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- Andersson, Christian X, 1973, et al.
(author)
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Inflamed adipose tissue, insulin resistance and vascular injury
- 2008
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In: Diabetes/Metabolism Research and Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:8, s. 595-603
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Journal article (peer-reviewed)abstract
- Type 2 diabetes is the most common metabolic disorder today and has reached epidemic proportions in many countries. Insulin resistance and inflammation play a central role in the pathogenesis of type 2 diabetes and are present long before the onset of the disease. During this time, many of the complications associated with type 2 diabetes are initiated. Of major concern is the two- to fourfold increase in cardiovascular morbidity and mortality in this group compared to a nondiabetic population. Obesity, characterized by enlarged fat cells, and insulin resistance are, like type 2 diabetes, associated with impaired adipogenesis and a low-grade chronic inflammation that to a large extent emanates from the adipose tissue. Both these processes contribute to unfavourable alterations of the circulating levels of several bioactive molecules (adipokines) that are secreted from the adipose tissue, many of which have documented inhibitory effects on insulin sensitivity in the liver and peripheral tissues and, in addition, have negative effects on the cardiovascular system.Here we review current knowledge of the adipose tissue as an endocrine organ, the local and systemic effects of a chronic state of low-grade inflammation residing in the adipose tissue, and, in particular, the effects of inflammation and circulating adipokines on the vascular wall.
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| 2. |
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| 3. |
- Apelqvist, Jan, et al.
(author)
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The development of global consensus guidelines on the management of the diabetic foot
- 2008
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In: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:S1, s. 116-118
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Journal article (peer-reviewed)abstract
- The future for diabetes is grave. Now described as the global epidemic of the 21st century, the increasing incidence of diabetes (in 2007 over 246 million people affected by diabetes) will place considerable strain on resources and will bring suffering to many if the preventative measures promoted by the International Diabetes Federation (IDF), the International Working Group on the Diabetic Foot (IWGDF) and other diabetes representative organizations are not put into effect. Ulcers of the foot in diabetes are a source of major suffering and cost. Investing in a diabetic foot care guideline can be one of the most cost-effective forms of healthcare expenditure, provided the guideline is goal-focused and properly implemented. The objective of the IWGDF, founded in 1996, is to develop guidelines that will reduce the impact of diabetic foot disease through cost-effective and quality healthcare, based on the principles of evidence-based medicine. Three IWGDF working groups were invited to write specific consensus guidelines on different subjects, according to the current standards of evidence based medicine. Therefore, for the first time, new 2007 texts were produced according to a systematic review of the literature, in order to inform protocols for routine care and to highlight areas which should be considered for further study. After reaching worldwide consensus, the review reports and specific guidelines were launched in May 2007.
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| 4. |
- Apelqvist, Jan
(author)
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The foot in perspective.
- 2008
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In: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:1, s. 110-115
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Journal article (peer-reviewed)abstract
- The diabetic foot constitutes a tremendous challenge for patients, caregivers and the health care system. The International Consensus Document of 1999 was a milestone in the recognition of the importance and consequences of the diabetic foot. Since then, many original papers have been published in this area.Large cohort studies have given us a deeper understanding regarding factors related to the outcome of diabetic foot ulcers: according to these studies, the severity of diabetic foot ulcers is greater than previously reported. More than 50% of individuals' foot ulcers have signs of infection at admission, and one-third have signs of both peripheral artery disease (PAD) and infection. The co-morbidities increase significantly with increasing severity of the foot disease. However, the trend in all these studies is a successive improvement in healing rate (50-60% at 20 weeks follow-up, > 75% at 1 year). It is important to differentiate between neuropathic and neuro-ischaemic ulcers with regard to factors related to outcome and co-morbidities.Recent research has emphasized the importance of psychological factors in the development and outcome of diabetic foot ulcers. Studies have shown that perceptions of the individual's own risks based on symptoms, and their own beliefs in the efficacy of self-care, can affect foot-care practice.The importance and influence of the health care organization and reimbursement should not be underestimated, both in the prevention and management of diabetic foot lesions. The diabetic foot should be considered a lifelong condition, as having had one ulcer dramatically increases the risk of developing a new ulcer.In an individual with diabetes and a foot ulcer, the ulcer should be considered as a sign of multi-organ disease, and a holistic approach to both management and prevention is recommended. Copyright (c) 2008 John Wiley & Sons, Ltd.
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| 5. |
- Berendt, A R, et al.
(author)
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Diabetic foot osteomyetitis: a progress report on diagnosis and a systematic review of treatment
- 2008
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In: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:S1, s. 145-161
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Research review (peer-reviewed)abstract
- The International Working Group on the Diabetic Foot appointed an expert panel to provide evidence-based guidance on the management of osteomyelitis in the diabetic foot. Initially, the panel formulated a consensus scheme for the diagnosis of diabetic foot osteomyelitis (DFO) for research purposes, and undertook a systematic review of the evidence relating to treatment. The consensus diagnostic scheme was based on expert opinion; the systematic review was based on a search for reports of the effectiveness of treatment for DFO published prior to December 2006. The panel reached consensus on a proposed scheme that assesses the probability of DFO, based on clinical findings and the results of imaging and laboratory investigations. The literature review identified 1168 papers, 19 of which fulfilled criteria for detailed data extraction. No significant differences in outcome were associated with any particular treatment strategy. There was no evidence that surgical debridement of the infected bone is routinely necessary. Culture and sensitivity of isolates from bone biopsy may assist in selecting properly targeted antibiotic regimens, but empirical regimens should include agents active against staphylococci, administered either intravenously or orally (with a highly bioavailable agent). There are no data to support the superiority of any particular route of delivery of systemic antibiotics or to inform the optimal duration of antibiotic therapy. No available evidence supports the use of any adjunctive therapies, such as hyperbaric oxygen, granulocyte-colony stimulating factor or larvae. We have proposed a scheme for diagnosing DFO for research purposes. Data to inform treatment choices in DFO are limited and further research is, urgently needed.
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| 6. |
- Berendt, A R, et al.
(author)
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Specific guidelines for treatment of diabetic foot osteomyelitis
- 2008
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In: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:S1, s. 190-191
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Journal article (peer-reviewed)abstract
- This article is based upon "The management of diabetic foot osteomyelitis - a progress report on diagnosing and a consensus on treating osteomyelitis". The principle of treatment is to administer antibiotics while providing a local environment in which the medication can work. This typically involves the removal of dead, soft tissue and accessible dead bone during the wound care process. These interventions may be undertaken by any appropriately trained health care provider.
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| 7. |
- Burén, Jonas, et al.
(author)
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Is insulin resistance caused by defects in insulin's target cells or by a stressed mind?
- 2005
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In: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 21:6, s. 487-494
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Journal article (other academic/artistic)abstract
- The importance of understanding insulin action is emphasized by the increasing prevalence of insulin resistance in various populations and by the fact that it plays an important pathophysiological role in many common disorders, for example, diabetes, obesity, hypertension and dyslipidemia. The primary factors responsible for the development of insulin resistance are so far unknown, although both genetic and environmental factors are involved. The genetic defects responsible for the common forms of insulin resistance, for example, in type 2 diabetes, are largely unidentified. Some studies from our group as well as by other investigators suggest that cellular insulin resistance is reversible and that it may be secondary to factors in the in vivo environment. These may include insulin-antagonistic action of hormones like catecholamines, glucocorticoids, sex steroids and adipokines as well as dysregulation of autonomic nervous activity and they could contribute to the early development of insulin resistance. Some of these factors can directly impair glucose uptake capacity and this might be due to alterations in key proteins involved in insulin's intracellular signaling pathways. This article briefly summarizes proposed mechanisms behind cellular and whole-body insulin resistance. In particular, we question the role of intrinsic defects in insulin's target cells as primary mechanisms in the development of insulin resistance in type 2 diabetes and we suggest that metabolic and neurohormonal factors instead are the main culprits.
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| 8. |
- Eneroth, Magnus, et al.
(author)
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The value of debridement and Vacuum-Assisted Closure (V.A.C.) Therapy in diabetic foot ulcers.
- 2008
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In: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:S1, s. 76-80
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Journal article (peer-reviewed)abstract
- BACKGROUND: Treatment of diabetic foot ulcers includes a number of different regimes such as glycaemic control, re-vascularization, surgical, local wound treatment, offloading and other non-surgical treatments. Although considered the standard of care, the scientific evidence behind the various debridements used is scarce. This presentation will focus on debridement and V.A.C. Therapy, two treatments widely used in patients with diabetes and foot ulcers. METHODS: A review of existing literature on these treatments in diabetic foot ulcers, with focus on description of the various types of debridements used, the principles behind negative pressure wound therapy (NPWT) using the V.A.C. Therapy system and level of evidence. RESULTS: Five randomized controlled trials (RCT) of debridement were identified; three assessed the effectiveness of a hydrogel as a debridement method, one evaluated surgical debridement and one evaluated larval therapy. Pooling the three hydrogel RCTs suggested that hydrogels are significantly more effective than gauze or standard care in healing diabetic foot ulcers. Surgical debridement and larval therapy showed no significant benefit. Other debridement methods such as enzyme preparations or polysaccharide beads have not been evaluated in RCTs of people with diabetes. More than 300 articles have been published on negative pressure wound therapy, including several small RCTs and a larger multi-centre RCT of diabetic foot ulcers. Negative pressure wound therapy seems to be a safe and effective treatment for complex diabetic foot wounds, and could lead to a higher proportion of healed wounds, faster healing rates, and potentially fewer re-amputations than standard care. CONCLUSIONS: Although debridement of the ulcer is considered a prerequisite for healing of diabetic foot ulcers, the grade of evidence is quite low. This may be due to a lack of studies rather than lack of effect. Negative pressure wound therapy seems to be safe and effective in the treatment of some diabetic foot ulcers, although there is still only one well-performed trial that evaluates the effect. Copyright (c) 2008 John Wiley & Sons, Ltd.
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| 9. |
- Fritz, Tomas, et al.
(author)
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Low-intensity exercise increases skeletal muscle protein expression of PPARdelta and UCP3 in type 2 diabetic patients
- 2006
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In: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 22:6, s. 492-498
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Journal article (peer-reviewed)abstract
- BACKGROUND: Physical exercise provides health benefits for people with type 2 diabetes mellitus, partly by enhancing skeletal muscle insulin action. We tested the hypothesis that changes in expression of key genes in skeletal muscles relate to exercise-induced improvements in type 2 diabetic patients. METHODS: We determined mRNA expression of 20 selected genes following a self-supervised program of walking (> 150 min per week) over a 4-month period. RESULTS: This level of physical activity improved clinical parameters in approximately half the participants, as determined by reduced hypertension and enhanced insulin sensitivity (defined by reduced plasma-insulin levels and improved homeostasis model assessment (HOMA)). Skeletal muscle mRNA expression of Cbl-associated protein (CAP), diacylglycerol kinase (DGK)delta, uncoupling protein (UCP) 3, nuclear respiratory factor (NRF)-1, and peroxisome proliferator-activated receptor (PPAR)delta tended to increase in type 2 diabetic patients with an improved clinical profile. Skeletal muscle protein expression of PPARdelta and UCP3 was increased significantly after physical exercise in patients with an improved clinical profile, but were unchanged in patients who did not show exercise-mediated improvements in clinical parameters. CONCLUSIONS: This study provides clinical evidence that improvements in insulin sensitivity can be achieved in type 2 diabetic patients after individually executed low-intensity exercise training. Moreover, the positive clinical response to exercise is correlated with changes in skeletal muscle proteins involved in the regulation of mitochondrial biogenesis and metabolism. These changes in skeletal muscle gene expression offer a possible molecular explanation for the improvements in clinical outcomes.
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