Lower Extremity Amputation In People Research Articles

Prevalence and incidence of peripheral neuropathy, peripheral artery disease, foot disease, and lower extremity amputation in people with diabetes in Ireland; a systematic review protocol.

Introduction Internationally, the prevalence of diabetes is increasing, and with this comes an increase in diabetes related complications. Diabetic foot disease is the most common lower extremity complication in people with diabetes, and is associated with major morbidity, mortality, and costs to health services. Despite this burden, the incidence and prevalence of diabetic foot disease is unknown in Ireland. This paper presents a protocol for a systematic review to examine the incidence and prevalence of diabetic foot disease in the Irish population. Methods A systematic review will be performed using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Pubmed, EMBASE, and Lenus, the Irish Health Research repository, will be searched for publications in any language and without restrictions to date. Title, abstract, and full text screening will be carried out independently by two investigators. Publications reporting on the incidence or prevalence of peripheral neuropathy, peripheral artery disease, ulceration, or amputation in people with diabetes in Ireland, from a defined geographical catchment area of Ireland, will be included. Joanna Briggs Institute (JBI) Critical Appraisal tool will be used to assess included studies methodological quality. Results will be reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Conclusion The results of this systematic review can be used to inform appropriate stakeholders on the incidence and prevalence of diabetic foot disease in Irish populations, enabling decision making around appropriate use of resources to help prevent, and improve management of this disease. Systematic review registration CRD42023472904

Mental health matters in community-based diabetic foot care

British Journal of Community NursingVol. 28, No. Sup3 EditorialMental health matters in community-based diabetic foot careSumarno Adi SubrataSumarno Adi SubrataE-mail Address: [email protected]Researcher at Wound Study Center (WOSCE) and Nursing Lecturer, Universitas Muhammadiyah Magelang, IndonesiaSearch for more papers by this authorSumarno Adi SubrataPublished Online:21 Feb 2023https://doi.org/10.12968/bjcn.2023.28.Sup3.S5AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Balikji J, Kiani P, Hendriksen PA, Hoogbergen MM, Garssen J, Verster JC. Impaired wound healing is associated with poorer mood and reduced perceived immune fitness during the COVID-19 pandemic: a retrospective survey. Health Sci Rep. 2022;5(5):e764. https://doi.org/10.1002/hsr2.764 Crossref, Medline, Google ScholarBrognara L, Volta I, Cassano VM, Navarro-Flores E, Cauli O. The association between cognitive impairment and diabetic foot care: role of neuropathy and glycated hemoglobin. Pathophysiology. 2020; 27(1):14-27. https://doi.org/10.3390/pathophysiology27010003 Crossref, Medline, Google ScholarFerrier L, Ski CF, O’Brien C et al.. Bridging the gap between diabetes care and mental health: perspectives of the Mental health IN DiabeteS Optimal Health Program (MINDS OHP). BMC Endocr Disord. 2021; 21, 96. https://doi.org/10.1186/s12902-021-00760-3 Crossref, Medline, Google ScholarFino P, Di Taranto G, Pierro A et al.. Depression risk among patients with chronic wounds. Eur Rev Med Pharmacol Sci. 2019;23(10):4310-4312. https://doi.org/10.26355/eurrev_201905_17936 Medline, Google ScholarJiang FH, Liu XM, Yu HR, Qian Y, Chen HL. The incidence of depression in patients with diabetic foot ulcers: a systematic review and meta-analysis. Int J Low Extrem Wounds. 2022;21(2):161-173. https://doi.org/10.1177/1534734620929892 Crossref, Medline, Google ScholarKamal S, Munahar S, Abbas A, Ito Y, Wahyudi A. Hospital bed for diabetes care: an invention to support professional and hygienic nursing practice. Mechanical Engineering for Society and Industry. 2021;1(1):7–13. https://doi.org/10.31603/mesi.5262 Crossref, Google ScholarKerr M. Diabetic foot care in England: an economic study. London: NICE; 2017. https://is.gd/ilgCoV (accessed 19 January 2023) Google ScholarKumar N, Huda F, Mani R, et al.. Role of hospital anxiety and depression on the healing of chronic leg ulcer: a prospective study. Int Wound J. 2020;17(6):1941-1947. https://doi.org/10.1111/iwj.13485 Crossref, Medline, Google ScholarNash M. Mental health nurses’ diabetes care skills - a training needs analysis. Br J Nurs. 2009;18(10):626, 628-30. https://doi.org/10.12968/bjon.2009.18.10.42472 Link, Google ScholarO’Neill SM, Kabir Z, McNamara G, Buckley CM. Comorbid depression and risk of lower extremity amputation in people with diabetes: systematic review and meta-analysis. BMJ Open Diabetes Research and Care. 2017;5(1):e000366. https://doi.org/10.1136/bmjdrc-2016-000366 Medline, Google ScholarPolikandrioti M, Vasilopoulos G, Koutelekos I et al.. Depression in diabetic foot ulcer: associated factors and the impact of perceived social support and anxiety on depression. Int Wound J. 2020;17(4):900-909. https://doi.org/10.1111/iwj.13348 Crossref, Medline, Google ScholarRazjouyan J, Grewal GS, Talal TK, Armstrong DG, Mills JL, Najafi B. Does physiological stress slow down wound healing in patients with diabetes? J Diabetes Sci Technol. 2017;11(4):685-692. https://doi.org/10.1177/1932296817705397 Crossref, Medline, Google ScholarSeaton PCJ, Cant RP, Trip HT. Quality indicators for a community-based wound care centre: an integrative review. Int Wound J. 2020;17(3):587-600. https://doi.org/10.1111/iwj.13308 Crossref, Medline, Google ScholarSubrata SA, Margono. Holistic care of patients with diabetic foot ulcers during the COVID-19 era: integration of Henderson’s need theory. Br J Nurs. 2022;31(15):S38-S49. https://doi.org/10.12968/bjon.2022.31.15.S38 Link, Google ScholarSubrata SA, Phuphaibul R. A nursing metaparadigm perspective of diabetic foot ulcer care. Br J Nurs. 2019a;28(6):S38-S50. https://doi.org/10.12968/bjon.2019.28.6.S38 Link, Google ScholarSubrata SA, Phuphaibul R. Diabetic foot ulcer care: a concept analysis of the term integrated into nursing practice. Scand J Caring Sci. 2019b;33(2):298-310. https://doi.org/10.1111/scs.12645 Crossref, Medline, Google ScholarWounds UK. Best practice recommendations for the implementation of a DFU treatment pathway. 2018. https://www.woundsinternational.com/resources/details/community-based-diabetic-foot-teams-are-they-the-way-forward (accessed 19 January 2023) Google Scholar FiguresReferencesRelatedDetails 2 March 2023Volume 28Issue Sup3ISSN (print): 1462-4753ISSN (online): 2052-2215 Metrics History Published online 21 February 2023 Published in print 2 March 2023 Information© MA Healthcare LimitedPDF download

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

To determine whether incident minor and major lower extremity amputations (LEAs) have declined in recent decades in type 2 diabetes. 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. 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. 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.

Temporal trends in major, minor and recurrent lower extremity amputations in people with and without diabetes in Belgium from 2009 to 2018

AimsThis study assessed temporal trends in the incidence of lower extremity amputations (LEA) in Belgium from 2009 to 2018, and subsequent secondary amputation rates. MethodsNationwide data on LEA were collected. Sex- and age-adjusted annual incidence rates were calculated. Time trends were analysed in negative binomial models. The incidence of secondary interventions, defined as either any ipsilateral reamputation or any contralateral amputation, was studied with death as competing risk. Results41 304 amputations were performed (13 247 major, 28 057 minor). In individuals with diabetes, the amputation rate (first amputation per patient per year) decreased from 143.6/100.000 person-years to 109.7 (IRR 0.97 per year, 95 %CI 0.96–0.98, p < 0.001). The incidence of major LEAs decreased from 56.2 to 30.7 (IRR 0.93, 95 %CI 0.91–0.94, p < 0.001); the incidence of minor amputations showed a non-significant declining trend in women (54.3 to 45.0/100 000 person years, IRR 0.97 per year, 95 %CI 0.96–0.99), while this remained stable in men with diabetes (149.2 to 135.3/100 000 person years, IRR 1.00 per year, 95 %CI 0.98–1.01). In individuals without diabetes, the incidence of major amputation didn’t change significantly, whereas minor amputation incidence increased (8.0 to 10.6, IRR 1.04, 95 %CI 1.03–1.05, p < 0.001). In individuals with diabetes, one-year secondary intervention rates were high (31.3% after minor, 18.4% after major LEA); the incidence of secondary amputations didn’t change. ConclusionsA significant decline in the incidence rate of major LEA was observed in people with diabetes. This decline was not accompanied by a significant rise in minor LEA. The incidence of secondary interventions remained stable.

IDF21-0505 Predictors of major lower extremity amputations in people with type 2 diabetes and foot ulcers

Background: Major lower extremity amputations (LEA) are a devastating complication in people with type 2 diabetes (T2D) who develop diabetic foot ulcers (DFU). In prospective research studies in primary care, DFUs can be difficult to evaluate as they are a low incident complication and a clinical outcome requires a long follow-up period.

National Rates of Lower Extremity Amputation in People With and Without Diabetes in a Multi-Ethnic Asian Population: a Ten Year Study in Singapore

Population level data from Asia on amputation rates in people with and without diabetes are extremely limited. Hence it is unclear how the rising diabetes prevalence in Asia has affected the amputation burden. The present study examined national amputation rates in people with and without diabetes in Singapore from 2008 to 2017 in the context of increasing diabetes prevalence and health system changes. This was a retrospective observational study using national population data for ages 16 - 100 years obtained from the Ministry of Health Singapore administrative datasets. Age sex standardised major and toe/ray amputation rates per 100 000 people with diabetes and per 100 000 people without diabetes were calculated. Rates were calculated overall and in each ethnic group (Chinese, Malay, Indian, Others), with trends over time calculated using joinpoint trend analysis. In addition, age specific rates, relative risk (RR) of amputation in diabetics compared with non-diabetics and proportion of amputations in the population attributable to diabetes were also calculated. Between 2008 and 2017, the database included 3.6 million unique individuals, of whom 75% were Chinese, 8.6% Malay, 7.9% Indian, and 8.4% Others. Of those, 413 486 (11%) had diabetes. Major amputation rates in people with diabetes remained stable (2008: 99.5/100 000; 2017: 95.0/100 000 people with diabetes, p= .91) as did toe/ray amputation rates. Rates in people without diabetes were substantially lower, with major amputation rates decreasing significantly (2008: 3.0/100 000; 2017: 2.1/100 000 people without diabetes, 3% annual reduction, p= .048). Diabetes related amputation rates were highest in Malays and lowest in Chinese. Diabetes related major amputation rates declined significantly among Chinese (3.1% annual reduction, p < .038). While the RR for amputations in diabetes remained stable, the proportion of major amputations attributable to diabetes increased from 63.6% in 2008 to 81.7% in 2017 (3% annual increase, p= .003). Diabetes related major and toe/ray amputation rates have remained stable but relatively high in Singapore compared with other countries, and the proportion of amputations attributable to diabetes has increased over time. More research is needed to understand the aetiopathological, sociocultural, and health system factors that may underlie the continued high rates of diabetes related amputations in this population.

TP5.2.9 Mortality following major lower extremity amputation in people with and without diabetes in Scotland 2004-2013

Abstract Aim To describe short and longer-term mortality following major lower extremity amputation (LEA) by diabetes status over two time periods. Methods A retrospective cohort study of patients who underwent major LEA between 2004 and 2013 was conducted based on linkage of national population-based hospital records and a register of people with diagnosed diabetes. Post-operative mortality was estimated at 30 days, one year and where available, five years. Using logistic regression models, we estimated the odds of death associated with diabetes adjusted for age, sex and socio-economic status within these time points compared to the non-diabetic population stratified by type of diabetes and five-year calendar periods. Results There were a total of 5436 people who received an amputation during the study period of whom approximately 40% had diabetes. Overall mortality for the 2004-8 and 2009-13 cohorts respectively was not significantly different at 7.9% and 7.3% at 30 days and 31% and 27% at one year. Almost 64% of the 2004-8 cohort were dead within five years. The only statistically significantly associations between diabetes and mortality were observed within five year follow-up of the 2004-8 cohort with odds ratios (95% CI) compared to the non-diabetic population of 1.62 (1.17, 2.26) for type 1 diabetes and 1.38 (1.14, 1.66) for type 2 diabetes. Conclusions An adverse association between diabetes and mortality after LEA only became apparent in longer term follow-up.

Factors influencing lower extremity amputation outcomes in people with active foot ulceration in regional Australia: A retrospective cohort study.

Australia has the second highest rate of non-traumatic lower extremity amputation (LEA) globally. Australia's large geographical size is one of the biggest challenges facing limb preservation services and may be contributing to LEA. The aim of this study was to determine what factors contribute to the likelihood of LEA in people with active foot ulceration in regional Australia. This retrospective cohort study audited patients with active foot ulceration in a multidisciplinary high risk foot service (HRFS) in regional Australia. Neurological, vascular and wound characteristics were systematically extracted, along with demographic information. Participants were followed for at least 12 months until healing or LEA occurred. Correlations between LEA and clinical and demographic characteristics were assessed using the Pearson's product moment correlation coefficient and chi squared test for independence. Significant variables (p < 0.05) were included in the model. Direct logistic regression assessed the independent contribution of significantly correlated variables on the likelihood of LEA. Of note, 1876 records were hand screened with 476 participants (25%) meeting the inclusion criteria. Geographical distance from the HRFS, toe systolic pressure (TSP), diabetes and infection were all significantly correlated with LEA and included in the logistic regression model. TSP decrease of 1 mmHg (OR 1.02, 95% CI 1.01-1.03), increased geographical distance (1km) from HRFS (OR 1.006, 95% CI 1.001-1.01) infection (OR 2.08, 95% CI 1.06-4.07) and presence of diabetes (OR 3.77, 95% CI 1.12-12.65) were all significantly associated with increased likelihood of LEA. HRFS should account for the disparity in outcomes between patients living in close proximity to their service, compared to those in rural areas. Optimal management of diabetes, vascular perfusion and control of infection may also contribute to preventing LEA in people with active foot ulceration.

1705 Mortality Following Major Lower Extremity Amputation in People with And Without Diabetes in Scotland 2004-2013

Abstract Aim To describe short and longer-term mortality following major lower extremity amputation (LEA) by diabetes status over two time periods Method A retrospective cohort study of patients who underwent major LEA between 2004 and 2013 was conducted based on linkage of national population-based hospital records and a register of people with diagnosed diabetes. Post-operative mortality was estimated at 30 days, one year and where available, five years. Using logistic regression models, we estimated the odds of death associated with diabetes adjusted for age, sex and socio-economic status within these time points compared to the non-diabetic population stratified by type of diabetes and five-year calendar periods. Results There were a total of 5436 people who received an amputation during the study period of whom approximately 40% had diabetes. Overall mortality for the 2004-8 and 2009-13 cohorts respectively was not significantly different at 7.9% and 7.3% at 30 days and 31% and 27% at one year. Almost 64% of the 2004-8 cohort were dead within five years. The only statistically significantly associations between diabetes and mortality were observed within five-year follow-up of the 2004-8 cohort with odds ratios (95% CI) compared to the non-diabetic population of 1.62 (1.17, 2.26) for type 1 diabetes and 1.38 (1.14, 1.66) for type 2 diabetes. Conclusions An adverse association between diabetes and mortality after LEA only became apparent in longer term follow-up.

Risk factors and incidence over time for lower extremity amputations in people with type 1 diabetes: an observational cohort study of 46,088 patients from the Swedish National Diabetes Registry

Aims/hypothesisThe aim of this work was to study the incidence over time of lower extremity amputations and determine variables associated with increased risk of amputations in people with type 1 diabetes.MethodsIndividuals with type 1 diabetes registered in the Swedish National Diabetes Registry with no previous amputation from 1 January 1998 and followed to 2 October 2019 were included. Time-updated Cox regression and gradient of risk per SD were used to evaluate the impact of risk factors on the incidence of amputation. Age- and sex-adjusted incidences were estimated over time.ResultsOf 46,088 people with type 1 diabetes with no previous amputation (mean age 32.5 years [SD 14.5], 25,354 [55%] male sex), 1519 (3.3%) underwent amputation. Median follow-up was 12.4 years. The standardised incidence for any amputation in 1998–2001 was 2.84 (95% CI 2.32, 3.36) per 1000 person-years and decreased to 1.64 (95% CI 1.38, 1.90) per 1000 person-years in 2017–2019. The incidence for minor and major amputations showed a similar pattern. Hyperglycaemia and renal dysfunction were the strongest risk factors for amputation, followed by older age, male sex, cardiovascular comorbidities, smoking and hypertension. Glycaemic control and age- and sex-adjusted renal function improved during the corresponding time period as amputations decreased.Conclusions/interpretationThe incidence of amputation and of the most prominent risk factors for amputation, including renal dysfunction and hyperglycaemia, has improved considerably during recent years for people with type 1 diabetes. This finding has important implications for quality of life, health economics and prognosis regarding CVD, indicating a trend shift in the treatment of type 1 diabetes.Graphical abstract

52-OR: Risk Factors and Incidence over Time for Lower Extremity Amputations in Persons with Type 1 Diabetes: An Observational Cohort Study of 46,008 Patients from the Swedish National Diabetes Registry

Background: Lower extremity amputations in people with diabetes is a major source of disability and distress and it constitutes a significant financial burden for the healthcare system. Risk factors and current risks for amputation in persons with type 1 diabetes have not been extensively studied. Methods: Persons with type 1 diabetes registered in the Swedish National Diabetes Registry with no previous amputation from 1998 and followed until 2019 were included. Time-updated Cox regression and gradient of risk per SD were used to evaluate the impact of risk factors on the incidence of amputation. Age and sex adjusted incidences were estimated over time. Findings: Of 46,008 persons with type 1 diabetes with no previous amputation and a mean age of 32.5 years (SD 14.5) and 25 354 (55%) male, 1,519 (3.3%) underwent amputation. Median follow-up was 12.4 years. The age and sex adjusted incidence for any amputation decreased over time. The standardized incidence was 1998-2001 2.84 (95% CI 2.32-3.36) per 1000 patient years and decreased to 1.64 (95% CI 1.38-1.90) in 2017-2019 along with improved glycaemic control (0.02% [95% CI 0.02-0.02] per year) and renal function (0.23 ml/min/1.73m² [95% CI 0.21-0.24] per year). Risk factors for amputations were hyperglycemia, renal dysfunction, older age, male gender, cardiovascular comorbidities, smoking and hypertension. Interpretation: Prognosis has improved considerably regarding the risk of amputations in persons with type 1 diabetes while glycaemic control and renal function improved which were the most prominent risk factors. Disclosure S. Hallström: None. A. Svensson: None. A. Pivodic: None. A. F. Olafsdottir: None. M. Londahl: Advisory Panel; Self; Abbott, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Sanofi. H. Wedel: None. M. Lind: Consultant; Self; AstraZeneca, Eli Lilly and Company, Other Relationship; Self; Novo Nordisk, Research Support; Self; Dexcom, Inc. Funding Novo Nordisk Foundation; Swedish State

Health service organisation impact on lower extremity amputations in people with type 2 diabetes with foot ulcers: systematic review and meta-analysis

AimsDespite the evidence available on the epidemiology of diabetic foot ulcers and associated complications, it is not clear how specific organizational aspects of health care systems can positively affect their clinical trajectory. We aim to evaluate the impact of organizational aspects of care on lower extremity amputation rates among people with type 2 diabetes affected by foot ulcers.MethodsWe conducted a systematic review of the scientific literature published between 1999 and 2019, using the following key terms as search criteria: people with type 2 diabetes, diagnosed with diabetic foot ulcer, treated with specific processes and care pathways, and LEA as primary outcome. Overall results were reported as pooled odds ratios and 95% confidence intervals obtained using fixed and random effects models.ResultsA total of 57 studies were found eligible, highlighting the following arrangements: dedicated teams, care pathways and protocols, multidisciplinary teams, and combined interventions. Among them, seven studies qualified for a meta-analysis. According to the random effects model, interventions including any of the four arrangements were associated with a 29% reduced risk of any type of lower extremity amputation (OR = 0.71; 95% CI 0.52–0.96). The effect was larger when focusing on major LEAs alone, leading to a 48% risk reduction (OR = 0.52; 95% CI 0.30–0.91).ConclusionsSpecific organizational arrangements including multidisciplinary teams and care pathways can prevent half of the amputations in people with diabetes and foot ulcers. Further studies using standardized criteria are needed to investigate the cost-effectiveness to facilitate wider implementation of improved organizational arrangements. Similarly, research should identify specific roadblocks to translating evidence into action. These may be structures and processes at the health system level, e.g. availability of professionals with the right skillset, reimbursement mechanisms, and clear organizational intervention implementation guidelines.

Secular trends in rates of hospitalisation for lower extremity amputation and 1year mortality in people with diabetes in Hong Kong, 2001-2016: a retrospective cohort study.

We aimed to describe trends in rates of hospitalisation for lower extremity amputation (LEA) and 1year mortality rates after LEA in people with diabetes in Hong Kong between 2001 and 2016. The Hong Kong Diabetes Surveillance Database is a territory-wide population-based diabetes cohort (N = 770,078) identified from the Hong Kong Hospital Authority electronic medical system. We identified LEA events using ICD-9 procedure codes and 1year mortality after LEA from linkage to the Hong Kong Death Registry. Joinpoint regression models were used to describe the trends. Between 2001 and 2016, 6113 hospitalisations for LEAs in men and 4149 in women were recorded in the Hong Kong Diabetes Surveillance Database. The rates of minor LEAs declined by 48.6% (average annual per cent change [AAPC]: -3.8; 95% CI -5.7, -1.9) in men and by 59.5% (AAPC: -6.3; 95% CI -10.6, -1.8) in women. The rates of major LEAs declined by 77.9% (AAPC: -8.0; 95% CI -9.6, -6.5) in men and by 79.3% (AAPC: -10.4; 95% CI -13.1, -7.6) in women. The cumulative 1year mortality rates after minor and major LEAs were 18.5% and 41.8% in men, and 21.3% and 42.0% in women, respectively, for the whole period. No change was detected in 1year mortality rates during the surveillance in both sexes. Although hospitalisation rates for LEAs have declined overall in people with diabetes, there were no improvements in 1year mortality rates after LEA. Continuous efforts are needed to further prevent LEAs and improve the survival rate of people undergoing LEAs. Graphical abstract.

1497-P: Secular Trends in Incidence and One-Year Mortality Rates of Lower Extremity Amputation in People with Diabetes in Hong Kong between 2001 and 2016

Objective: Diabetes is a leading cause of nontraumatic lower extremity amputation (LEA). We describe the secular trends in incidence rates of LEA and one-year mortality rates after LEA in people with diabetes in Hong Kong between 2001 and 2016. Methods: The Hong Kong Diabetes Surveillance Database (HKDSD) is a territory-wide population-based diabetes cohort identified from the Hong Kong Hospital Authority electronic medical system. We identified LEA events using ICD-9 procedure codes and that of one-year mortality after LEAs from the linkage to the Hong Kong Death Registry. We used Joinpoint regression models to describe the trends in incidence of LEAs from 2001 to 2016 and one-year mortality rates after LEAs from 2001 to 2015. Results: Between 2001 and 2016, a total of 390,071 men and 380,007 women with diabetes aged 20 years or older were included in the HKDSD, among whom 6,113 LEAs in men and 4,149 LEAs in women were recorded. The event rates of minor LEAs declined by 48.6% (average annual percent change [AAPC]: -3.8, 95% CI -5.7, -1.9) from 14.0 to 7.2 per 10,000 in men and by 59.5% (AAPC: -6.3, 95% CI -10.6, -1.8) from 7.9 to 3.2 per 10,000 in women. The rates of major LEAs declined by 77.9% (AAPC: -8.0, 95% CI -9.6, -6.5) from 19.5 to 4.3 per 10,000 in men and by 79.3% (AAPC: -10.4, 95% CI -13.1, -7.6) from 11.6 to 2.4 per 10,000 in women. The one-year mortality rates after both minor and major LEAs remained constant during the surveillance period in both sexes. The AAPC for one-year mortality rates was 1.5 (95% CI -3.0, 6.1) in men and 0.6 (95% CI -4.7, 6.1) in women after minor LEAs, and was -2.1 (95% CI -4.8, 0.6) in men and 2.6 (-1.4, 6.7) in women after major LEAs. Conclusions: Although the event rates of LEAs have declined overall in people with diabetes in Hong Kong, there was no improvement in one-year mortality rates after LEAs. Urgent action to improve the quality of care and ongoing surveillance after LEAs in people with diabetes is needed. Disclosure H. Wu: None. A. Yang: None. E.S. Lau: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. A.P. Kong: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Sanofi. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. E. Chow: None. W. So: None. J.C. Chan: None. A. Luk: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Roche Pharma. Other Relationship; Self; Merck Sharp &amp; Dohme Corp.

220-OR: Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Risk for Lower Extremity Amputation in People with Type 2 Diabetes

Patients with diabetes have an increased risk for lower limb amputation (LLA) but biomarker to assess risk of LLA is lacking. Adrenomedullin (ADM), a vasodilator peptide, has been shown to be associated with cardiovascular and renal risk in diabetes. The aim of this study is to assess the association between plasma MR-proADM (a surrogate of ADM), allelic variation in the ADM gene and the risk for LLA in cohorts of patients with type 2 diabetes. We studied 4532 participants of the DIABHYCAR and SURDIAGENE cohorts (men 70%, mean age 66, mean duration of diabetes 13 years, A1c 8,0%). MR-proADM was measured by immunofluorescence. Five SNPs were chosen in the haplotype block containing the ADM gene (chr11p15.4): rs4399321, rs11042725, rs7944706, rs2957692 and rs2957717. The mean follow-up was 5.3 years. Incidence of LLA by tertiles of MR-proADM (T1, T2, T3) was 1.0% (T1), 1.9% (T2) et 4.7% (T3) (p&amp;lt;0,001). In a Cox multivariable analysis model (adjusted for cohort, age, sex, diabetes duration, hypertension, A1c, cholesterol, history of peripheral arterial disease and glomerular filtration rate eGFR), HR for LLA was 4.21 (2.18-8.66; p&amp;lt;0.001) for T3 vs. T1, 2.46 (1.50-4.12; p=0.003) for T3 vs. T2 and 1.82 (1.25-2.67; p=0.002) for 1 unit of log [ADM]. All SNPs were significantly associated with baseline plasma ADM. Four were significantly associated with LLA: HR adjusted for sex, age, duration of diabetes, A1c, eGFR and cohort: 1.40 (1.046 - 1.84; p=0.02) for the G-allele of rs4399321 in a codominant model; 1.71 (1.13 - 2.54; p=0.01) for the AA vs. CX genotype of rs11042725; 1.61 (1.09 - 2.35; p=0.02, for the GG vs. AX genotype of rs7944706; 1.37 (1.06 - 1.77; p=0.04) for the G-allele of rs2957692 in a codominant model. We observed an association of plasma ADM with LLA and of allelic variations in the AMP locus with plasma ADM and with LLA in a large population of people with type 2 diabetes. This pattern of mendelian randomisation supports the causality of the association of plasma ADM with LLA. Disclosure L. Potier: Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. R. Roussel: Advisory Panel; Self; Abbott, AstraZeneca, Diabnext, Eli Lilly and Company, Merck &amp; Co., Inc., Mundipharma International, Novo Nordisk A/S, Sanofi-Aventis. P. Saulnier: None. F. Fumeron: None. K. Mohammedi: None. G. Velho: None.

67-OR: Plasma Copeptin and Risk for Lower Extremity Amputation in People with Type 1 and Type 2 Diabetes

Recently, an increased risk of lower extremity amputation (LEA) was observed with canagliflozin, a SGLT2 inhibitor, in the CANVAS trial although observational studies showed conflicting results. This association could be related to the contraction of plasma volume induced by SGLT2 inhibition. In this case, copeptin, a surrogate marker of vasopressin, should be associated with LEA. Our aim was to analyze the association between LEA and plasma copeptin in 4 cohorts of patients with type 1 and type 2 diabetes (T1D, T2D). Analysis were done in 2 pooled cohorts of patients with type 2 diabetes (DIABHYCAR, SURDIAGENE, n=4532) and 2 pooled cohorts of patients with type 1 diabetes (GENESIS, GENEDIAB, n=712). Cox regression model was fitted to compute hazard ratio (HR) and 95% CI for incident LEA by tertiles of copeptin at baseline. C-statistic, integrated discrimination improvement (IDI) and continuous net reclassification improvement (cNRI) were used to assess the prognostic value of copeptin in LEA discrimination. Mean follow-up was 5.3 years for DT2 and 6.3 for DT1. Incidence of LEA was 1.6% (T1), 2.6% (T2) and 3.3% (T3) for DT2 (p&amp;lt;0.001) and 3.9% (T1), 3.3% (T2) and 10% (T3) for DT1 (p=0.003). In a Cox multivariable analysis model (adjusted for cohort, sex, diabetes duration, hypertension, previous cardiovascular and peripheral arterial disease and glomerular filtration rate), HR for LEA was 1.91 (1.13-3.24; p=0.016) in DT2 and 2.76 (1.05-7.66; p=0.04) in DT1, both for T3 vs. T1. Plasma copeptin yielded incremental information for the risk of LEA in DT2: C-statistic change 0.012 (p=0.005), IDI: 0.007 (0.005-0.025, p=0.05), cNRI: 0.13 (0.03-0.29, p=0.03). Plasma copeptin is significantly associated with an increased risk of LEA in patients with T1D and T2D. Mechanisms underlying this association are not known but could be related to hydration status. Our results suggest a potential role of contraction volume effect of SGLT2 inhibitor in the higher risk of LEA possibly associated with this class. Disclosure L. Potier: Advisory Panel; Self; Merck Sharp &amp; Dohme Corp. Consultant; Self; Sanofi. R. Roussel: Advisory Panel; Self; Merck Sharp &amp; Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. K. Mohammedi: None. P. Saulnier: None. M. Marre: Advisory Panel; Self; Servier. Board Member; Self; Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. S. Hadjadj: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi, Servier. Research Support; Self; Bayer AG, Janssen Research &amp; Development. Speaker's Bureau; Self; Abbott, Valbiotis. G. Velho: None.

Excess risk of lower extremity amputations in people with type 1 diabetes compared with the general population: amputations and type 1 diabetes

ObjectiveThis study investigates how the excess risk of lower extremity amputations (amputations) in people with type 1 diabetes mellitus (DM) differs from the general population by diabetes duration, glycemic control,...

Decreasing rates of major lower-extremity amputation in people with diabetes but not in those without: a nationwide study in Belgium

Aims/hypothesisThe reduction of major lower-extremity amputations (LEAs) is one of the main goals in diabetes care. Our aim was to estimate annual LEA rates in individuals with and without diabetes in Belgium, and corresponding time trends.MethodsData for 2009–2013 were provided by the Belgian national health insurance funds, covering more than 99% of the Belgian population (about 11 million people). We estimated the age–sex standardised annual amputation rate (first per year) in the populations with and without diabetes for major and minor LEAs, and the corresponding relative risks. To test for time trends, Poisson regression models were fitted.ResultsA total of 5438 individuals (52.1% with diabetes) underwent a major LEA, 2884 people with above- and 3070 with below-the-knee major amputations. A significant decline in the major amputation rate was observed in people with diabetes (2009: 42.3; 2013: 29.9 per 100,000 person-years, 8% annual reduction, p < 0.001), which was particularly evident for major amputations above the knee. The annual major amputation rate remained stable in individuals without diabetes (2009: 6.1 per 100,000 person-years; 2013: 6.0 per 100,000 person-years, p = 0.324) and thus the relative risk reduced from 6.9 to 5.0 (p < 0.001). A significant but weaker decrease was observed for minor amputation in individuals with and without diabetes (5% and 3% annual reduction, respectively, p < 0.001).Conclusions/interpretationIn this nationwide study, the risk of undergoing a major LEA in Belgium gradually declined for individuals with diabetes between 2009 and 2013. However, continued efforts should be made to further reduce the number of unnecessary amputations.

Lower-extremity amputations in people with and without diabetes in Germany, 2008-2012 - an analysis of more than 30 million inhabitants.

Background and purposeLower-extremity amputations (LEAs) in people with diabetes are associated with reduced quality of life and increased health care costs. Detailed knowledge on amputation rates (ARs) is of utmost importance for future health care and economics strategies. We conducted the present cohort study in order to estimate the incidences of LEA as well as relative and attributable risk due to diabetes and to investigate time trends for the period 2008–2012.MethodsOn the basis of the administrative data from three large branches of German statutory health insurers, covering ~34 million insured people nationwide (about 40% of the German population), we estimated age-sex-standardized AR (first amputation per year) in the populations with and without diabetes for any, major, and minor LEAs. Time trends were analyzed using Poisson regression.ResultsA total of 108,208 individuals (diabetes: 67.3%; mean age 72.6 years) had at least one amputation. Among people with diabetes, we observed a significant reduction in major and minor ARs during 2008–2012 from 81.2 (95% CI 77.5–84.9) to 58.4 (55.0–61.7), and from 206.1 (197.3–214.8) to 177.0 (169.7–184.4) per 100,000 person-years, respectively. Among people without diabetes, the major AR decreased significantly from 14.3 (13.9–14.8) to 11.6 ([11.2–12.0], 12.0), whereas the minor AR increased from 15.8 (15.3–16.3) to 17.0 (16.5–17.5) per 100,000 person-years. The relative risk (RR) comparing the diabetic with the nondiabetic populations decreased significantly for both major and minor LEAs (4% and 5% annual reduction, respectively).ConclusionIn this large nationwide population, we still found higher major and minor ARs among people with diabetes compared with those without diabetes. However, AR and RR of major and minor LEAs in the diabetic compared with the nondiabetic population decreased significantly during the study period, confirming a positive trend that has been observed in smaller and regional studies in recent years.

Comorbid depression and risk of lower extremity amputation in people with diabetes: systematic review and meta-analysis

ObjectiveTo compare the risk of lower extremity amputation (LEA) in people with diabetes with and without comorbid depression.Research design and methodsA systematic review of the published literature was conducted. Six...