulcers have lower proliferation compared with those from uninjured skin. The aim of this study was to investigate possible mechanisms explaining the impaired fibroblast proliferation observed in fibroblasts from non-insulin-dependent diabetes mellitus chronic wounds and normal fibroblasts cultured in high glucose. Fibroblasts from two groups of patients were studied: nondiabetic patients with chronic venous stasis ulcers and non-insulin-dependent diabetes mellitus patients with chronic diabetic wounds. Biopsies from both uninjured skin and wounds were taken from the same patients to serve as sources of fibroblasts. A fluorometric method was used to determine DNA content, and a spectrophotometric lactate oxidase method was used for lactate level analysis. We found a dose-dependent inhibition of normal fibroblast proliferation when adding conditioned media from non-insulin-dependent diabetes mellitus wound fibroblasts. The conditioned medium, from these cells showed elevated l-lactate levels, 6.3 +/- 0.7 mmol/L, compared with media derived from nondiabetic, 2.1 +/- 0.3 mmol/L (p < 0.01), and diabetic uninjured skin fibroblasts, 3.5 +/- 0.6 mmol/L, and from chronic nondiabetic wound fibroblasts 2.9 +/- 0.3 mmol/L. Addition of 6 mmol/L l-lactate to uninjured normal fibroblasts resulted in decreased DNA content (58 +/- 7%, p < 0.01). Previously we have shown that high glucose concentrations inhibit fibroblast proliferation and induce growth factor resistance. When increasing the amount of d-glucose in the media, l-lactate levels increased in all cell types. When the uninjured normal cells were treated with beta-hydroxybutyrate, the total DNA content decreased by 42 +/- 5% (p < 0.05), with no significant increase in the l-lactate levels. These observations indicate that l-lactate production may be of importance for fibroblast proliferation in vitro and may play a role in fibroblast proliferation in vivo.
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PMID:Inhibited proliferation of fibroblasts derived from chronic diabetic wounds and normal dermal fibroblasts treated with high glucose is associated with increased formation of l-lactate. 977 56

Neuropathy and ischemia, two common complications of diabetes mellitus, are the primary underlying risk factors for the development of foot ulcers and their complications. The presence of symmetric distal polyneuropathy, encompassing motor, sensory, and autonomic involvement, is one of the most important factors in the development of diabetic foot ulcers. Perhaps one third of diabetic foot ulcers have a mixed neuropathic and ischemic etiology. Although neuropathy and ischemia are the primary predisposing factors in the formation of diabetic foot ulcers, an initiating factor, such as physical or mechanical stress, is required for an ulcer to develop. Ischemic ulcers develop as a result of low perfusion pressure in a foot with inadequate blood supply, whereas neuropathic ulcers result from higher pressures in a foot with adequate blood supply but loss of protective sensation. In addition to increasing the risk of ulceration, diabetes mellitus also increases the risk of infection by impairing the body's ability to eliminate bacteria. The processes by which ulcers develop are reviewed here.
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PMID:The development and complications of diabetic foot ulcers. 977 68

Research by our group and others indicates that many amputations of the lower limb occur after foot ulceration in patients with diabetes. It has been proposed that diabetic foot ulcers are mainly caused by repetitive trauma in areas of high plantar pressure during walking. Recent technology permits in-shoe measurement of plantar pressure. We assessed the reliability of the F-Scan in-shoe system for measurement of plantar pressure (Tekscan Inc., Boston, MA) in 51 subjects from a cohort of 977 diabetic veterans enrolled in a prospective study of risk factors for foot ulceration and amputation (the Seattle Diabetic Foot Study). Subjects were tested twice, wearing their own shoes. We used the coefficient of variation (CV) and the intra-class correlation coefficient (ICC) to estimate the reliability of F-Scan measurements of pressure. Peak pressure over the metatarsal heads proved to have the best indices of reliability, with CVs of 0.150 and 0.155, and ICCs of 0.755 and 0.751. Coefficients of variation for the heel, whole foot, and hallux ranged from 0.148 to 0.240, with ICCs ranging from 0.493 to 0.832. By published standards, peak pressures over the metatarsal heads and right hallux met the criteria for excellent reliability. Our ICCs for high pressures under the foot, heel, metatarsal heads, and hallux, and for peak pressures under the heel and left hallux represented fair-to-good reliability. No F-Scan plantar measurements could be judged by these criteria as having poor reliability. This clinical study found that for elderly patients with diabetes who were wearing their own shoes and were tested on two different days with different insoles, the F-Scan insole system was generally reliable for measurements of high pressure and peak pressure.
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PMID:Reliability of F-scan in-shoe measurements of plantar pressure. 980 Oct 80

A number of effective, low-cost strategies are available to identify and treat the person at risk for diabetic foot ulcers and lower-extremity amputation. These strategies must be more widely adopted by all diabetic care providers to maintain the integrity and function of the lower limb, and thus improve the quality of life for people with diabetes.
Diabetes Care 1998 Dec
PMID:Preventive foot care in people with diabetes. 983 12

The failure of foot wounds to heal results in 54,000 people with diabetes having to undergo extremity amputations annually. Therefore, treatment is needed to speed healing in people with diabetes in order to reduce the need for amputation. This study tested the effect of high-voltage pulsed current on foot blood flow in human beings who are at risk for diabetic foot ulcers. Neuropathy, vascular disease, Wagner Class, glucose, gender, ethnicity, and age were measured. A sample of 132 subjects was tested using a repeated-measures design. A baseline transcutaneous oxygen level was obtained; stimulation was applied, and transcutaneous oxygen measurements were recorded at 30- and 60- minute time intervals. The grouped foot transcutaneous oxygen levels decreased (F = 5.66, p =. 0039) following electrical stimulation. Analysis of variance (Scheffe, p <.05) showed that initial transcutaneous oxygen was significantly higher than subsequent readings. However, oxygen response was distributed bimodally: 35 (27%) subjects showed increased transcutaneous oxygen (mean 14.8 mm Hg), and 97 (73%) experienced a decreased transcutaneous oxygen reading (mean 12.2 mm Hg). Logistic regression analysis did not explain these differences. Although this treatment appears to increase blood flow in a subset of patients, further study is needed to identify probable mechanisms for this response.
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PMID:Effect of electrical stimulation on foot skin perfusion in persons with or at risk for diabetic foot ulcers. 984 63

Complications secondary to diabetes, such as diabetic foot ulcers, continue to be a major worldwide health problem. At the same time, health care systems are changing rapidly, causing concern about the quality of patient care. While the ultimate effect of current changes on health care professionals and patient outcomes remain uncertain, measures commonly used to reduce costs, e.g., disease and multi- disciplinary management strategies, have been shown to help prevent the occurrence of diabetic ulcers. In addition, utilizing a multi- disciplinary approach, the principles of off-loading and optimal wound care, the vast majority of diabetic foot ulcers can be expected to heal within 12 weeks of treatment. Education of primary care providers and patients is paramount.
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PMID:Diabetic foot ulcers: A framework for prevention and care. 1023 1

Pressure downloading (offloading) is the most important component in the prevention and treatment of diabetic foot ulcers because peripheral neuropathy is a major contributing factor to more than 90% of all diabetic foot ulcers. Downloading techniques range from the simplest insole, through many types of orthotics and footwear modifications including the ankle-foot orthosis and total contact casting, to surgical procedures. A philosophical difference exists between surgical and nonsurgical approaches, with the patient subjected to the bias of the practitioner. This article explores uniting both surgical and nonsurgical pressure downloading techniques, using a modified Carville Classification System to help the practitioner determine the appropriate method(s) of downloading. By adding a Category 4 to include diabetic persons with foot ulcers or acute Charcot events, a seamless system is obtained to categorize and treat all people with diabetes with pressure downloading recommendations.
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PMID:Downloading plantar foot pressures in the diabetic patient. 1068 50

Diabetic foot ulcers are frequent: 12,000 Dutch diabetes patients have such an ulcer. The ulcers have a multifactorial aetiology: polyneuropathy, biomechanical stress, infection, deficient footwear and to a less extent ischaemia are the major factors. The principles of ulcer treatment are relief of pressure, restoration of skin perfusion, treatment of infection, intensive wound care, metabolic control, treatment of comorbidity, and instruction of the patient. Wound healing is slow. The impaired wound healing is probably caused by deficiencies in local growth factors, changes in the extracellular matrix, diminished fibroblast function, decreased antimicrobial activity of leukocytes and disturbances in the macro- and microcirculation. In recent years several new treatment strategies have been developed to stimulate wound healing in diabetic foot ulcers. These (partly experimental) treatments include: topical growth factors, extracellular matrix products, bioengineered human skin, granulocyte colony stimulating factor and hyperbaric oxygen therapy. In particular recombinant human platelet derived growth factor (becaplermin) has proved to be clinically effective in chronic neuropathic foot ulcer and has been approved in the Netherlands.
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PMID:[New developments in the treatment of diabetic foot ulcers]. 1071 45

Wound healing, including re-epithelialization, is delayed in diabetes. Growth factors influence the healing process and amongst these, insulin-like growth factor (IGF) has been shown to stimulate keratinocyte proliferation in vitro. Monoclonal antibodies to insulin-like growth factors 1 and 2 (IGF1 and IGF2) were used to investigate their distribution in diabetic foot ulcers and surrounding tissues by immunohistochemistry, compared with diabetic and non-diabetic uninjured skin. IGF2 was found throughout the epidermis (stratum granulosum, spinosum, and basale) in all three groups. Staining for IGF2 was intense in both normal and diabetic skin as well as in diabetic foot ulcers, being greatest at the ulcer edge. IGF1, in comparison, was found throughout the epidermis of non-diabetic skin; expression was restricted to the stratum granulosum and spinosum of uninjured diabetic skin and was absent in the basal layer at the ulcer edge. A similar absence of IGF1 in dermal fibroblasts was found in tissue sections from diabetic patients. This lack of expression of IGF1 within the basal layer and fibroblasts may contribute to retarded wound healing in diabetes mellitus.
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PMID:Lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers. 1072 85

In the city of Wolfsburg, an annual screening to detect diabetic complications was introduced. In this model, project internists and general practitioners were remunerated for the documentation of diabetic complications. Ophthalmologists were remunerated for the documentation of screening for diabetic eye disease. The patients received a copy of the results. 1,563 patients (2.57% of 60,800 persons insured by the Volkswagen health insurance in the city) received ophthalmologic examination. 1,554 patients (2.6%) were examined by internists and general practitioners (58 practices). Out of 2,879 eyes examined in no retinopathy was detected 80.9%. In 14.1%, mild or moderate retinopathy was observed as well as 3.3% severe non-proliferative retinopathy and 1.3% proliferative retinopathy. 32 amputations were documented. Three of them were not related to diabetes. 32 patients had diabetic foot ulcers (75% males). The implementation of screening for diabetic complications was very successful. Based on the results, an evidence based disease management programme can be started focussing especially on improved tertiary prevention of diabetic complications.
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PMID:[Preventive care for early detection of diabetes mellitus complications: a model project in Wolfsburg]. 1093 54


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