Management of diabetic foot ulcers

Diabetic foot is a serious complication of diabetes which aggravates the patient's condition whilst also having significant socioeconomic impact. The aim of the present review is to summarize the causes and pathogenetic mechanisms leading to diabetic foot, and to focus on the management of this important health issue. Increasing physicians' awareness and hence their ability to identify the "foot at risk," along with proper foot care, may prevent diabetic foot ulceration and thus reduce the risk of amputation

Foot Muscle Energy Reserves in Diabetic Patients Without and With Clinical Peripheral Neuropathy

Objective: To investigate changes in the foot muscle energy reserves in diabetic non-neuropathic and neuropathic patients. Research Design and Methods: We measured the phosphocreatinine (PCr)/inorganic phosphate (Pi) ratio, total $^{31}$P concentration, and the lipid/water ratio in the muscles in the metatarsal head region using MRI spectroscopy in healthy control subjects and non-neuropathic and neuropathic diabetic patients. Results: The PCr/Pi ratio was higher in the control subjects (3.23 $\pm$ 0.43) followed by the non-neuropathic group (2.61 $\pm$ 0.36), whereas it was lowest in the neuropathic group (0.60 $\pm$ 1.02) (P < 0.0001). There were no differences in total $^{31}$P concentration and lipid/water ratio between the control and non-neuropathic groups, but both measurements were different in the neuropathic group (P < 0.0001). Conclusions: Resting foot muscle energy reserves are affected before the development of peripheral diabetic neuropathy and are associated with the endothelial dysfunction and inflammation

Wormholes and Ringholes in a Dark-Energy Universe

The effects that the present accelerating expansion of the universe has on the size and shape of Lorentzian wormholes and ringholes are considered. It is shown that, quite similarly to how it occurs for inflating wormholes, relative to the initial embedding-space coordinate system, whereas the shape of the considered holes is always preserved with time, their size is driven by the expansion to increase by a factor which is proportional to the scale factor of the universe. In the case that dark energy is phantom energy, which is not excluded by present constraints on the dark-energy equation of state, that size increase with time becomes quite more remarkable, and a rather speculative scenario is here presented where the big rip can be circumvented by future advanced civilizations by utilizing sufficiently grown up wormholes and ringholes as time machines that shortcut the big-rip singularity.Comment: 11 pages, RevTex, to appear in Phys. Rev.

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.</p> <p>Methods/Design</p> <p>This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.</p> <p>Discussion</p> <p>NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00980356</p

One step closer to understanding the role of bacteria in diabetic foot ulcers: characterising the microbiome of ulcers

Background: The aim of this study was to characterise the microbiome of new and recurrent diabetic foot ulcers using 16S amplicon sequencing (16S AS), allowing the identification of a wider range of bacterial species that may be important in the development of chronicity in these debilitating wounds. Twenty patients not receiving antibiotics for the past three months were selected, with swabs taken from each individual for culture and 16S AS. DNA was isolated using a combination of bead beating and kit extraction. Samples were sequenced on the Illumina Hiseq 2500 platform. Results: Conventional laboratory culture showed positive growth from only 55 % of the patients, whereas 16S AS was positive for 75 % of the patients (41 unique genera, representing 82 different operational taxonomic units (OTU’s). S. aureus was isolated in 72 % of culture-positive samples, whereas the most commonly detected bacteria in all ulcers were Peptoniphilusspp., Anaerococcus spp. and Corynebacterium spp., with the addition of Staphylococcus spp. in new ulcers. The majority of OTU’s residing in both new and recurrent ulcers (over 67 %) were identified as facultative or strict anaerobic Gram-positive organisms. Principal component analysis (PCA) showed no difference in clustering between the two groups (new and recurrent ulcers). Conclusions: The abundance of anaerobic bacteria has important implications for treatment as it suggests that the microbiome of each ulcer “starts afresh” and that, although diverse, are not distinctly different from one another with respect to new or recurrent ulcers. Therefore, when considering antibiotic therapy the duration of current ulceration may be a more important consideration than a history of healed ulcer

DPP4 inhibitors: From sitagliptin monotherapy to the new alogliptin-pioglitazone combination therapy

Diabetes mellitus (DM) is currently considered to be an epidemic disease. A safe and effective treatment has long been sought by scientists. Incretin mimetics and dipeptidyl peptidase-4 (DPP4) inhibitors represent a new class of agents that have recently been included as antidiabetic drugs. Although only a limited number of studies exist regarding the treatment of DM based on the incretin effect, DPP4 inhibitors have so far proved to be safe and effective, both when administered alone or in combination with other antidiabetic medication. This review focuses on incretin-effect physiology, as well as the DPP4 inhibitors, from sitagliptin to the new alogliptin-pioglitazone combination agent, given as monotherapy and in combination with other antidiabetic agents. © 2009 Springer Healthcare Communications

Clinical utility in the treatment of type 2 diabetes with the saxagliptin/metformin fixed combination

George S Panagoulias,1 John Doupis2,3 11st Department of Propaedeutic and Internal Medicine, Athens University Medical School, Laiko General Hospital, Athens, Greece; 2Salamis Naval Hospital, Athens, Greece; 3Diabetes Division, Iatriko Paleou Falirou Medical Center, Athens, Greece Abstract: Fixed-dose combination (FDC) products represent a widely accepted approach to type 2 diabetes treatment, given that monotherapies sometimes fail to meet the treatment targets &ndash; obtaining a sustained reduction in micro- and macrovascular complications. Saxagliptin (SAXA)/metformin (MET) FDC tablets can be used either alone or in combination with glyburide, thiazolidinediones, or insulin. It has been proven that the SAXA/MET combination leads to a significant improvement in glycemic control compared to placebo in patients with type 2 diabetes that is inadequately controlled with MET alone. In addition, this FDC has been proven to be safe for people with diabetes mellitus and established cardiovascular disease, elderly patients, and patients with impaired renal function (&gt;30 mL/minute), with dosage modification. Patient compliance, adherence, and persistence to the therapeutic regimen has been shown to be very good, while the titration of each compound according to the patient&#39;s profile is easy, given the availability of different formulations. The SAXA/MET FDC is a patient-friendly, dosage-flexible, and hypoglycemia-safe regimen with very few adverse events and a neutral or even favorable effect on body weight. It achieves significant glycosylated hemoglobin A1c reduction helping the patient to achieve his/her individual glycemic goals. Keywords: DPP-4 inhibitors, saxagliptin, metformin, fixed-dose combination products, FDC product