Effect of troglitazone on serum gamma-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), a thiazolidinedione with alpha-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/m2, 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, D < 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 pU/ml to 4.0 +/- 2.2 pU/ml (F = 9.098, p < 0.001). Washout caused it to return to near the pre-treatment level (4.6 +/- 2.4 pU/ml). After resumption of treatment, it remained unchanged. Serum n-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/I), but it decreased again to 24.2 +/- 10.1 U/l 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).


CONCLUSIONS
Decreases in serum gamma-GT activity and plasma t-PA/PAI-1 complex were closely related with antioxidant action of troglitazone.
Koh
Hideki
H
Division of Diabetes and Metabolism, Department of Internal Medicine, Mita Hospital, International University of Health and Welfare, Tokyo, Japan.
Akiyama
Yoshitaka
Y
Yui
Katsumasa
K
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000975:Antioxidants; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000097:blood*; D000077288:Troglitazone; D005723:gamma-Glutamyltransferase / Q000097:blood*
D000410:Alanine Transaminase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D001663:Bilirubin; D001786:Blood Glucose; D002097:C-Reactive Protein; D002839:Chromans; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D045162:Thiazolidinediones; D010959:Tissue Plasminogen Activator; D000077288:Troglitazone; D005723:gamma-Glutamyltransferase