Effects of troglitazone on collagen accumulation and distensibility of aortic wall in prestage of non-insulin-dependent diabetes mellitus of Otsuka Long-Evans Tokushima Fatty rats

We investigated the effect of troglitazone (TG) on aortic distensibility an d histopathology at the preclinical stage in the non-insulin-dependent diab etes mellitus (NIDDM) model. Twenty male diabetic and 20 male nondiabetic r ats were each divided into two groups: treated-DM, untreated-DM, treated-no nDM, and untreated-nonDM. TG (0.2%) was mixed in chow in the treated groups . From age 5 to 15 weeks, fast blood glucose and insulin were monitored. At 15 weeks, oral glucose tolerance test results, aortic wall histopathology, and collagen content were studied, and intravascular ultrasound images and aortic pressure were recorded. Aortic diameter was measured during the car diac cycle, and the stiffness parameter beta was calculated. Blood glucose (mg/dl) 2 h after loading in treated-DM (139 +/- 20) was normalized (untrea ted-DM, 188 +/- 27; p < 0.05). Insulin concentration (ng/ml) in treated-DM (3.2 +/- 0.4) was lower than that in untreated-DM (8.1 +/- 1.5; p < 0.01). At 15 weeks, beta in untreated-DM (2.4 +/- 0.8) was larger than those in un treated-nonDM (1.5 +/- 0.4; p < 0.0001) and in treated-DM (1.9 +/- 0.4, p = 0.0081). Aortic wall collagen (mg/g dry weight) increased in untreated-DM (32.8 +/- 3.3) as compared with treated-DM (28.1 +/- 3.8; p = 0.048). Histo morphometry showed decreased medial area (mm(2)) in treated-DM (0.55 +/- 0. 05) compared with untreated-DM (0.78 +/- 0.12; p < 0.0001). This study sugg ests that TG may prevent metabolic abnormalities and the deterioration of a ortic distensibility at an early prediabetic stage.