Effect of troglitazone on serum γ-glutamyltransferase activity and plasma t-PA/PAI-1 complex in type 2 diabetic patients

Background: This study was conducted to determine whether troglitazone (CAS 97322-87-7, Noscal (R)), a thiazolidinedione with a-tocopherol in the side chain, had an antioxidant effect in patients with Type 2 diabetes. Methods: In 46 Type 2 diabetic outpatients aged 64 +/- 7 years (male/female: 33/13), with a body mass index of 23.4 +/- 2.8 kg/m(2), a 2-year prospective study was performed. Patients were given troglitazone tablet (200 mg) twice a day. After treatment for 4 months, troglitazone was withheld for one month (washout period). Then troglitazone was resumed for a further 19 months. Results: The study was completed in 28 patients. In 18 patients, it was not completed because of side effects in 4 female patients and because of withdrawal of troglitazone from the Japanese market in 14 patients. Fasting plasma glucose was decreased by troglitazone treatment from 170.2 +/- 38.2 mg/dl to 151.6 +/- 34.5 mg/dl (ANOVA: F = 8.054, p < 0.001). Washout caused it to return to the pre-treatment level (170.9 +/- 38.0 mg/dl), but it decreased again to 145.4 +/- 33.4 mg/dl with the resumption of treatment (F = 3.845, p < 0.001). Glycated hemoglobin was decreased by treatment from 8.2 +/- 1.6% to 7.9 +/- 1.6% (F = 7.558, p < 0.001). Washout caused it to return to the pre-treatment level (8.0 +/- 1.6%), but it decreased again to 7.6 +/- 1.2 % with the resumption of treatment (F = 1.985, p = 0.041). Fasting serum immunoreactive insulin was decreased by treatment from 5.5 +/- 3.4 mu U/ml to 4.0 +/- 2.2 mu U/ml (F = 9.098, p < 0.001). Washout caused it to return to near the pre-treatment level (4.6 +/- 2.4 mu U/ml). After resumption of treatment, it remained unchanged. Serum gamma-glutamyltransferase (gamma-GT) activity was decreased by treatment from 37.5 +/- 25.7 U/I to 25.6 +/- 12.3 U/I (F = 19.406, p < 0.001). Washout caused it to return to the pre-treatment level (36.5 +/- 25.1 U/l), but it decreased again to 24.2 +/- 10.1 U/I with the resumption of treatment (F = 7.931, p < 0.001). Plasma tissue plasminogen activator(t-PA)/plasminogen activator inhibitor-1 (PAI-1) complex was decreased by treatment from 21.7 +/- 8.6 ng/ml to 19.0 +/- 6.6 ng/ml (F = 8.784, p < 0.001). Washout caused it to return to the pretreatment level (21.9 +/- 7.4 ng/ml), but it decreased again to 14.3 +/- 4.3 ng/ml after the resumption of treatment (F = 12.341, P < 0.001). Conclusion: Decreases in serum gamma-GT activity and plasma t-PA/PAI-I complex were closely related with antioxidant action of troglitazone.