Background Diabetes and its complications constitute a rising medical challenge. Special attention should be given to diabetic foot syndrome (DFS) due to its high rate of associated amputation and mortality. Negative pressure wound therapy (NPWT) is a frequently used supportive modality in a diabetic foot with ulcerations (DFUs). Design Here, we reviewed the current knowledge concerning the tissue and molecular mechanisms of NPWT action with an emphasis on diabetes research followed by a summary of clinical DFU studies and practice guidelines. Results Negative pressure wound therapy action results in two types of tissue deformations—macrodeformation, such as wound contraction, and microdeformation occurring at microscopic level. Both of them stimulate a wound healing cascade including tissue granulation promotion, vessel proliferation, neoangiogenesis, epithelialization and excess extracellular fluid removal. On the molecular level, NPWT results in an alteration towards more pro‐angiogenic and anti‐inflammatory conditions. It increases expression of several key growth factors, including vascular endothelial growth factor and fibroblast growth factor 2, while expression of inflammatory cytokinesis reduced. The NPWT application also alters the presence and function of matrix metalloproteinases. Clinical studies in DFU patients showed a superiority of NPWT over standard therapy in terms of efficacy outcomes, primarily wound healing and amputation rate, without a rise in adverse events. International guidelines point to NPWT as an important adjuvant therapy in DFU whose use is expected to increase. Conclusions This current knowledge improves our understanding of NPWT action and its tailoring for application in diabetic patients. It may inform the development of new treatments for DFU.
Background Type 2 diabetes mellitus (T2DM) is associated with a hypercoagulable state and increased neutrophil extracellular traps formation (NETosis). We investigated predictors of NETosis and cell death markers in circulating blood and their association with a prothrombotic state in T2DM. Methods In a cross-sectional study involving 113 T2DM patients aged 63.7 ± 8.2 years, we investigated citrullinated histone H3 (H3Cit), cell-free deoxyribonucleic acid (cfDNA), myeloperoxidase, neutrophil elastase, and inflammation markers, along with thrombin generation (TG), plasma clot lysis time (CLT), clot permeability (K s ) and fibrinolysis inhibitors. Results On multivariate logistic regression analysis adjusted for age and gender, predictors of high H3Cit (≥ 7.36 ng/mL, upper quartile) were: glycated hemoglobin (HbA1c) ≥ 7.0% and interleukin-6. Interleukin-6 was also found to be a predictor of high cfDNA (≥ 2.84 µg/mL, upper quartile) along with glucose. Citrullinated histone H3 and cfDNA correlated positively with CLT and inversely with K s , while TG associated solely with cfDNA. These associations were not seen with myeloperoxidase and neutrophil elastase. Patients with previous myocardial infarction (n = 21, 18.6%) had higher H3Cit (+108%, p < 0.001) and cfDNA (+45%, p = 0.022). On multivariable analysis adjusted for potential confounders, H3Cit and cfDNA, along with plasminogen activator inhibitor-1 and concomitant cardiovascular disease, were predictors of CLT. Citrullinated histone H3 alone was a predictor of K s and only cfDNA was a predictor of peak thrombin generated. Conclusions In T2DM, NETosis detectable in circulating blood is associated with inflammatory state and a prothrombotic state, especially hypofibrinolysis.
In this brief report, we describe the feat of four men with type 1 diabetes mellitus (T1DM) who decided to take part in a mountain ultramarathon in Bieszczady, Poland on May 27, 2016. Before participating in the competition, they asked two diabetologists for a consultation and to assist in diabetic control during the marathon. The aim of the study was to assess the metabolic safety in people with T1DM during extreme physical exertion in a mountain ultramarathon. All subjects were treated with continuous subcutaneous insulin infusion. The marathon route was 82 km, and the sum of the climbs and descents was 3235 and 3055 m, respectively. Diabetologists controlled glucose levels using a glucometer, plasma lactate levels, and ketones in the capillary blood. In addition, they monitored the intake of carbohydrates and fluids. Clinical tests were performed at the three checkpoints (at 32, 49, and 66 km) during the race and after completing the race (at 82 km). This study shows that extreme physical exertion by a person with type 1 diabetes is possible. All subjects avoided severe hypoglycemia by significantly reducing their insulin dose and consuming additional carbohydrates. Such actions, despite the occurrence of hyperglycemia >250 mg/dL did not result in ketoacidosis. Safe participation in mountain ultramarathons by people with type 1 diabetes can be achieved if they undertake appropriate physical and diabetologic preparation.
PurposeNegative pressure wound therapy (NPWT) is an adjunct method used in the treatment of diabetic foot ulceration (DFU). Real world data on its effectiveness and safety is scarce. In this prospective observational study, we assessed the short-term efficacy, safety, and long-term outcomes of NPWT in patients with type 2 diabetes (T2DM) and neuropathic, noninfected DFUs.MethodsBased on wound characteristics, mainly area (>1 vs. ≤1 cm2), 75 patients with DFUs treated in an outpatient clinic were assigned to NPWT (n = 53) or standard therapy (n = 22). Wound area reduction was evaluated after 8 ± 1 days. Long-term outcomes assessed included complete ulceration closure and recurrence rate.ResultsPatients assigned to NPWT were characterized by greater wound area (15.7 vs. 2.9 cm2). Reduction in wound area was found in both the NPWT (−1.1 cm2, −10.2%, p = 0.0001) and comparator group (−0.3 cm2, −18.0%, p = 0.0038). No serious adverse events related to NPWT were noted. Within 1 year, 55.1% (27/49) of DFUs were closed in the NPWT group and 73.7% (14/19) in the comparator group (p = 0.15). In the logistic regression, wound duration and smaller initial area, but not treatment mode, were associated with closure. One-year follow-up after DFU resolution revealed an ~30.0% recurrence rate in both groups (p = 0.88).ConclusionsNPWT is a safe treatment for neuropathic, nonischemic, and noninfected DFU in patients with T2DM, although this observational study did not prove its effectiveness over standard therapy. Additionally, we report a high rate of both closure and recurrence of ulcers, the latter irrespective of initial ulcer area.
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