Background Diabetic foot ulcers portend an almost twofold increase in all-cause mortality compared with diabetes on its own. Aim To investigate the association between diabetic foot ulcers and risk of death. Methods We performed a meta-analysis of all observational studies investigating the association between diabetic foot ulcers and all-cause mortality. Risk ratios and risk differences were pooled in a random-effects model. The I 2 statistic was used to quantify heterogeneity between studies.Results Altogether, we identified 11 studies that reported 84 131 deaths from any cause in 446 916 participants with diabetes during a total of 643 499 person-years of follow-up. The crude event rate for all-cause mortality in individuals with diabetes who did not develop foot ulceration was 22% lower at 181.5 deaths (per 1000 person-years) than in those who developed foot ulcers (230.8 per 1000 person-years). Diabetic foot ulceration was associated with an increased risk of all-cause mortality (pooled relative risk 2.45, 95% CI 1.85-2.85). We did not observe any tangible differences in risk of all-cause mortality from diagnosis in studies reporting a mean duration of follow-up of ≤3 years (relative risk 2.43, 95% CI 2.27-2.61) or >3 years (relative risk 2.26, 95% CI 2.13-2.40) years. Funnel plot inspection revealed no significant publication bias among studies included in this meta-analysis. ConclusionsOur study shows an excess rate of all-cause mortality in people with diabetic foot ulceration when compared to those without foot ulceration. It is imperative that early interventions to prevent foot ulceration and modify cardiovascular disease risk factors are put in place to reduce excess mortality.

Aims/hypothesis The aim of this study was to determine whether social deprivation in the presence of diabetes is an independent predictor of developing a foot ulcer and separately of mortality. Methods This was a primary-care-based retrospective analysis of 13,955 adults with type 1 (n = 1370) or type 2 (n = 12,585) diabetes after a median follow-up of 10.5 years. Demographic characteristics, indices of social deprivation and clinical variables were assessed at baseline. The primary outcomes were new foot ulceration (in those without a previous history of foot ulcers) and all-cause mortality. Cox proportional hazard models were used to describe the associations among foot ulceration, social deprivation and mortality. Results The mean age of the population was 69.4 (range: 16-89) years. The incidence of foot ulceration was greater in individuals with type 2 (8.6%) compared with type 1 diabetes (4.8%). Occurrence was similar by sex, but increased with age and deprivation index. Individuals in the highest quintile of deprivation were 77% more likely to develop a foot ulcer compared with those in the lowest quintile (OR 1.77 [95% CI 1.45, 2.14], p < 0.0001). Overall, 2946 (21.1%) deaths were recorded. Compared with individuals without a foot ulcer, the development of a foot ulcer was associated with a higher age-and sex-adjusted mortality rate (25.9% vs 14.0%), and a 72% (HR Conclusions/interpretation This study confirms the high mortality rate in individuals with diabetes-related foot ulcers. In addition, socioeconomic disadvantage was found to be an independent effect modifier, contributing to an increased burden of mortality in people with diabetes who develop foot ulceration. In light of this, and as diabetes service configurations are orientated for the next 5-10 years, modelling of foot ulceration risk needs to take socioeconomic disadvantage into account.

ObjectiveTo identify clinical and biochemical characteristics associated with 7- &amp; 30-day mortality and intensive care admission amongst diabetes patients admitted with COVID-19.Research Design and MethodsWe conducted a cohort study collecting data from medical notes of hospitalised people with diabetes and COVID-19 in 7 hospitals within the Mersey-Cheshire region from 1 January to 30 June 2020. We also explored the impact on inpatient diabetes team resources. Univariate and multivariate logistic regression analyses were performed and optimised by splitting the dataset into a training, test, and validation sets, developing a robust predictive model for the primary outcome.ResultsWe analyzed data from 1004 diabetes patients (mean age 74.1 (± 12.6) years, predominantly men 60.7%). 45% belonged to the most deprived population quintile in the UK. Median BMI was 27.6 (IQR 23.9-32.4) kg/m2. The primary outcome (7-day mortality) occurred in 24%, increasing to 33% by day 30. Approximately one in ten patients required insulin infusion (9.8%). In univariate analyses, patients with type 2 diabetes had a higher risk of 7-day mortality [p &lt; 0.05, OR 2.52 (1.06, 5.98)]. Patients requiring insulin infusion had a lower risk of death [p = 0.02, OR 0.5 (0.28, 0.9)]. CKD in younger patients (&lt;70 years) had a greater risk of death [OR 2.74 (1.31-5.76)]. BMI, microvascular and macrovascular complications, HbA1c, and random non-fasting blood glucose on admission were not associated with mortality. On multivariate analysis, CRP and age remained associated with the primary outcome [OR 3.44 (2.17, 5.44)] allowing for a validated predictive model for death by day 7.ConclusionsHigher CRP and advanced age were associated with and predictive of death by day 7. However, BMI, presence of diabetes complications, and glycaemic control were not. A high proportion of these patients required insulin infusion warranting increased input from the inpatient diabetes teams.

Objective: To identify clinical and biochemical characteristics associated with 7-& 30day mortality and intensive care admission amongst diabetes patients admitted with COVID-19.Research Design and Methods: We conducted a cohort study collecting data from medical notes of hospitalised people with diabetes and COVID-19 in 7 hospitals within the Mersey-Cheshire region from 1 January to 30 June 2020. We also explored the impact on inpatient diabetes team resources. Univariate and multivariate logistic regression analyses were performed and optimised by splitting the dataset into a training, test, and validation sets, developing a robust predictive model for the primary outcome. Results:We analyzed data from 1004 diabetes patients (mean age 74.1 (± 12.6) years, predominantly men 60.7%). 45% belonged to the most deprived population quintile in the UK. Median BMI was 27.6 (IQR 23.9-32.4) kg/m 2 . The primary outcome (7-day mortality) occurred in 24%, increasing to 33% by day 30. Approximately one in ten patients required insulin infusion (9.8%). In univariate analyses, patients with type 2 diabetes had a higher risk of 7-day mortality [p < 0.05, OR 2.52 (1.06, 5.98)]. Patients requiring insulin infusion had a lower risk of death [p = 0.02, OR 0.5 (0.28, 0.9)]. CKD in younger patients

Methods Anaesthetised C57BL6 mice were given an intratracheal 20 mg dose of lipopolysaccharide (LPS). Mice were sacrificed at various time points, their lungs were removed, immersed in a buffer to fix and permeabilise cells, and a single cell suspension was produced by mechanical disruption. After incubation at 378C the cell suspension was washed and centrifuged. Samples were stained at room temperature in the dark with antibodies to identify alveolar macrophages (AM) and epithelial cells (AEC), and to measure the intracellular levels of active phosphorylated forms of ERK, p38 and MK2. Finally the cells were washed and resuspended for flow cytometric analysis. Results AM showed a rapid increase in levels of phosphorylated MK2 (see Abstract P251 Figure 1) as well as p38 and ERK on stimulation by intraalveolar LPS. As MK2 showed the most robust response, we determined its phosphorylation in AEC. Those AEC expressing low levels of surface ICAM-1 (likely type II pneumocytes) showed a pattern of increased MK-2 phosphorylation, while ICAM-1 high expressing AEC (type I pneumocytes) did not show a clear response to LPS stimulation. Conclusion We have developed a method of investigating activation of individual cells within the lung using flow cytometry, in terms of intracellular MAPkinase phosphorylation. Our data show that AM are rapidly activated upon stimulation by intraalveolar LPS, whereas AEC show signs of delayed activation with type II pneumocytes more responsive than type I cells. Applying this technique to other models, in which alternative cell types and/or pathways may be involved, will enhance our understanding of cellular activation and interactions during acute lung injury.