Temporal trends in minor and major lower extremity amputation in people with type 2 diabetes: The Fremantle Diabetes Study.

AIMS: To determine whether incident minor and major lower extremity amputations (LEAs) have declined in recent decades in type 2 diabetes. METHODS: Participants with type 2 diabetes from the community-based Fremantle Diabetes Study Phases I (FDS1; n = 1,296, mean age 64.0 years, recruited 1993-1996) and II (FDS2; n = 1,509, mean age 65.4 years, recruited 2008-2011) were followed from entry to incident minor/major LEA, death or five years. Cox regression determined hazard ratios (HRs) for each outcome for FDS2 versus FDS1 and independent predictors of incident minor and major LEA in the combined cohort. RESULTS: Age- and sex-adjusted HRs (95% CIs) in FDS2 versus FDS1 for incident minor and major LEA were, respectively, 0.60 (0.27, 1.35) and 0.59 (0.22, 1.59). Higher glycated haemoglobin, urine albumin: creatinine (uACR) ratio and peripheral sensory neuropathy (PSN) were independent predictors of incident minor LEA. Higher fasting serum glucose, peripheral arterial disease (PAD), end-stage kidney disease and prior diabetes-related minor LEA were associated with incident major LEA. CONCLUSIONS: There were non-significant reductions of approximately 40% in incident minor and major LEA in community-based people with type 2 diabetes during the 15 years between FDS Phases. Predictors of minor/major LEA confirm distinct high-risk patient groups with implications for clinical management.

Wound healing with "spray-on" autologous skin grafting (ReCell) compared with standard care in patients with large diabetes-related foot wounds: an open-label randomised controlled trial.

There is an urgent need for interventions that improve healing time, prevent amputations and recurrent ulceration in patients with diabetes-related foot wounds. In this randomised, open-label trial, participants were randomised to receive an application of non-cultured autologous skin cells ("spray-on" skin; ReCell) or standard care interventions for large (>6 cm2 ), adequately vascularised wounds. The primary outcome was complete healing at 6 months, determined by assessors blinded to the intervention. Forty-nine eligible foot wounds in 45 participants were randomised. An evaluable primary outcome was available for all wounds. The median (interquartile range) wound area at baseline was 11.4 (8.8-17.6) cm2 . A total of 32 (65.3%) index wounds were completely healed at 6 months, including 16 of 24 (66.7%) in the spray-on skin group and 16 of 25 (64.0%) in the standard care group (unadjusted OR [95% CI]: 1.13 (0.35-3.65), P = .845). Lower body mass index (P = .002) and non-plantar wounds (P = .009) were the only patient- or wound-related factors associated with complete healing at 6 months. Spray-on skin resulted in high rates of complete healing at 6 months in patients with large diabetes-related foot wounds, but was not significantly better than standard care (Australian New Zealand Clinical Trials Registry: ACTRN12618000511235).

Temporal Trends in Incident Hospitalization for Diabetes-Related Foot Ulcer in Type 2 Diabetes: The Fremantle Diabetes Study.

OBJECTIVE: To determine whether, reflecting trends in other chronic complications, incident hospitalization for diabetes-related foot ulcer (DFU) has declined over recent decades in type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants with type 2 diabetes from the community-based Fremantle Diabetes Study phases I (FDS1; 1,296 participants, mean age 64.0 years, 48.6% males, recruited 1993-1996) and II (FDS2; 1,509 participants, mean age 65.4 years, 51.8% males, recruited 2008-2011) were followed from entry to first hospitalization for/with DFU, death, or 5 years (whichever came first). Incident rate ratios (IRRs) and incident rate differences (IRDs) were calculated for FDS2 versus FDS1 overall and in 10-year age-groups. Cox proportional hazards modeling determined independent predictors of first DFU hospitalization in the combined cohort. RESULTS: Incident DFU hospitalization (95% CI) was 1.9 (0.9-3.3)/1,000 person-years in FDS1 during 5,879 person-years of follow-up and 4.5 (3.0-6.4)/1,000 person-years in FDS2 during 6,915 person-years of follow-up. The crude IRR (95% CI) was 2.40 (1.17-5.28) (P = 0.013) and IRD 2.6 (0.7-4.5)/1,000 person-years (P = 0.010). The highest IR for any age-group was 23.6/1,000 person-years in FDS2 participants aged 31-40 years. Age at diabetes diagnosis (inverse), HbA1c, insulin use, height, ln(urinary albumin/creatinine), absence of any foot pulse, previous peripheral revascularization, and peripheral sensory neuropathy (PSN) were independent predictors of incident hospitalization for/with DFU. CONCLUSIONS: Incident DFU hospitalizations complicating type 2 diabetes increased between FDS phases, especially in younger participants, and were more likely in those with PSN, peripheral arterial disease, and suboptimal glycemic control at baseline.

Diabetes-related foot disease in Australia: a systematic review of the prevalence and incidence of risk factors, disease and amputation in Australian populations.

BACKGROUND: Diabetes-related foot disease (DFD) is a leading cause of global hospitalisation, amputation and disability burdens; yet, the epidemiology of the DFD burden is unclear in Australia. We aimed to systematically review the literature reporting the prevalence and incidence of risk factors for DFD (e.g. neuropathy, peripheral artery disease), of DFD (ulcers and infection), and of diabetes-related amputation (total, minor and major amputation) in Australian populations. METHODS: We systematically searched PubMed and EMBASE databases for peer-reviewed articles published until December 31, 2019. We used search strings combining key terms for prevalence or incidence, DFD or amputation, and Australia. Search results were independently screened for eligibility by two investigators. Publications that reported prevalence or incidence of outcomes of interest in geographically defined Australian populations were eligible for inclusion. Included studies were independently assessed for methodological quality and key data were extracted by two investigators. RESULTS: Twenty publications met eligibility and were included. There was high heterogeneity for populations investigated and methods used to identify outcomes. We found within diabetes populations, the prevalence of risk factors ranged from 10.0-58.8%, of DFD from 1.2-1.5%, and the incidence of diabetes-related amputation ranged from 5.2-7.2 per 1000 person-years. Additionally, the incidence of DFD-related hospitalisation ranged from 5.2-36.6 per 1000 person-years within diabetes populations. Furthermore, within inpatients with diabetes, we found the prevalence of risk factors ranged from 35.3-43.3%, DFD from 7.0-15.1% and amputation during hospitalisation from 1.4-5.8%. CONCLUSIONS: Our review suggests a similar risk factor prevalence, low but uncertain DFD prevalence, and high DFD-related hospitalisation and amputation incidence in Australia compared to international populations. These findings may suggest that a low proportion of people with risk factors develop DFD, however, it is also possible that there is an underestimation of DFD prevalence in Australia in the few limited studies, given the high incidence of hospitalisation and amputation because of DFD. Either way, studies of nationally representative populations using valid outcome measures are needed to verify these DFD-related findings and interpretations.

Spray on skin for diabetic foot ulcers: an open label randomised controlled trial.

BACKGROUND: One Australian loses a limb every 3 h as a result of infected diabetic foot ulcers (DFU). This common condition accounts for substantial morbidity and mortality for affected individuals and heavy economic costs for the health sector and the community. There is an urgent need to test interventions that improve wound healing time, prevent amputations and recurrent ulceration in patients presenting with DFU whilst improving quality of life and reducing health care costs. METHODS: One hundred and fifty eligible participants will be randomised to receive an autologous skin cell suspension, also termed 'spray-on' skin (ReCell®) or standard care interventions for their DFU. The primary outcome is complete wound healing at 6 months, but participants will be followed up for a total of 12 months to enable secondary outcomes including total overall costs, ulcer free days at 12 months and quality of life to be assessed. DISCUSSION: Outpatient costs for dressings, home nursing visits and outpatient appointments are key cost drivers for DFU. If spray-on skin is effective, large cost savings to WA Health will be realised immediately through a shortened time to healing, and through a higher proportion of patients achieving complete healing. Shortened healing times may enable participants to return to work earlier. Any economic benefits are likely to be amplified across Australia and other similar demographic settings where aging populations with increased diabetes rates are considered major future challenges. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000511235. Registered on 9 April 2018.

Epidemiology of diabetic foot disease and diabetes-related lower-extremity amputation in Australia: a systematic review protocol.

BACKGROUND: Diabetic foot disease is associated with major morbidity, mortality, costs, and reduction of a person's quality of life. Investigating the epidemiology of diabetic foot disease is the backbone of diabetic foot research and clinical practice, yet the full burden of diabetic foot disease in Australia is unknown. This study aims to describe the protocol for a systematic review of the epidemiology of diabetic foot disease and diabetes-related lower-extremity amputation in Australia. METHODS-SEARCH: The systematic review will be performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed and EMBASE will be searched for publications in any language and without restrictions to date. Two independent investigators will screen publications for eligibility, with publications reporting Australian population-based incidence or prevalence of diabetic foot disease or diabetes-related lower-extremity amputation to be included. Additionally, a forward literature search will be performed in Google Scholar, and a grey literature search will be performed to identify government publications. METHODS-ASSESSMENT: Quality assessment will be performed using customised checklists. The summary statistic used for each study will be an incidence or prevalence proportion of diabetic foot disease or diabetes-related lower-extremity amputation. The standard error for each proportion will be calculated. A meta-analysis will be performed when three or more publications of adequate quality, reporting on similar outcomes and in similar populations, are identified. DISCUSSION: The results of this systematic review can be used to adequately inform stakeholders in the field of diabetic foot disease on the extent of the problem in incidence and prevalence of diabetic foot disease in Australia, and to help guide appropriate use of resources to reduce the burden of this disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016050740.

Temporal changes in the prevalence and associates of diabetes-related lower extremity amputations in patients with type 2 diabetes: the Fremantle Diabetes Study.

BACKGROUND: To determine temporal changes in the prevalence and associates of lower extremity amputation (LEA) complicating type 2 diabetes. METHODS: Baseline data from the longitudinal observational Fremantle Diabetes Study (FDS) relating to LEA and its risk factors collected from 1296 patients recruited to FDS Phase 1 (FDS1) from 1993 to 1996 and from 1509 patients recruited to FDS Phase 2 (FDS2) from 2008 to 2011 were analysed. Multiple logistic regression was used to determine associates of prevalent LEA in individual and pooled phases. Generalised linear modelling was used to examine whether diabetes related LEA prevalence and its associates had changed between Phases. RESULTS: There were 15 diabetes-related LEAs at baseline in FDS1 (1.2 %) and 15 in FDS2 (1.0 %; P = 0.22 after age, sex and race/ethnicity adjustment). In multivariable analysis, independent associates of a baseline LEA in FDS1 were a history of vascular bypass surgery or revascularisation, urinary albumin:creatinine ratio, peripheral sensory neuropathy and cerebrovascular disease (P ≤ 0.035). In FDS2, prevalent LEA was independently associated with a history of vascular bypass surgery or revascularisation, past hospitalisation for/current foot ulcer and fasting serum glucose (P ≤ 0.001). In pooled analyses, a history of vascular bypass or revascularisation, past hospitalisation for/current foot ulcer at baseline, urinary albumin:creatinine ratio (P < 0.001), as well as FDS Phase as a binary variable [odds ratio (95 % confidence interval): 0.28 (0.09-0.84) for FDS2 vs FDS1, P = 0.023] were associated with a lower risk of LEA at study entry. CONCLUSIONS: The risk of prevalent LEA in two cohorts of patients with type 2 diabetes from the same Australian community fell by 72 % over a 15-year period after adjustment for important between-group differences in diabetes-related and other variables. This improvement reflects primary care foot health-related initiatives introduced between Phases, and should have important individual and societal benefits against a background of a progressively increasing diabetes burden.

Temporal changes in the prevalence and associates of foot ulceration in type 2 diabetes: the Fremantle Diabetes Study.

AIMS: To assess temporal changes in foot ulceration and its risk factors in community-based people with type 2 diabetes. METHODS: Baseline data from the longitudinal observational Fremantle Diabetes Study collected from 1993 to 1996 (Phase I) and 2008 to 2011 (Phase II) were analyzed. Generalized linear modeling was used to examine changes in foot ulcer prevalence and its associates between phases. Multiple logistic regression was used to determine associates of prevalent foot ulceration in individual and pooled phases. RESULTS: There were 16 foot ulcers among 1296 patients in Phase I (1.2%) and 23 in 1509 Phase II patients (1.5%; P=0.86 after age, sex and race/ethnicity adjustment). Glycemic and non-glycemic cardiovascular risk factors were better in Phase II, but diabetes duration was longer, peripheral sensory neuropathy (PSN) was more prevalent and more patients were Aboriginal (P<0.001) than in Phase I. In multivariable analysis of both phases and pooled data, diabetes duration and peripheral sensory neuropathy (PSN) were independent associates of foot ulceration (P≤0.026). Prior hospitalization for ulcer, intermittent claudication, any absent pedal pulse and Aboriginality were also significant in the pooled model (P≤0.009). CONCLUSIONS: Strong associations between foot ulcer and diabetes duration, PSN, symptomatic and clinically-detectable peripheral vascular disease were observed. Aboriginality also proved an independent risk factor. Since all these risk factors apart from intermittent claudication and impalpable foot pulses were more prevalent in Phase II, improved community- and hospital-based foot care between phases are likely to have attenuated the risk of foot ulcers in Phase II patients.

A comparison of two methods of foot health education: the Fremantle Diabetes Study Phase II.

AIMS: To compare the effectiveness of two different methods of education on foot health, behaviours and attitudes in patients with type 2 diabetes. METHODS: Community-based patients were consecutively allocated to written education (Group A) or an interactive educator-led session (Group B). A quantitative Foot Score (maximum 90 points score based on severity of treatable pathology), the Nottingham Assessment of Functional Foot Care (NAFFC) survey score (maximum 30 points reflecting frequency of foot care behaviours) and a 6-question survey of attitudes to foot complications were administered at baseline and 3 months. RESULTS: 154 patients (mean±SD age 68±10 years, 59.7% males, median [interquartile range] diabetes duration 11.5 [5.6-18.9] years) were recruited. There was a greater change (Δ) in Foot Score from baseline to 3 months in Group A (8.3±3.6, Δ-1.8 (95% CI: -2.4 to -1.2) vs Group B (6.8±2.6, Δ-0.1 (-0.7 to 0.4); P<0.001), but no change in NAFFC survey score in either group (P=0.13). In the attitudes survey, Group B felt they better understood how to prevent foot complications than Group A after education (P=0.031). CONCLUSIONS: Written information was more effective at improving foot health while interactive education improved confidence in undertaking preventive measures, suggesting that the most effective foot care education should include both components.

A longitudinal study of foot ulceration and its risk factors in community-based patients with type 2 diabetes: the Fremantle Diabetes Study.

AIMS: To determine the prevalence and associates of foot ulcer, and the subsequent incidence and predictors of first-ever hospitalisation for this complication, in well-characterised community-based patients with type 2 diabetes. METHODS: Baseline foot ulceration was ascertained in 1296 patients (mean age 64 years, 48.6% male, median diabetes duration 4.0 years) recruited to the longitudinal Fremantle Diabetes Study between 1993 and 1996. Incident hospitalisation for foot ulceration was monitored through validated data linkage until end-December 2010. RESULTS: At baseline, 16 participants (1.2%) had a foot ulcer which was independently associated with intermittent claudication, peripheral sensory neuropathy (PSN) and diabetes duration (P≤0.01). The incidence of hospitalisation for this complication in those without prior/prevalent foot ulceration was 5.21 per 1000 patient-years. This rate and other published data suggest that 1 in 7-10 foot ulcers require hospitalisation. In a Cox proportional hazards model, intermittent claudication and PSN were significant independent predictors of time to admission with foot ulceration, in addition to retinopathy, cerebrovascular disease, HbA1c, alcohol consumption, renal impairment, peripheral arterial disease and pulse pressure (P≤0.038). CONCLUSIONS: These data confirm PSN as an important risk factor for foot ulceration but, in contrast to some other studies, peripheral arterial disease was also a major independent contributor. Associations between hospitalisation for foot ulcer and both retinopathy and raised pulse pressure suggest a role for local microvascular dysfunction, while alcohol may have non-neuropathic toxic effects on skin/subcutaneous structures. The multifactorial nature of foot ulceration complicating type 2 diabetes may have implications for its management.