{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:43:16Z","timestamp":1790602996444,"version":"4.1.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"associazione salute con stile"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lower extremity amputations (LEA) are associated with a high mortality and medical expenditure. Diabetes accounts for 45% to 70% of LEA and is one of the most potent risk factors for peripheral artery diseases (PAD). The existence of a link between the recent relaxation of glycemic targets and the resurgence of LEA is suggested from the analysis of adult participants in the National Health and Nutrition Examination Survey (NHANES) between 2010 and 2015, when diabetes-related LEA increased by more than 25% associated with a decline in glycemic control. Indeed, in \u201cthe perfect wave\u201d of NHANES, including the years 2007\u20132010, there was the highest number of diabetic people with hemoglobin A1c (HbA1c), non-high-density lipoprotein (HDL) cholesterol and blood pressure levels at their respective targets, associated with the lowest number of LEA. Until now, the ACCORD study, testing the role of aggressive vs conventional glucose control, and the LEADER trial, evaluating the effects of liraglutide versus placebo, have shown a reduced incidence of LEA in people with type 2 diabetes. The results of ongoing clinical trials involving glucagon-like peptide-1 receptor agonists (GLP-1RA, liraglutide or semaglutide) hopefully will tell us whether the wider use of these drugs may provide additional vascular benefits for diabetic people affected by PAD to decrease their risk of LEA.<\/jats:p>","DOI":"10.1186\/s12933-021-01325-3","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T15:04:14Z","timestamp":1625583854000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Up and down waves of glycemic control and lower-extremity amputation in diabetes"],"prefix":"10.1186","volume":"20","author":[{"given":"Paola","family":"Caruso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Scappaticcio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Ida","family":"Maiorino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9377-873X","authenticated-orcid":false,"given":"Dario","family":"Giugliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"1325_CR1","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1056\/NEJMsa2032271","volume":"384","author":"M Fang","year":"2021","unstructured":"Fang M, Wang D, Coresh J, Selvin E. Trends in diabetes treatment and control in U.S. adults, 1999\u20132018. N Engl J Med. 2021;384:2219\u201328.","journal-title":"N Engl J Med."},{"key":"1325_CR2","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1001\/jama.2019.3471","volume":"321","author":"EW Gregg","year":"2019","unstructured":"Gregg EW, Hora I, Benoit SR. Resurgence in diabetes-related complications. JAMA. 2019;321:1867\u20138.","journal-title":"JAMA"},{"key":"1325_CR3","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.1056\/NEJMoa1310799","volume":"370","author":"EW Gregg","year":"2014","unstructured":"Gregg EW, Li Y, Wang J, et al. Changes in diabetes-related complications in the United States, 1990\u20132010. N Engl J Med. 2014;370:1514\u201323.","journal-title":"N Engl J Med"},{"key":"1325_CR4","doi-asserted-by":"publisher","first-page":"50","DOI":"10.2337\/dc18-1380","volume":"42","author":"LS Geiss","year":"2019","unstructured":"Geiss LS, Li Y, Hora I, Albright A, Rolka D, Gregg EW. Resurgence of diabetes-related nontraumatic lower-extremity amputation in the young and middle-aged adult U.S. population. Diabetes Care. 2019;42:50\u20134.","journal-title":"Diabetes Care."},{"key":"1325_CR5","doi-asserted-by":"publisher","first-page":"e875","DOI":"10.1161\/CIR.0000000000000967","volume":"143","author":"MA Creager","year":"2021","unstructured":"Creager MA, Matsushita K, Arya S, et al. Reducing nontraumatic lower-extremity amputations by 20% by 2030: Time to get to our feet. A policy statement from the American Heart Association. Circulation. 2021;143:e875\u201391.","journal-title":"Circulation."},{"key":"1325_CR6","doi-asserted-by":"publisher","first-page":"S151","DOI":"10.2337\/dc21-S011","volume":"44","author":"American Diabetes Association","year":"2021","unstructured":"American Diabetes Association. 11: Microvascular complications and foot care: Standards of Medical Care in Diabetes\u20132021. Diabetes Care. 2021;44:S151\u201367.","journal-title":"Diabetes Care"},{"key":"1325_CR7","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1056\/NEJMoa0802987","volume":"358","author":"ADVANCE Collaborative Group","year":"2008","unstructured":"ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560\u201372.","journal-title":"N Engl J Med"},{"key":"1325_CR8","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1056\/NEJMoa0802743","volume":"358","author":"Action to Control Cardiovascular Risk in Diabetes Study Group","year":"2008","unstructured":"Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545\u201359.","journal-title":"N Engl J Med"},{"key":"1325_CR9","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1056\/NEJMoa0808431","volume":"360","author":"W Duckworth","year":"2009","unstructured":"Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129\u201339.","journal-title":"N Engl J Med"},{"key":"1325_CR10","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.1007\/s00125-009-1470-0","volume":"52","author":"FM Turnbull","year":"2009","unstructured":"Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52:2288\u201398.","journal-title":"Diabetologia"},{"key":"1325_CR11","doi-asserted-by":"publisher","first-page":"421","DOI":"10.7326\/0003-4819-141-6-200409210-00007","volume":"141","author":"E Selvin","year":"2004","unstructured":"Selvin E, Marinopoulos S, Berkenblit G, et al. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med. 2004;141:421\u201331.","journal-title":"Ann Intern Med"},{"key":"1325_CR12","doi-asserted-by":"publisher","first-page":"701","DOI":"10.2337\/dc15-2283","volume":"39","author":"The ACCORD Study Group","year":"2016","unstructured":"The ACCORD Study Group. Nine-year effects of 37 years of intensive glycemic control on cardiovascular outcomes. Diabetes Care. 2016;39:701\u20138.","journal-title":"Diabetes Care."},{"key":"1325_CR13","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.jamcollsurg.2018.09.021","volume":"227","author":"MP Goldman","year":"2018","unstructured":"Goldman MP, Clark CJ, Craven TE, et al. Effect of intensive glycemic control on risk of lower extremity amputation. J Am Coll Surg. 2018;227:596\u2013604.","journal-title":"J Am Coll Surg"},{"key":"1325_CR14","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12933-021-01229-2","volume":"20","author":"D Giugliano","year":"2021","unstructured":"Giugliano D, Maiorino MI, Bellastella G, Esposito K. The residual cardiorenal risk in type 2 diabetes. Cardiovasc Diabetol. 2021;20:36.","journal-title":"Cardiovasc Diabetol"},{"key":"1325_CR15","doi-asserted-by":"publisher","first-page":"2229","DOI":"10.2337\/dc18-1094","volume":"41","author":"K Dhatariya","year":"2018","unstructured":"Dhatariya K, Bain SC, Buse JB, et al. LEADER Publication Committee on behalf of the LEADER Trial Investigators. The impact of liraglutide on diabetes-related foot ulceration and associated complications in patients with type 2 diabetes at high risk for cardiovascular events: results from the LEADER trial. Diabetes Care. 2018;41:2229\u201335.","journal-title":"Diabetes Care."},{"key":"1325_CR16","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1001\/jamainternmed.2018.3034","volume":"178","author":"HY Chang","year":"2018","unstructured":"Chang HY, Singh S, Mansour O, Baksh S, Alexander GC. Association between sodium-glucose cotransporter 2 inhibitors and lower extremity amputation among patients with type 2 diabetes. JAMA Intern Med. 2018;178:1190\u20138.","journal-title":"JAMA Intern Med"},{"key":"1325_CR17","doi-asserted-by":"crossref","unstructured":"Correction to: Lin C, Zhu X, Cai X, et al. SGLT2 inhibitors and lower limb complications: an updated meta-analysis. Cardiovasc Diabetol. 2021;20:119.","DOI":"10.1186\/s12933-021-01306-6"},{"key":"1325_CR18","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1056\/NEJMra1615439","volume":"376","author":"DG Armstrong","year":"2017","unstructured":"Armstrong DG, Boulton AJM, Bus SA. Diabetic foot ulcers and their recurrence. N Engl J Med. 2017;376:2367\u201375.","journal-title":"N Engl J Med"},{"key":"1325_CR19","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/s12933-020-01159-5","volume":"19","author":"W Ling","year":"2020","unstructured":"Ling W, Huang Y, Huang Y-M, Fan R-R, Sui Y, Zhao H-L. Global trend of diabetes mortality attributed to vascular complications, 2000\u20132016. Cardiovasc Diabetol. 2020;19:182.","journal-title":"Cardiovasc Diabetol"},{"key":"1325_CR20","doi-asserted-by":"publisher","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","volume":"157","author":"P Saeedi","year":"2019","unstructured":"Saeedi P, Petersohn I, Salpea P et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes Res Clin Pract. 2019;157:107843.","journal-title":"Diabetes Res Clin Pract"}],"container-title":["Cardiovascular Diabetology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-021-01325-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12933-021-01325-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-021-01325-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T15:06:16Z","timestamp":1625583976000},"score":1,"resource":{"primary":{"URL":"https:\/\/cardiab.biomedcentral.com\/articles\/10.1186\/s12933-021-01325-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,6]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1325"],"URL":"https:\/\/doi.org\/10.1186\/s12933-021-01325-3","relation":{},"ISSN":["1475-2840"],"issn-type":[{"value":"1475-2840","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,6]]},"assertion":[{"value":"16 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"D.G. received honoraria for speaking at meetings from Novartis, Sanofi, Lilly, Astrazeneca, and NovoNordisk. M.I.M. received honoraria for speaking at meetings from AstraZeneca, Boehringer Ingelheim, and NovoNordisk. K.E. received honoraria for speaking at meetings from Novartis, Sanofi-Aventis, Lilly, AstraZeneca, Boehringer Ingelheim, and NovoNordisk. No other potential conflict of interest relevant to this article was reported.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"135"}}