Negative pressure wound therapy in the treatment of diabetic foot ulcers may be mediated through differential gene expression.

AIMS: Negative pressure wound therapy (NPWT) has been successfully used as a treatment for diabetic foot ulceration (DFU). Its mechanism of action on the molecular level, however, is not fully understood. We assessed the effect of NPWT on gene expression in patients with type 2 diabetes (T2DM) and DFU. METHODS: We included two cohorts of patients-individuals treated with either NPWT or standard therapy. The assignment to NWPT was non-randomized and based on wound characteristics. Differential gene expression profiling was performed using Illumina gene expression arrays and R Bioconductor pipelines based on the 'limma' package. RESULTS: The final cohort encompassed 21 patients treated with NPWT and 8 with standard therapy. The groups were similar in terms of age (69.0 versus 67.5 years) and duration of T2DM (14.5 versus 14.4 years). We identified four genes differentially expressed between the two study arms post-treatment, but not pre-treatment: GFRA2 (GDNF family receptor alpha-2), C1QBP (complement C1q binding protein), RAB35 (member of RAS oncogene family) and SYNJ1 (synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1). Interestingly, all four genes seemed to be functionally involved in wound healing by influencing re-epithelialization and angiogenesis. Subsequently, we utilized co-expression analysis in publicly available RNA-seq data to reveal the molecular functions of GFRA2 and C1QBP, which appeared to be through direct protein-protein interactions. CONCLUSIONS: We found initial evidence that the NPWT effect on DFUs may be mediated through differential gene expression. A discovery of the specific molecular mechanisms of NPWT is potentially valuable for its clinical application and development of new therapies.

Negative-pressure wound therapy for management of chronic neuropathic noninfected diabetic foot ulcerations - short-term efficacy and long-term outcomes.

PURPOSE: Negative 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. METHODS: Based 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. RESULTS: Patients 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). CONCLUSIONS: NPWT 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.

Osteoprotegerin gene polymorphism in diabetic Charcot neuroarthropathy.

AIMS: Recently, an association between two polymorphisms (1181G>C and 245T>G) of the osteoprotegerin (OPG) gene and diabetic Charcot neuroarthropathy was suggested on the basis of studies of a limited number of samples derived from subjects from one geographical region (Italy). The aim of this study was to assess the presence of various osteoprotegerin gene polymorphisms in patients with diabetes and Charcot neuroarthropathy compared with subjects with diabetic neuropathy but no Charcot foot and healthy controls from another geographical region (Poland). METHODS: DNA was isolated from 54 patients with Charcot neuroarthropathy, 35 subjects with diabetic neuropathy but no Charcot foot, and 95 healthy controls to evaluate OPG gene polymorphisms and their possible contribution to the development of Charcot neuroarthropathy. RESULTS: Statistically significant differences between the group of subjects with neuropathy but no Charcot neuroarthropathy and the control group were found for 1217C>T, 950T>C and 245T>G polymorphisms, between the group of patients with Charcot neuroarthropathy and the control group for 1181G>C and 950T>C polymorphisms, and between the group of subjects with neuropathy but no Charcot neuroarthropathy and the group of patients with Charcot neuroarthropathy for 1217C>T and 245T>G polymorphisms. CONCLUSION: We suggest that genetic factors, particularly OPG gene polymorphisms, may play a role in the development of diabetic Charcot neuroarthropathy.

Intensive glucose therapy and clinical implications of recent data: a consensus statement from the Global Task Force on Glycaemic Control.

BACKGROUND: There is compelling evidence showing that achieving good glycaemic control reduces the risk of microvascular complications in people with type 1 and type 2 diabetes. Likewise, there is clear evidence to show that achieving good glycaemic control reduces the risk of macrovascular complications in type 1 diabetes. The UKPDS 10-year follow up suggests that good glycaemic control also reduces the risk of macrovascular complications in type 2 diabetes. Despite this, recent results from ACCORD, ADVANCE and VADT present conflicting results and data from the ACCORD trial appear to suggest that very low HbA(1c) targets (<6.0%) may, in fact, be dangerous in certain patient populations. AIM: To review recent results from ACCORD, ADVANCE and VADT and provide clear guidance on the clinical significance of the new data and their implications for the practising physician treating patients with type 2 diabetes. METHODS: A Pubmed search was used to identify major randomised clinical trials examining the association between glycaemic control and diabetes-associated complications. The data was reviewed and discussed by the GTF through a consensus meeting. The recommendations for clinical practice in this statement are the conclusions of these analyses and discussions. RESULTS: Evidence from ACCORD, ADVANCE, VADT and UKPDS suggests that certain patient populations, such as those with moderate diabetes duration and/or no pre-existing CVD, may benefit from intensive blood glucose control. These trials highlight the benefit of a multifactorial treatment approach to diabetes. However, ACCORD results indicate that aggressive HbA(1c) targets (<6.0%) may not be beneficial in patients with existing CVD and a longer duration of diabetes. CONCLUSIONS: Glycaemic control remains a very important component of treatment for type 2 diabetes and contrasting results from the ACCORD, ADVANCE and VADT should not discourage physicians from controlling blood glucose levels.

The effect of insulin and sulodexide (Vessel Due F) on diabetic foot syndrome: pilot study in elderly patients.

OBJECTIVE: To assess the efficacy of insulin plus sulodexide (a mixture of 80% heparin-like substances and 20% dermatan sulphate) on diabetic ulcers, and its influence on foot skin microcirculation and diabetic neuropathy. RESEARCH DESIGN AND METHODS: Two groups of diabetic patients, suffering from severe neuropathy and ulceration, were randomly assigned to insulin (I) plus sulodexide (S) (n=12) or insulin plus placebo (P) (n=6) therapy, for 10 weeks. Laser Doppler assessment of foot skin flow (LDF), at rest and 30 or 60 s after arterial occlusion, and nerve conduction tests (sensorial evoked and motoric conduction potentials) have been evaluated in both groups. RESULTS: Postischaemic flow was 2.5 times shorter in ulcerated vs. non-ulcerated feet in diabetic patients. A significant increase in flows after 30 and 60 s ischaemia was detected in both groups at the end of therapy (IS group, ulcerated foot, LDF=60 s: from 99.1+/-14.3 to 218.6+/-28.6 PU, P<.001. IP group=from 110.5+/-13.0 to 164.8+/-15.4 PU, P<.05). The length of reactive hyperaemia was higher in IS vs. IP group (IS: from 30.3+/-2.9 to 43.9+/-2.2 s, P<.001; IP: from 28.7+/-3.0 to 33.3+/-3.3 s, ns). Ninety-two percent of ulcers heals in a mean time of 46.4 days (IS group) vs. 83% and 63.0 days, respectively, in IP group. Nerve conduction studies have not demonstrated within- and between-group differences. CONCLUSIONS: Sulodexide and insulin improve the postischaemic skin flow in ulcerated feet, without affecting nerve conduction tests. The effect of sulodexide results additive to insulin; it is clinically relevant, in the view of the possibility of reducing the time needed to completely heal ulcers. The ultimate validation of these preliminary results requires extensive trials.

[Diabetic foot syndrome in clinical practice. I. A model of a Diabetic Foot Consulting Unit]. / Zesp57ol stopy cukrzycowej w praktyce klinicznej. I. Model Gabinetu Stopy Cukrzycowej.

Complex pathogenesis of the foot syndrome involving a number of body system and tissues provided us with grounds for making multispecialistic assessment of its severity. Also a decision about the type and intensity of procedure should be multispecialistic. An interdisciplinary team consists of a diabetologist, diabetic educator, podiatrist, kinesitherapist, orthopedist, general and vascular surgeon and a consultant from manufacturing corrective shoes. The make-up of the team implies that the procedure includes education, metabolic normalization of diabetes mellitus, orthopedic correction, possible surgical intervention and rehabilitation. Results discussed in part II of the study indicate the effectiveness of such approach.

[Diabetic foot syndrome in clinical practice. II. Results after one year at the Diabetic Foot Consulting Unit]. / Zespól stopy cukrzycowej w praktyce klinicznej II. Wyniki rocznej dzialalnosci Gabinetu Stopy Cukrzycowej.

The study included 46 patients with the diabetic foot syndrome and ulcerations, and 40 patients with high-risk foot. Mean duration of hospitalization of the patients with ulcerations was 54 days, mean daily glycemia decreased from 162.5 mg% to 114.9 mg%. Ulcerations were completely healed in 93.5% of patients, whereas high and partial foot amputation was high and 3.2% of patients, respectively. The annual amputation rate was 2.3% in the entire group of diabetic foot patients (86). The present results indicate the necessity for adoption of a multidisciplinary approach to the problem of diabetic foot. It may be added that cooperation in glycemia normalization and patients education may decrease the number of amputations, and hence the degree of physical disability in diabetic foot patients.

[Evaluation of the practical use of the Becton-Dickinson (B-D) insulin pen injector]. / Ocena praktycznego zastosowania injektora piórowego Becton-Dickinson (B-D).

UNLABELLED: The aim of this study was to assess insulin pen-injector in respect to: 1) improvement of metabolic control of diabetic patients, 2) improvement quality of life as well as complications connected with the use of pen patients. 23 IDDM and 7 NIDDM patients were enrolled to the study. Monthly check-up, control of diabetic complications, biochemical tests and glycemic profile and level of HbA1 c were performed. Human insulin containers of Eli Lilly-were used with the pens. Each month the glycemic profile and after 3 months HbA1c were tested. Special questionnaire was used to gather patients comments and remarks on the use of pens. RESULTS: 1. After 3 months of the pen use the mean levels of glucose were lower as well as the level of HbA1c. 2. Patients found the pens as easy and convenient way of insulin use, impairing their comfort of life. The moment of initiation of B-D pen injector was combined with the intensive insulin therapy, application of human insulin and both education and self-control. The assessment of the one only parameter among the others is hardly possible nevertheless it should be stressed that in intensive conventional insulin therapy, insulin pen injector was found as practical element improving treatment regimen.

[Cholesterol and phospholipid levels in erythrocyte membrane of patients with blood lipid disorders and hypertension]. / Stezenie cholesterolu i fosfolipidów w blonie komórkowej erytrocytów u osób z dyslipidemia i nadcisnieniem.

The aim of this paper was search for possible relationship between cholesterol and phospholipids in erythrocyte++ membrane and pathological entities i.e. hypertension and dyslipidemia. Both are the main risk factors of atherosclerosis and in both condition disturbances at the cell membrane level were detected. 124 persons (both men and women in a age group 20-59), employees of industrial enterprise were included into study. Standard questionnaire was performed as well as body weight and height, blood pressure, biochemical tests-lipids, cell membrane lipids serum and intracellular electrocytes as well as 24 h electrolyte urine excretion. The following findings were reported: cell membrane cholesterol concentration correlates with sex, age, body weight, systolic and diastolic blood pressure and triglycerydes HDL-cholesterol and serum phospholipids. The biggest influence on cholesterol concentration in cell membrane have the following factors: sex, age and serum triglycerides. The most important finding was that the lipid metabolism disturbances has impact on triglyceride elevation in serum and that arterial hypertension is connected with decreased cholesterol concentration in erytrocyte membrane.