LONG-TERM TREATMENT WITH THE DUAL ANTITHROMBOXANE AGENT PICOTAMIDE DECREASES MICROALBUMINURIA IN NORMOTENSIVE TYPE-2 DIABETIC-PATIENTS

Picotamide both inhibits thromboxane synthetase and acts as a thrombox ane antagonist at the receptor level. We investigated the long-term ef fect of picotamide on urinary albumin excretion (UAE) at rest and indu ced by exercise in 30 type 2 diabetic patients who were normotensive a nd had microalbuminuria while at rest. The subjects of our study had a mean age of 52.5 +/- 1.6 years, BMI of 28.5 +/- 0.7 kg/m(2), diabetes duration of 9.1 +/- 1.8 years, and HbA(1c),, of 7.0 +/- 0.8%. The stu dy was a randomized double-blind placebo-controlled trial. The patient s were randomly allocated to receive for 1 year either picotamide, 300 mg, 3 tablets/day, or placebo, 3 tablets/day. The patients were asked to visit our out-patient clinic after 1, 3, 6, 9, and 12 months of tr eatment. At all times, blood pressure, microalbuminuria at rest, blood glucose, serum creatinine, serum picotamide, and creatinine clearance were measured; at baseline and after 6 and 12 months, all patients un derwent submaximal physical exercise. After 6 months of picotamide, ba seline and exercise-induced microalbuminuria were significantly decrea sed (up to one-third) as compared with the baseline and placebo level, with no further drops at month 12 of picotamide treatment. On placebo treatment, UAE at rest and after exercise was slightly increased comp ared with baseline values. The effects of picotamide occurred without significant side effects or changes in either blood pressure levels or glycometabolic control. Our study is the first long-term intervention trial in type 2 diabetes showing that an antithromboxane agent is abl e to decrease microalbuminuria, which in this disease is a dual marker of macro-and microangiopathy. Our findings suggest an important role for thromboxane in the pathophysiology of microalbuminuria in diabetes ; moreover, we hypothesize that antithromboxane agents may have a plac e in the treatment/prevention of both macro-and microvascular complica tions in type 2 diabetic patients.