{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:05:09Z","timestamp":1790611509583,"version":"4.1.0"},"reference-count":30,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,9,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers.<\/jats:p>\n                  <jats:p>RESEARCH DESIGN AND METHODS\u2014A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5,000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1) who healed with intact skin; 2) in whom the study ulcer was improved, unchanged, or impaired; or 3) who were amputated above or below the ankle level, as compared with control subjects.<\/jats:p>\n                  <jats:p>RESULTS\u2014Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided \u03c72 test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area \u226550% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased \u226550%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 \u00b1 8 weeks in the dalteparin group compared with 16 \u00b1 7 weeks in placebo group (NS).<\/jats:p>\n                  <jats:p>CONCLUSIONS\u2014The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.<\/jats:p>","DOI":"10.2337\/diacare.26.9.2575","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T17:51:27Z","timestamp":1173117087000},"page":"2575-2580","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":56,"title":["Effect of Dalteparin on Healing of Chronic Foot Ulcers in Diabetic Patients With Peripheral Arterial Occlusive Disease"],"prefix":"10.2337","volume":"26","author":[{"given":"Majid","family":"Kalani","sequence":"first","affiliation":[{"name":"Department of Cardiology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Apelqvist","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital in Malmo\u0308, University of Lund, Malmo\u0308, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Blomba\u0308ck","sequence":"additional","affiliation":[{"name":"Deparment of Surgical Sciences\/Coagulation Research, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Brismar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjo\u0308rn","family":"Eliasson","sequence":"additional","affiliation":[{"name":"Diabetes Center, Sahlgrenska University Hospital, Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan W.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital in Umea\u030a, Umea\u030a, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Fagrell","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Hamsten","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden"},{"name":"Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Torffvit","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital in Lund, University of Lund, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun","family":"Jo\u0308rneskog","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031215085136600_R1","doi-asserted-by":"crossref","unstructured":"Apelqvist J, Ragnarson Tennvall G, Persson U, Larsson J: Diabetic foot ulcers in a multidisciplinary setting: an economical analysis of primary healing or healing with amputation. J Intern Med\u2008235: 463\u2013471, 1994","DOI":"10.1111\/j.1365-2796.1994.tb01104.x"},{"key":"2022031215085136600_R2","unstructured":"Apelqvist J: Diabetic Foot Ulcers: The Importance of Clinical Characteristics and Prognostic Factors for the Outcome. Dissertation. Lund, Sweden, University of Lund, 1991"},{"key":"2022031215085136600_R3","doi-asserted-by":"crossref","unstructured":"Boulton AJM, Connor H, Cavanagh PR: The Foot in Diabetes. 3rd ed. Chichester, U.K., Wiley, 2000","DOI":"10.1002\/0470846399"},{"key":"2022031215085136600_R4","doi-asserted-by":"crossref","unstructured":"Zimny S, Dessel F, Ehren M, Pfohl M, Schatz H: Early detection of microcirculatory impairment in diabetic patients with foot at risk. Diabetes Care\u200824: 1810\u20131814, 2001","DOI":"10.2337\/diacare.24.10.1810"},{"key":"2022031215085136600_R5","doi-asserted-by":"crossref","unstructured":"Jo\u0308rneskog G, Brismar K, Fagrell B: Skin capillary circulation is more impaired in toes of diabetic than non-diabetic patients with peripheral vascular disease. Diabet Med\u200812: 36\u201341, 1995","DOI":"10.1111\/j.1464-5491.1995.tb02059.x"},{"key":"2022031215085136600_R6","unstructured":"Jo\u0308rneskog G, Brismar K, Fagrell B: Low molecular weight heparin seems to improve local capillary circulation and healing of chronic foot ulcers in diabetic patients. VASA\u20082: 137\u2013142, 1993"},{"key":"2022031215085136600_R7","doi-asserted-by":"crossref","unstructured":"Wagner FW: The dysvascular foot: a system for diagnosis and treatment. Foot Ankle\u20082: 64\u2013122, 1981","DOI":"10.1177\/107110078100200202"},{"key":"2022031215085136600_R8","doi-asserted-by":"crossref","unstructured":"Rith-Najarian SJ, Stolusky T, Gohdes DM: Identifying patients at high risk for lower-extremity amputations in a primary health care setting: a prospective evaluation of simple screening criteria. Diabetes Care\u200815: 1386\u20131389, 1992","DOI":"10.2337\/diacare.15.10.1386"},{"key":"2022031215085136600_R9","unstructured":"Pa\u030ahlsson H-I, Wahlberg E, Wei SZ, Jo\u0308rneskog G, Swedenborg J, Olofsson P, Fagrell B: Toe blood pressure measurements with laser Doppler fluxmetry. J Vasc Invest\u20082: 82\u201386, 1996"},{"key":"2022031215085136600_R10","doi-asserted-by":"crossref","unstructured":"Apelqvist J, Castenfors J, Larsson J, Stenstro\u0308m A, Agardh CD: Prognostic value of systolic ankle and toe blood pressure levels in outcome of diabetic foot ulcer. Diabetes Care\u200812: 373\u2013378, 1989","DOI":"10.2337\/diacare.12.6.373"},{"key":"2022031215085136600_R11","doi-asserted-by":"crossref","unstructured":"Apelqvist J, Larsson J, Agardh CD: The importance of peripheral pulses, peripheral oedema and local pain in the outcome of diabetic foot ulcers. Diabet Med\u20087: 590\u2013594, 1990","DOI":"10.1111\/j.1464-5491.1990.tb01454.x"},{"key":"2022031215085136600_R12","doi-asserted-by":"crossref","unstructured":"Kalani M, Brismar K, Fagrell B, O\u0308stergren J, Jo\u0308rneskog G: Transcutaneous oxygen tension and toe blood pressure as predictors for outcome of diabetic foot ulcers. Diabetes Care\u200822: 147\u2013151, 1999","DOI":"10.2337\/diacare.22.1.147"},{"key":"2022031215085136600_R13","doi-asserted-by":"crossref","unstructured":"Assal JP, Muhlhauser I, Pernet A, Gfeller R, Jorgens V, Berger M: Patient education as the basis for diabetes care in clinical practice. Diabetologia\u200828: 602\u2013613, 1985","DOI":"10.1007\/BF00281995"},{"key":"2022031215085136600_R14","doi-asserted-by":"crossref","unstructured":"Falkenberg M: Metabolic control and amputations among diabetics in primary health care: a population-based intensified programme governed by patient education. Scand J Prim Health Care\u20088: 25\u201329, 1990","DOI":"10.3109\/02813439008994925"},{"key":"2022031215085136600_R15","doi-asserted-by":"crossref","unstructured":"Larsson J, Apelqvist J, Agardh CD, Stenstro\u0308m A: Decreasing incidence of major amputation in diabetic patients: a consequence of a multidisciplinary foot care team approach? Diabet Med\u200812: 770\u2013776, 1995","DOI":"10.1111\/j.1464-5491.1995.tb02078.x"},{"key":"2022031215085136600_R16","unstructured":"Eneroth M: Amputation for Vascular Disease: Prognostic Factors for Healing, Long-Term Outcome and Costs. Dissertation. Lund, Sweden, Lund University Hospital, 1997"},{"key":"2022031215085136600_R17","doi-asserted-by":"crossref","unstructured":"Eliasson B, Attvall S, Taskinen MR, Smith U: Smoking cessation improves insulin sensitivity in healthy middle-aged men. Eur J Clin Invest\u200827: 450\u2013456, 1997","DOI":"10.1046\/j.1365-2362.1997.1330680.x"},{"key":"2022031215085136600_R18","doi-asserted-by":"crossref","unstructured":"Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med\u2008329: 977\u2013986, 1993","DOI":"10.1056\/NEJM199309303291401"},{"key":"2022031215085136600_R19","doi-asserted-by":"crossref","unstructured":"Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ\u200812: 405\u2013412, 2000","DOI":"10.1136\/bmj.321.7258.405"},{"key":"2022031215085136600_R20","doi-asserted-by":"crossref","unstructured":"Margolis DJ, Kantor J, Berlin JA: Healing of diabetic neuropathic foot ulcers receiving standard treatment: a meta-analysis. Diabetes Care\u200822: 692\u2013695, 1999","DOI":"10.2337\/diacare.22.5.692"},{"key":"2022031215085136600_R21","doi-asserted-by":"crossref","unstructured":"Apelqvist J: Wound healing in diabetes: outcome and costs. Clin Podiatr Med Surg\u200815: 21\u201339, 1998","DOI":"10.1016\/S0891-8422(23)01026-1"},{"key":"2022031215085136600_R22","doi-asserted-by":"crossref","unstructured":"Apelqvist J, Castenfors J, Larsson J, Stenstro\u0308m A, Agardh CD: Wound classification is more important than site of ulceration in the outcome of diabetic foot ulcers. Diabet Med\u20086: 526\u2013530, 1989","DOI":"10.1111\/j.1464-5491.1989.tb01221.x"},{"key":"2022031215085136600_R23","unstructured":"Ljungberg B: On Heparin and Low Molecular Weight Heparin, Clinical and Experimental Studies. Dissertation. Stockholm, Sweden, Karolinska Institute, 1988"},{"key":"2022031215085136600_R24","doi-asserted-by":"crossref","unstructured":"Schulman S, Granqvist S, Wiman B, Lockner D: Thrombosis and fibrinolytic parameters during heparin treatment of deep vein thrombosis. Thromb Res\u200839: 607\u2013612, 1985","DOI":"10.1016\/0049-3848(85)90240-3"},{"key":"2022031215085136600_R25","doi-asserted-by":"crossref","unstructured":"Downing LJ, Strieter RM, Kadell AM, Wilke CA, Greenfield LJ, Wakefield TW: Low-dose low-molecular-weight heparin is anti-inflammatory during venous thrombosis. J Vasc Surg\u200828: 848\u2013854, 1998","DOI":"10.1016\/S0741-5214(98)70060-6"},{"key":"2022031215085136600_R26","doi-asserted-by":"crossref","unstructured":"Edmondson RA, Cohen AT, Das SK, Wagner MB, Kakkar VV: Low molecular weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting. Lancet\u2008344: 914\u2013918, 1994","DOI":"10.1016\/S0140-6736(94)92269-1"},{"key":"2022031215085136600_R27","doi-asserted-by":"crossref","unstructured":"Fujita M, Sasayama S, Asanoi H, Nakajima H, Sakai O, Ohno A: Improvement of treadmill capacity and collateral circulation as a result of exercise with heparin pretreatment in patients with effort angina. Circulation\u200877: 1022\u20131029, 1988","DOI":"10.1161\/01.CIR.77.5.1022"},{"key":"2022031215085136600_R28","doi-asserted-by":"crossref","unstructured":"Fujita M: Heparin and angiogenic therapy. Eur Heart J\u200821: 270\u2013274, 2000","DOI":"10.1053\/euhj.1999.1700"},{"key":"2022031215085136600_R29","doi-asserted-by":"crossref","unstructured":"Hehenberger K, Kratz G, Hansson A, Brismar K: Fibroblasts derived from human chronic diabetic wounds have a decreased proliferation rate, which is recovered by the addition of heparin. J Dermatol Sci\u200816: 144\u2013151, 1998","DOI":"10.1016\/S0923-1811(97)00042-X"},{"key":"2022031215085136600_R30","doi-asserted-by":"crossref","unstructured":"Kratz G, Back M, Arnander C, Larm O: Immobilised heparin accelerates the healing of human wounds in vivo. Scand J Plast Reconstr Hand Surg\u200832: 381\u2013385, 1998","DOI":"10.1080\/02844319850158462"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/26\/9\/2575\/665150\/dc0903002575.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/26\/9\/2575\/665150\/dc0903002575.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,11]],"date-time":"2024-02-11T08:08:35Z","timestamp":1707638915000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/26\/9\/2575\/22578\/Effect-of-Dalteparin-on-Healing-of-Chronic-Foot"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9,1]]},"references-count":30,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2003,9,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diacare.26.9.2575","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9,1]]}}}