Presence of chronic diabetic foot ulcers is associated with more frequent and more advanced retinopathy.

AIMS: To clarify the frequency and severity of diabetic retinopathy in a group of people with Type 2 diabetes and chronic diabetic foot ulcers, and to compare visual acuity, levels of retinopathy and clinical significant macular oedema with a matched control group of people with Type 2 diabetes without a history of chronic diabetic foot ulcers. METHODS: Visual acuity and fundus imaging were evaluated in 90 white people with at least 3 months' duration of full-thickness diabetic foot ulcers below the ankle and the results compared with those in 180 white people with Type 2 diabetes without a history of chronic diabetic foot ulcers (control group). Controls were matched for age, sex and duration of diabetes. RESULTS: Despite similar age and diabetes duration, severe non-proliferative or proliferative diabetic retinopathy was present in 41% of the people in the diabetic foot ulcer group as compared to 15% in the control group (P<0.001). Only 6% in the diabetic foot ulcer group was without any diabetic retinopathy as compared to 34% among controls. Proliferative diabetic retinopathy was more common in the diabetic foot ulcer group (31% vs 8%; P<0.001), but time-to-proliferative diabetic retinopathy did not differ between groups. Clinically significant macular oedema was more frequently present, and the diabetic foot ulcer group exhibited significantly worse results in best and worst eye visual acuity testing. CONCLUSIONS: In this northern European setting almost all people with Type 2 diabetes and chronic diabetic foot ulcers had diabetic retinopathy. Almost one-third had proliferative diabetic retinopathy as compared to <10% in our matched control group. More advanced diabetic retinopathy was linked to worse visual acuity.

Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a systematic review.

The outcome of management of diabetic foot ulcers remains a challenge, and there remains continuing uncertainty concerning optimal approaches to management. It is for these reasons that in 2008 and 2012, the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing published systematic reviews of the evidence to inform protocols for routine care and to highlight areas, which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between June 2010 and June 2014. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound and other systemic therapies, which did not fit in the aforementioned categories. Heterogeneity of studies prevented pooled analysis of results. Of the 2161 papers identified, 30 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic reviews, and the conclusion is similar: that with the possible exception of negative pressure wound therapy in post-operative wounds, there is little published evidence to justify the use of newer therapies. Analysis of the evidence continues to present difficulties in this field as controlled studies remain few and the majority continue to be of poor methodological quality.

Heart rate-corrected QT interval prolongation as a prognostic marker for 3-year survival in people with Type 2 diabetes undergoing above-ankle amputation.

AIM: To evaluate whether heart rate-corrected QT interval is a plausible prognostic factor for survival after major amputation in people with Type 2 diabetes. METHODS: All people with Type 2 diabetes aged < 80 years who underwent a major amputation at two hospitals with multidisciplinary diabetic foot teams were evaluated and grouped according to whether their heart rate-corrected QT interval was  ≤  or  > 440 ms. RESULTS: A total of 70 patients with a median age of 72 years were included in the study. During the 3 years of follow-up, 38 patients (54%) died. Heart rate-corrected QT interval prolongation was present in 51.4% of the patients and was strongly associated with 3-year mortality (73 vs 36%; P < 0.001). In a Cox proportional hazard model, heart rate-corrected QT interval prolongation was the strongest independent risk factor for 3-year mortality [hazard ratio 2.20 (95% CI 1.11-4.38)]. Treatment with metformin seemed to have a protective effect [hazard ratio 0.22 (95% CI 0.05-0.94)]. CONCLUSIONS: The findings of the present study indicate that heart rate-corrected QT interval prolongation is associated with increased mortality in people with Type 2 diabetes undergoing above-ankle amputation.

Use of an autologous leucocyte and platelet-rich fibrin patch on hard-to-heal DFUs: a pilot study.

OBJECTIVE: Leucopatch is a leukocyte and platelet-rich fibrin patch that provides concentrated blood cells and signal substances to the surface of an ulcer. It is produced by centrifugation of the patient's own venous blood. The aim of this pilot multicentre cohort study was to evaluate effects of the leucocyte patch in patients with hard-to-heal diabetic foot ulcers (DFUs). METHOD: Non-ischaemic Wagner grade 1 or 2 DFUs with a duration of more than 6 weeks and a maximal area of 10cm² were included. Patients with >40% ulcer area change during a two-week run-in period were excluded. The treatment was applied once a week for up to 19 treatments or until the foot ulcer was completely epithelialised. The primary endpoint was healing within 20 weeks. RESULTS: Of the 60 patients who gave consent 16 were excluded during run-in period, 44 patients initiated study treatment and 39 were included in the per-protocol analysis. Complete epithelisation was achieved in 34% (per-protocol analysis 36%) at 12 weeks and 52% (59%) at 20 weeks. In patients with ulcer duration less than 6 months, 73% of ulcers healed within 20 weeks. Patients with healed ulcers had larger ulcer area reduction during the first two treatment weeks compared to non-healers. Adverse events were mild and rare. CONCLUSION: The leucocyte patch is well-tolerated, easy to use and has potential in the armamentarium of the DFU treatment, provided this outcome is confirmed in an appropriately powered randomised clinical trial.

The impact of metabolic control and QTc prolongation on all-cause mortality in patients with type 2 diabetes and foot ulcers.

AIMS/HYPOTHESIS: The increased all-cause mortality in patients with chronic diabetic foot ulcers cannot fully be explained by traditional cardiovascular risk factors. The significance of heart-rate-corrected QT (QTc) prolongation, a finding often seen in these patients, is unknown. Recently, the importance of metabolic control and hypoglycaemia has been discussed. The aim of this study was to evaluate the impact of different HbA1c levels and QTc prolongation on all-cause mortality in the high-risk population of patients with type 2 diabetes mellitus and foot ulcers. METHODS: All patients with type 2 diabetes, younger than 80 years, visiting our diabetes foot unit, with a foot ulcer duration >4 weeks, were screened for participation. Patients on dialysis were excluded. Patients were grouped according to HbA1c level and QTc time ≤ or > 440 ms. RESULTS: Patients (n = 214, median age 69.1 years) were grouped according to HbA1c level (HbA1c < 7.5% [<58 mmol/mol] n = 81, 7.5-8.9% [58-74 mmol/mol] n = 70, >8.9% [>74 mmol/mol] n = 63). Baseline characteristics, including use of potential hypoglycaemic drugs, were similar between groups. During the 8 years of follow-up 151 patients died (70.6%) and HbA1c < 7.5% (<58 mmol/mol) was strongly associated with increased mortality. The highest mortality was seen in patients with a combination of HbA1c < 7.5% (<58 mmol/mol) and QTc prolongation, with an 8 year mortality of 92.1% as compared with 48.8% in those with HbA1c < 7.5% (<58 mmol/mol) but without QTc prolongation. CONCLUSION/INTERPRETATIONS: HbA1c < 7.5% (<58 mmol/mol) in a high-risk population of patients with type 2 diabetes and foot ulcers is associated with a significantly higher mortality, particularly in patients with QTc prolongation.

The prevalence of atrial fibrillation in a geographically well-defined population in northern Sweden: implications for anticoagulation prophylaxis.

OBJECTIVES: The aims of this study were to evaluate the community-based prevalence of atrial fibrillation (AF) in a western society using a geographically well-defined population in the northern part of Sweden as a reference and to estimate the proportion of patients eligible for oral anticoagulation (OAC) prophylactic therapy according to the stroke risk indices CHADS2 and CHA2 DS2 -VASc. Bleeding risk was assessed using the HAS-BLED score. DESIGN: The study population was recruited from AURICULA, a Swedish national quality register for patients receiving anticoagulation treatment. All patients with the diagnosis AF in the catchment area are registered in AURICULA. RESULTS: Of the 65 532 inhabitants in the catchment area, 1616 were diagnosed with AF (1200 cases were characterized as chronic AF). Thus, the overall prevalence of AF was 2.5%. The prevalence increased with age from 6.3% in patients over 55 years of age to 13.8% in those over 80 years. The prevalence was higher in men than in women in all age groups. Overall, 56.3% and 85.1% of the population were at high risk of stroke (≥2 points) according to CHADS2 and CHA2 DS2 -VASc, respectively. In addition, 26.9% had an increased bleeding risk according to HAS-BLED. CONCLUSION: Within this large Caucasian population, we identified the highest community-based prevalence of AF to date. The prevalence was strongly associated with increasing age and male gender. Using CHA2 DS2 -VASc instead of CHADS(2) widened the indication for OAC prophylactic therapy of AF in this population.

A systematic review of interventions to enhance the healing of chronic ulcers of the foot in diabetes.

The outcome of management of diabetic foot ulcers is poor, and there is continuing uncertainty concerning optimal approaches to management. It was for these reasons that in 2006 the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing undertook a systematic review of the evidence to inform protocols for routine care and to highlight areas which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between December 2006 and June 2010. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae and hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; hyperbaric oxygen therapy (HBOT); compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound; other systemic therapies which did not fit in the above categories. Heterogeneity of studies prevented pooled analysis of results. Of the 1322 papers identified, 43 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic review, but the conclusion is similar: that with the exception of HBOT and, possibly, negative pressure wound therapy, there is little published evidence to justify the use of newer therapies. This echoes the conclusion of a recent Cochrane review and the systematic review undertaken by the National Institute for Health and Clinical Excellence Guidelines Committee in the UK. Analysis of evidence presents considerable difficulties in this field particularly as controlled studies are few and the majority are of poor methodological quality.

Relationship between ulcer healing after hyperbaric oxygen therapy and transcutaneous oximetry, toe blood pressure and ankle-brachial index in patients with diabetes and chronic foot ulcers.

AIMS/HYPOTHESIS: The randomised, double-blind, placebo-controlled Hyperbaric Oxygen Therapy (HBOT) in Diabetic Patients with Chronic Foot Ulcers (HODFU) study showed beneficial effect of HBOT. As this treatment is expensive and time-consuming, being able to select patients for therapy would be very useful. The aim of this study was to evaluate whether circulatory variables could help in predicting outcome of HBOT. METHODS: All HODFU study participants who completed therapy, predefined as receiving at least 36 out of 40 scheduled HBOT/placebo sessions, were included in this study (n = 75). Baseline transcutaneous oximetry (TcPO2), toe blood pressure (TBP) and ankle-brachial index (ABI) were measured. Ulcer healing rate was registered at the 9-month follow-up visit. An ulcer was considered healed when it was completely epithelialised and remained so at the 12-month follow-up. RESULTS: In the HBOT group TcPO2 were significantly lower for patients whose ulcer did not heal as compared with those whose ulcers healed. A significantly increased healing frequency was seen with increasing TcPO(2) levels in the HBOT group (TcPO2/healing rate: <25 mmHg/0%; 26-50 mmHg/50%; 51-75 mmHg/73%; and >75 mmHg/100%). No statistically significant relation between the level of TBP or ABI and healing frequency was seen. CONCLUSIONS/INTERPRETATION: Our results indicate that TcPO2 in contrast to ABI and TBP correlates to ulcer healing following HBOT. We suggest HBOT as a feasible adjunctive treatment modality in diabetic patients with chronic non-healing foot ulcers when basal TcPO2 at the dorsum of the foot is above 25 mmHg. TRIAL REGISTRATION: NCT00953186 FUNDING: Mrs Thelma Zoegas Foundation and Faculty of Medicine, Lund University.

Hyperbaric oxygen therapy improves health-related quality of life in patients with diabetes and chronic foot ulcer.

AIMS: Adjunctive treatment with hyperbaric oxygen therapy has recently been shown to improve ulcer healing in patients with chronic diabetic foot ulcer. The aim of the present study is to evaluate whether hyperbaric oxygen therapy improves the health related quality of life in these patients. METHODS: Prospective randomized placebo-controlled double-blinded study setting using SF-36. RESULTS: A total of 75 patients were included in the study; 38 were randomized to hyperbaric oxygen therapy and 37 to placebo (hyperbaric air). The overall mean physical and mental summary scores for the entire study population at baseline were 29.6 ± 8.8 and 47.5 ± 12.4, respectively. There was a significant difference between baseline and 1 year follow-up responses to the mental summary score and two of the eight (SF-36) (?) domains in the -hyperbaric oxygen group, whereas no significant improvement of health related quality of life was seen in the placebo group. Comparing quality of life in patients who healed their ulcer (healers) with those who did not (non-healers), post-treatment levels of the mental health summary score, social functioning and role limitations due to physical and emotional health were significantly improved in healers. No differences were seen in any SF-36 (?) domain in non-healers. CONCLUSIONS: Hyperbaric oxygen therapy improves long-term health related quality of life in patients with chronic diabetic foot ulcers, possibly attributable to better ulcer healing.

Complexity of factors related to outcome of neuropathic and neuroischaemic/ischaemic diabetic foot ulcers: a cohort study.

AIMS/HYPOTHESIS: We sought to identify factors related to short-term outcome of foot ulcers in patients with diabetes treated in a multidisciplinary system until healing was achieved. METHODS: Consecutively presenting patients with diabetes and worst foot ulcer (Wagner grade 1-5, below ankle) (n = 2,511) were prospectively followed and treated according to a standardised protocol until healing was achieved or until death. The number of patients lost to dropout was 31. The characteristics of the remaining 2,480 patients were: 1,465 men, age 68 +/- 15 years (range 18-96), type 1 diabetes 18%, type 2 diabetes 82% and insulin-treated 62%. RESULTS: The healing rate without major amputation in surviving patients was 90.6% (n = 1,867). Sixty-five per cent (n = 1,617) were healed primarily, 9% (n = 250) after minor amputation and 8% after major amputation; 17% (n = 420) died unhealed. Out of 2,060 surviving patients, 1,007 were neuroischaemic (48.8%). In a multiple regression analysis, primary healing was related to co-morbidity, duration of diabetes, extent of peripheral vascular disease and type of ulcer. In neuropathic ulcers, deep foot infection, site of ulcer and co-morbidity were related to amputation. Amputation in neuroischaemic ulcers was related to co-morbidity, peripheral vascular disease and type of ulcer. Age, sex, duration of diabetes, neuropathy, deformity and duration of ulcer or site of ulcer did not have an evident influence on probability of amputation. CONCLUSIONS/INTERPRETATION: Patients with diabetic foot ulcer suffer from multi-organ disease. Factors related to outcome are correspondingly complex.

Should snacks be recommended in obesity treatment? A 1-year randomized clinical trial.

OBJECTIVE: To study the effect to recommend no snacks vs three snacks per day on 1-year weight loss. The hypothesis was that it is easier to control energy intake and lose weight if snacks in between meals are omitted. SUBJECTS/METHOD: In total 140 patients (36 men, 104 women), aged 18-60 years and body mass index>30 kg/m(2) were randomized and 93 patients (27 men, 66 women) completed the study. A 1-year randomized intervention trial was conducted with two treatment arms with different eating frequencies; 3 meals/day (3M) or 3 meals and 3 snacks/day (3+3M). The patients received regular and individualized counseling by dieticians. Information on eating patterns, dietary intake, weight and metabolic variables was collected at baseline and after 1 year. RESULTS: Over 1 year the 3M group reported a decrease in the number of snacks whereas the 3+3M group reported an increase (-1.1 vs +0.4 snacks/day, respectively, P<0.0001). Both groups decreased energy intake and E% (energy percent) fat and increased E% protein and fiber intake but there was no differences between the groups. Both groups lost weight, but there was no significant difference in weight loss after 1 year of treatment (3M vs 3+3M=-4.1+/-6.1 vs -5.9+/-9.4 kg; P=0.31). Changes in metabolic variables did not differ between the groups, except for high-density lipoprotein that increased in the 3M group but not in 3+3M group (P<0.033 for group difference). CONCLUSION: Recommending snacks or not between meals does not influence 1-year weight loss.

Is chronic diabetic foot ulcer an indicator of cardiac disease?

OBJECTIVE: To evaluate presence and severity of cardiac disease in individuals with chronic diabetic foot ulcers using echocardiography. METHOD: Eighty consecutive patients with chronic foot ulcers attending the multidisciplinary diabetes foot clinic at Helsingborg Hospital underwent clinical examination, toe blood pressure measurement and a standard echocardiographic examination. RESULTS: Sixty-nine percent of the patients had a history of myocardial infarction and/or hypertension and/or heart failure; 78% had signs of left ventricular dysfunction and/or left ventricular hypertrophy and/or diastolic dysfunction; 76% of the patients without a history of cardiovascular disease had signs of cardiac dysfunction on echocardiography. CONCLUSION: Cardiac dysfunction is a common occurrence present in patients with chronic diabetic foot ulcers, even in those without known cardiac disease or hypertension. Echocardiography may be recommended as a screening procedure in the management of diabetic patients with chronic foot ulcers. The present study supports the view that diabetic chronic foot ulcers ought to be seen as a sign of cardiac disease, although further research is needed to elucidate this issue.

Transcutaneous oxygen pressure as a predictor for short-term survival in patients with type 2 diabetes and foot ulcers: a comparison with ankle-brachial index and toe blood pressure.

AIMS: Ankle-brachial index (ABI) is the most commonly used test when diagnosing peripheral vascular disease and is considered a marker for cardiovascular risk. Transcutaneous oxygen pressure (TcPO2), a test associated with microvascular function, has in several studies shown better correlation with diabetic foot ulcer (DFU) healing. Whether a low TcPO2 could be a marker for mortality in the high-risk population of DFU patients has not been evaluated before. The aim of this study was to evaluate the predictive value of TcPO2 in comparison with ABI and toe blood pressure (TBP) on 1-year mortality in type 2 diabetes patients with DFU. METHODS: Type 2 diabetes patients aged ≤ 90 years, with one DFU who attended our multidisciplinary DFU-unit during year 2013-2015 and were screened with TcPO2, ABI and TBP were retrospectively evaluated. One-year mortality was assessed from the national death register in Sweden. RESULTS: A total of 236 patients (30% women) with a median age of 76 (69-82) years were evaluated in this study. Within 1 year, 14.8% of the patients died. TcPO2 < 25 mmHg was associated with a higher 1-year mortality compared with TcPO2 ≥ 25 mmHg (27.7 vs. 11.6%, p = 0.003). TBP and ABI did not significantly influence 1-year mortality. In a Cox regression analysis adjusted for confounders, TcPO2 was independently predicting 1-year mortality with a hazard ratio for TcPO2 < 25 mmHg of 2.8 (95% CI 1.34-5.91, p = 0.006). CONCLUSIONS: This study indicates that a low TcPO2 is an independent prognostic marker for 1-year mortality among patients with type 2 diabetes and DFU.

A prospective study: hyperbaric oxygen therapy in diabetics with chronic foot ulcers.

Research suggests that hyperbaric oxygen therapy may have beneficial effects on ulcer healing and amputation rates in diabetic patients. This paper describes the design of a study that is evaluating its effects on chronic diabetic foot ulcers.

A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes.

The outcome of management of diabetic foot ulcers is poor and there is uncertainty concerning optimal approaches to management. We have undertaken a systematic review to identify interventions for which there is evidence of effectiveness. A search was made for reports of the effectiveness of interventions assessed in terms of healing, ulcer area or amputation in controlled clinical studies published prior to December 2006. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network (SIGN) criteria. Selected studies fell into the following categories: sharp debridement and larvae; antiseptics and dressings; chronic wound resection; hyperbaric oxygen (HBO); reduction of tissue oedema; skin grafts; electrical and magnetic stimulation and ultrasound. Heterogeneity of studies prevented pooled analysis of results. Of the 2251 papers identified, 60 were selected for grading following full text review. Some evidence was found to support hydrogels as desloughing agents and to suggest that a systemic (HBO) therapy may be effective. Topical negative pressure (TNP) may promote healing of post-operative wounds, and resection of neuropathic plantar ulcers may be beneficial. More information was needed to confirm the effectiveness and cost-effectiveness of these and other interventions. No data were found to justify the use of any other topically applied product or dressing, including those with antiseptic properties. Further evidence to substantiate the effect of interventions designed to enhance the healing of chronic ulcers is urgently needed. Until such evidence is available from robust trials, there is limited justification for the use of more expensive treatments and dressings.

Cardiovascular prevention before admission reduces mortality following acute myocardial infarction in patients with diabetes.

OBJECTIVES: Previous studies have shown that patients with diabetes mellitus have an increased mortality after suffering from acute myocardial infarction (AMI). Patients with diabetes have several risk factors for cardiovascular disease. Our objective was to quantify the prevalence of pharmacological cardiovascular prevention at admission and relate such treatment to short and long-term mortality following AMI in patients with and without diabetes. DESIGN AND SUBJECTS: All patients discharged from the Department of Internal Medicine at Helsingborg Hospital in 1996 and 1997 with a principal diagnosis of AMI were included in the study. Patients were divided into two groups according to the presence or absence of diabetes. Cardiovascular risk factors, on-going medication, type of ward following admission, peak creatine kinase MB mass (CKMB) and immediate treatment were registered. Information about death was obtained from the national register. Kaplan-Meier analysis was performed for life-expectancy. RESULTS: A total of 673 patients with AMI were registered, of which 117 (17.4%) had diabetes. No differences in 30 days (17.1% vs. 15.3%) or 1-year (24.8% vs. 27.4%) mortality were seen between the diabetes and control groups, whereas the 2-year mortality was significantly higher in the diabetes group (40.2% vs. 29.1%). Cardiovascular risk factors occurred more often in the diabetes group and the use of aspirin, ACE-inhibitors, statins and diuretics was significantly more frequent. In patients treated with aspirin, in combination with either statin or angiotensin converting enzyme (ACE)-inhibitor, or both, no differences were seen in 30 days, 1 or 2-year mortality between groups. CONCLUSION: In contrast to earlier studies we did not find an increased 30 days and 1-year mortality in patients with diabetes suffering from AMI. This discrepancy was linked to a higher frequency of pharmacological cardiovascular prevention, a finding supporting the hypothesis that survival of a diabetes patient after AMI could be affected by factors operating before the infarction.