Beneficial effect of troglitazone, an insulin-sensitizing antidiabetic agent, on coronary circulation in patients with non-insulin-dependent diabetes mellitus.
Evidence is increasing for small vessel remodeling and disturbance of endothelium-dependent vasodilation in diabetic patients. Insulin increases vascular wall thickening and produces endothelial dysfunction. Troglitazone, a new insulin-sensitizer antidiabetic agent, is considered to reduce plasma insulin level and the present study assessed its effect on the coronary circulation of the patients with non-insulin-dependent diabetes mellitus (NIDDM). Analysis of the myocardial washout rate with adenosine triphosphate-stress thallium-201 scintigraphy was used to estimate coronary circulation, and for estimation of insulin sensitivity, the homeostasis model insulin resistance index (HOMA-R) was calculated. Patients were treated with monotherapy of either troglitazone (200 mg bid, n=12) or glibenclamide (2.5 mg daily, n=12) for 3 months. Age-, sex- and risk factors-matched subjects without NIDDM were employed as a control. Fasting plasma glucose and hemoglobin A1c were similarly decreased by troglitazone or glibenclamide. Plasma insulin level (pmol/L) decreased from 66.6+/-10.8 to 39.0+/-7.2 with troglitazone, but was unchanged by glibenclamide (58.8+/-7.2 to 66.0+/-10.8). The diabetic groups had a significantly lower washout rate than controls, which was improved by troglitazone, but not by glibenclamide. In addition, the increase in washout rate correlated significantly with the decrease in HOMA-R in the troglitazone group. In conclusion, troglitazone can restore coronary circulation by improving insulin resistance in patients with NIDDM.
Sekiya
M
M
Department of Cardiology, Ehime National Hospital, Onsen-gun, Japan. msekiya@ehime-nh.go.jp
Suzuki
J
J
Watanabe
K
K
Funada
J
J
Otani
T
T
Akutsu
H
H
D000255:Adenosine Triphosphate / Q000008:administration & dosage; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D016022:Case-Control Studies; D002839:Chromans / Q000008:administration & dosage* / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D013794:Thallium Radioisotopes / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage* / Q000494:pharmacology; D045162:Thiazolidinediones; D000077288:Troglitazone; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D000255:Adenosine Triphosphate; D001786:Blood Glucose; D002839:Chromans; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D013794:Thallium Radioisotopes; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone; D014665:Vasodilator Agents