|ISSN No. 1606-7754 Vol.16 No.1 April 2008|
Effects of iloprost (a prostacyclin analogue) on the endothelial dysfunction and foot ulcers in diabetic patients with peripheral arterial disease
Murat Sert1, Baris Soydas1, Kairgeldy Aikimbaev2, Tamer Tetiker2
Faculty of Medicine Departments of Internal Medicine, Division of Endocrinology1 and Department of Radiology2 Cukurova University, Adana, Turkey
Objectives: To asses the efficiency of iloprost (an analogue of prostacyclin) infusion on endothelial functions and amputation rate in diabetic foot ulcers with complicated macroangiopathy. Material and Methods: Sixty (36 men / 24 women) type 2 diabetic patients (61.8 ± 9.7 years, mean ±SD) with diabetic foot ulcer and peripheral arterial occlusive disease, stage III or more by Wagner classification, and 15 (9 male/ 6 female) healthy controls (60.7 ± 9.1 years, mean ±SD) were enrolled in the study. Thirty patients (group I) had iloprost infusion (0.5-2 ng/kg/min for 6 h) for 10 consecutive days. Endothelial functions were determined by brachial arterial flow mediated dilation (FMD) method at stage 0 (basal), 10th and 30th days. Group II patients (n=30) were treated in the same manner as group I except iloprost treatment constituting a patient control group. Results: Group I patients showed a significant improvement in the endothelial functions at 10th day, and 30th day (p=0.002) in respect to group II . There were no differences between group I and group II regarding the hospitalization period and amputation rates. Iloprost was well tolerated. Three patients had adverse reactions such as maculo-papular skin eruptions, itching, hypotension and dyspnea due to iloprost infusion; one completed the treatment and 2 had to discontinue the iloprost infusion. Conclusion: Ten-day iloprost infusion therapy to patients with diabetic foot ulcers seems to be efficient in the improvement of endothelial function, but, despite our positive clinical observation, this improvement does not affect the outcome of the amputation rates at 30 days follow up period.
Key Words: Diabetes mellitus, Endothelium function, Foot ulcers, Prostacyclin
Diabetic foot is one of the important causes of morbidity in diabetes mellitus.1,2 It is caused by ulcerations due to neuropathic and ischemic changes, which are frequently complicated by infections.1,2 Foot ulcers occur in 5% of the diabetic population and up to 3% will have a lower limb amputation.3 The presence or absence of infection and/or ischemia, footwear and pressure relief, and overall glycemic control influence the healing of ulcers.4
The first-line treatment for occlusive disease at the stage of chronic severe ischaemia consists of revascularization by means of surgery or transluminal angioplasty. However, such revascularization cannot be carried out in 39% of general cases5 and in particular in diabetic patients, who constitute about 45% of all lower extremity amputations cases.6
Endothelial dysfunction is thought to be an important factor in the development of atherosclerosis, hypertension, and heart failure. Over the past decade, a noninvasive technique has evolved to evaluate flow-mediated vasodilatation (FMD), an endothelium-dependent function in the brachial artery.7,8 This stimulus provokes the endothelium to release nitric oxide (NO) with subsequent vasodilatation that can be imaged and quantified as an index of vasomotor function. This technique is attractive because it is noninvasive and allows repeated measurements. However, despite its widespread use, there are technical and interpretive limitations.
Iloprost, a novel analogue of prostacyclin (PGI2), with similar potent vasodilating and anti-platelet properties but with less hypotensive action, has been shown to exert beneficial effects when infused in patients affected by ischemic vascular disease.9 Improvement in walking distance and decrease in major amputation rates were observed in both diabetic and non-diabetic subjects following treatment with iloprost.10
This study was designed to examine the effects of 10 days iloprost administration on endothelial functions and the foot amputation rates in diabetic patients with ischemic foot ulcers.