{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T01:27:14Z","timestamp":1772242034465,"version":"3.50.1"},"reference-count":40,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>The ACE insertion\/deletion (I\/D) polymorphism has been widely studied in people with diabetes, albeit not with regard to lower-limb amputation (LLA). We examined associations among this polymorphism, plasma ACE concentration, and LLA in people with type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>ACE I\/D genotype and plasma ACE were assessed in three prospective cohorts of participants with type 1 diabetes. LLA was defined as minor (below-the-ankle amputation consisting of at least one ray metatarsal resection) or major (transtibial or transfemoral) amputation. Linear, logistic, and Cox regression models were computed to evaluate the likelihood of prevalent and incident LLA by ACE genotype (XD [ID or ID] vs. II) and plasma ACE, after adjusting for confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Among 1,301 participants (male 54%, age 41 \u00b1 13 years), 90 (6.9%) had a baseline history of LLA. Baseline LLA was more prevalent in XD (7.4%) than in II genotype (4.5%, odds ratio [OR] 2.17 [95 %CI 1.03\u20134.60]). Incident LLA occurred in 53 individuals during the 14-year follow-up and was higher in XD versus II carriers (hazard ratio 3.26 [95% CI 1.16\u201313.67]). This association was driven by excess risk of minor, but not major, LLA. The D allele was associated with increased prevalent LLA at the end of follow-up (OR 2.48 [1.33\u20134.65]). LLA was associated with higher mean (95% CI) ACE levels in II (449 [360, 539] vs. 354 [286, 423] ng\/mL), but not XD (512 [454, 570] vs. 537 [488, 586]), carriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>This report is the first of an independent association between ACE D allele and excess LLA risk, mainly minor amputations, in patients with type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc21-0973","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T11:27:52Z","timestamp":1638358072000},"page":"407-415","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":5,"title":["Association Between the\n                    <i>ACE<\/i>\n                    Insertion\/Deletion Polymorphism and Risk of Lower-Limb Amputation in Patients With Long-Standing Type 1 Diabetes"],"prefix":"10.2337","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6139-1197","authenticated-orcid":false,"given":"Kamel","family":"Mohammedi","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Nutrition, Bordeaux University Hospital, H\u00f4pital Haut-L\u00e9v\u00eaque, Pessac, France"},{"name":"Faculty of Medicine, University of Bordeaux, Bordeaux, France"},{"name":"Biology of Cardiovascular Diseases, INSERM U1034, Pessac, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yawa","family":"Abouleka","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Universit\u00e9 de Paris, Sorbonne Universit\u00e9, Paris, France"},{"name":"Service d\u2019Endocrinologie Diab\u00e9tologie Nutrition, H\u00f4pital Bichat, AP-HP, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlyne","family":"Carpentier","sequence":"additional","affiliation":[{"name":"Service d\u2019Endocrinologie Diab\u00e9tologie Nutrition, CHU d\u2019Angers, Angers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Potier","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Universit\u00e9 de Paris, Sorbonne Universit\u00e9, Paris, France"},{"name":"Service d\u2019Endocrinologie Diab\u00e9tologie Nutrition, H\u00f4pital Bichat, AP-HP, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Severine","family":"Dubois","sequence":"additional","affiliation":[{"name":"Service d\u2019Endocrinologie Diab\u00e9tologie Nutrition, CHU d\u2019Angers, Angers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ninon","family":"Foussard","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Nutrition, Bordeaux University Hospital, H\u00f4pital Haut-L\u00e9v\u00eaque, Pessac, France"},{"name":"Faculty of Medicine, University of Bordeaux, Bordeaux, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Rigalleau","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Nutrition, Bordeaux University Hospital, H\u00f4pital Haut-L\u00e9v\u00eaque, Pessac, France"},{"name":"Faculty of Medicine, University of Bordeaux, Bordeaux, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Fran\u00e7ois","family":"Gautier","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Universit\u00e9 de Paris, Sorbonne Universit\u00e9, Paris, France"},{"name":"Service de Diab\u00e9tologie et d\u2019Endocrinologie, H\u00f4pital Lariboisi\u00e8re, AP-HP, Universit\u00e9 de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Gourdy","sequence":"additional","affiliation":[{"name":"Service d\u2019Endocrinologie Diab\u00e9tologie Nutrition, CHU de Toulouse, Toulouse, France"},{"name":"Institut des Maladies M\u00e9taboliques et Cardiovasculaires, UMR1297 INSERM\/UPS, Universit\u00e9 Toulouse 3, Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Charpentier","sequence":"additional","affiliation":[{"name":"10Center for Study and Research for Improvement of the Treatment of Diabetes, Bioparc-G\u00e9nopole \u00c9vry-Corbeil, \u00c9vry, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronan","family":"Roussel","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Universit\u00e9 de Paris, Sorbonne Universit\u00e9, Paris, France"},{"name":"Service d\u2019Endocrinologie Diab\u00e9tologie Nutrition, H\u00f4pital Bichat, AP-HP, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Scheen","sequence":"additional","affiliation":[{"name":"11CHU Li\u00e8ge, Li\u00e8ge Universit\u00e9, Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Bauduceau","sequence":"additional","affiliation":[{"name":"12Service d\u2019Endocrinologie, H\u00f4pital B\u00e9gin, Saint Mand\u00e9, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samy","family":"Hadjadj","sequence":"additional","affiliation":[{"name":"13Institut du Thorax, INSERM, CNRS, Universit\u00e9 de Nantes, CHU Nantes, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Alhenc-Gelas","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Universit\u00e9 de Paris, Sorbonne Universit\u00e9, Paris, 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