Effect of pioglitazone on left ventricular diastolic function and fibrosis of type III collagen in type 2 diabetic patients.
BACKGROUND
Myocardial fibrosis is the major factor that regulates left ventricular (LV) diastolic function. Pioglitazone, an anti-diabetic drug, is reported to improve the LV diastolic function in diabetic patients, but its influence on myocardial fibrosis has not been clarified. We evaluated the effect of pioglitazone on LV diastolic function and myocardial fibrosis in type 2 diabetic (T2DM) patients.


RESULTS
Fifteen T2DM patients were enrolled in the ON group, and the parameters were examined before and after pioglitazone administration (15-30 mg/day) for 6 months. Twenty-four T2DM patients were assigned to the OFF group, and the parameters were examined before and 6 months after cessation of pioglitazone. We measured echocardiographic parameters such as early diastolic mitral annular velocity (E') and plasma concentration of aminoterminal propeptide of procollagen type III (PIIIP), a marker of myocardial fibrosis. In the ON group, pioglitazone significantly increased E' (6.04+/-1.70 cm/s vs. 6.51+/-1.64 cm/s, p<0.01) and decreased PIIIP (0.553+/-0.056 U/ml vs. 0.517+/-0.072 U/ml, p<0.05). There was a significant negative correlation between the change in PIIIP and the change in E' (r=-0.424, p=0.046). On the other hand, E' was significantly decreased (5.69+/-1.34 cm/s vs. 4.97+/-1.20 cm/s, p<0.01) in the OFF group. PIIIP was not significantly changed in the OFF group, but there was a significant negative correlation between the change in PIIIP and the change in E' (r=-0.374, p=0.035).


CONCLUSIONS
Six months of pioglitazone administration suppressed the synthesis of type III collagen, and this was associated with improved LV diastolic function in T2DM patients. Cessation of pioglitazone weakened the suppression of the synthesis of type III collagen, which in turn seemed to be associated with worse LV diastolic function.
Terui
Gen
G
Department of Cardiovascular Medicine, Akita Red Cross Hospital, Kamikitate Saruta, Aza-Naeshirosawa 222-1, Akita, Akita 010-1495, Japan. gterui@archosp-1998.com
Goto
Takashi
T
Katsuta
Mitsuaki
M
Aoki
Isamu
I
Ito
Hiroshi
H
D000368:Aged; D015415:Biomarkers / Q000097:blood; D024061:Collagen Type III / Q000096:biosynthesis* / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology*; D003971:Diastole / Q000187:drug effects; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D015415:Biomarkers; D024061:Collagen Type III; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone