Short- and long-term treatments with iloprost in diabetic patients with peripheral vascular disease: effects on the cardiovascular risk factor plasminogen activator inhibitor type-1.
OBJECTIVE
Iloprost, an analogue of prostacyclin, is often utilised in subjects with diabetes mellitus complicated by macroangiopathy.


METHODS
The effects of iloprost infusion on plasminogen activator inhibitor type-1 (PAI-1), glucometabolic control and cardiovascular equilibrium in patients with type-2 diabetes mellitus and peripheral arterial occlusive disease were investigated. Thirteen (7 men/6 women) normal-weight, normotensive and non-smoker type-2 diabetic patients (63.8 +/- 3.4 years, mean +/- SD) with peripheral arterial occlusive disease, stage-II according to Fontaine classification, were enrolled. Eight (four men/four women) patients underwent three study designs, each separated by a 1-week interval: study I, infusion of iloprost (3 ng kg(-1) min(-1) for 5 h) for 1 day alone (short-term treatment); study II, infusion of saline (for 5 h) for 1 day (control treatment); study III, infusion of iloprost (3 ng kg(-1) min(-1) for 5 h) over a period of 28 days (long-term treatment). The remaining five (three men/two women) patients underwent study IV only, infusion of saline over a period of 28 days (placebo treatment). Plasma levels of glucose, plasminogen, PAI-1 activity and fibrinogen, blood pressure and heart rate were determined in all studies, while plasma insulin levels, blood HbA(1c), walking distance and Winsor index only in studies III and IV.


RESULTS
Both short- and long-term treatments with iloprost significantly reduced PAI-1 activity (baseline vs end: 17.4 +/- 1.9 AU/ml vs 15.0 +/- 1.6 AU/ml, P < 0.02; 20.5 +/- 7.6 AU/ml vs 7.9 +/- 2.1 AU/ml, P < 0.002, respectively). Long-term treatment with iloprost significantly increased walking distance (baseline vs end: 325 +/- 41 m vs 496 +/- 52 m, P < 0.0001), but not Winsor index. Neither glucometabolic control nor cardiovascular equilibrium were affected by short- and long-term treatments with iloprost. Control and placebo treatments did not cause any significant modifications in the parameters evaluated.


CONCLUSIONS
If confirmed by further investigations, the results of this pilot study suggest that iloprost, infused for both brief and long periods, is able to reduce the cardiovascular risk factor PAI-1, increases free walking capacity and does not affect glucometabolic control and blood pressure in type-2 diabetic patients complicated by macroangiopathy.
Cozzolino
D
D
Department of Geriatrics and Metabolic Diseases, II University of Naples, via Cozzolino 116, I-80056-Ercolano, Naples, Italy.
Coppola
L
L
Masi
S
S
Salvatore
T
T
Sasso
F C
FC
De Lucia
D
D
Gentile
S
S
Torella
R
R
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D005215:Fasting; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016285:Iloprost / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010865:Pilot Projects; D010958:Plasminogen / Q000187:drug effects / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking
D001786:Blood Glucose; D005340:Fibrinogen; D006442:Glycated Hemoglobin; D016285:Iloprost; D007328:Insulin; D010958:Plasminogen; D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors