INFLUENCE OF METABOLIC CONTROL ON THROMBOXANE BIOSYNTHESIS AND PLASMAPLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

We have previously shown that tight metabolic control by insulin thera py reduced thromboxane-dependent platelet activation in noninsulin-dep endent diabetes mellitus (NIDDM) patients. The present study was under taken to determine whether a similar effect could be obtained without switching diabetics in secondary failure to insulin treatment. For thi s purpose, we gave strict diet and exercise advise program and adjuste d on a weekly basis the oral antidiabetic therapy (glipizide) that 26 patients with NIDDM had been given over the previous months. Basal mea surements of urinary 11-dehydro-TXB(2) and PAI-1 confirmed previous fi ndings of enhanced levels of these parameters in NIDDM patients with m acrovascular disease in comparison to age- and sex-matched controls. A fter 2-6 weeks, 16 patients achieved tight metabolic control associate d with significant reduction of both thromboxane biosynthesis and PAI- 1 levels; 10 patients remained in poor control and no significant decr ease of both parameters was observed. We conclude that reduction of in -vivo platelet activation and PAI-1 antigen levels after metabolic imp rovement obtained by frequent reassessment of sulphonylurea therapy to gether with strict diet and exercise programs may have beneficial effe cts on the progression of diabetic micro- and macrovascular disease.