{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:54:41Z","timestamp":1777398881249,"version":"3.51.4"},"reference-count":28,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":3240,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,11,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>We examined the role of vascular function and inflammation in the development and failure to heal diabetic foot ulcers (DFUs). We followed 104 diabetic patients for a period of 18.4 \u00b1 10.8 months. At the beginning of the study, we evaluated vascular reactivity and serum inflammatory cytokines and growth factors. DFUs developed in 30 (29%) patients. DFU patients had more severe neuropathy, higher white blood cell count, and lower endothelium-dependent and -independent vasodilation in the macrocirculation. Complete ulcer healing was achieved in 16 (53%) patients, whereas 13 (47%) patients did not heal. There were no differences in the above parameters between the two groups, but patients whose ulcers failed to heal had higher tumor necrosis factor-\u03b1, monocyte chemoattractant protein-1, matrix metallopeptidase 9 (MMP-9), and fibroblast growth factor 2 serum levels when compared with those who healed. Skin biopsy analysis showed that compared with control subjects, diabetic patients had increased immune cell infiltration, expression of MMP-9, and protein tyrosine phosphatase-1B (PTP1B), which negatively regulates the signaling of insulin, leptin, and growth factors. We conclude that increased inflammation, expression of MMP-9, PTP1B, and aberrant growth factor levels are the main factors associated with failure to heal DFUs. Targeting these factors may prove helpful in the management of DFUs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db12-0227","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T05:59:02Z","timestamp":1339480742000},"page":"2937-2947","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":301,"title":["Mechanisms Involved in the Development and Healing of Diabetic Foot Ulceration"],"prefix":"10.2337","volume":"61","author":[{"given":"Thanh","family":"Dinh","sequence":"first","affiliation":[{"name":"Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Francesco","family":"Tecilazich","sequence":"additional","affiliation":[{"name":"Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Antonios","family":"Kafanas","sequence":"additional","affiliation":[{"name":"Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}]},{"given":"John","family":"Doupis","sequence":"additional","affiliation":[{"name":"Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Charalambos","family":"Gnardellis","sequence":"additional","affiliation":[{"name":"Technological Educational Institute of Messolonghi, Messolonghi, Greece"}]},{"given":"Ermelindo","family":"Leal","sequence":"additional","affiliation":[{"name":"Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Ana","family":"Tellechea","sequence":"additional","affiliation":[{"name":"Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Leena","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Thomas E.","family":"Lyons","sequence":"additional","affiliation":[{"name":"Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}]},{"given":"John M.","family":"Giurini","sequence":"additional","affiliation":[{"name":"Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 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