Rosiglitazone improves diastolic myocardial dysfunction in patients with type 2 diabetes mellitus

Aims: The PROactive Study has demonstrated a mortality reducing effect of thiazolidindione in type 2 diabetes mellitus (D). Additionally, diastolic myocardial dysfunction as evaluated by pulsed tissue Doppler was shown to be prognostically relevant and a marker of cardiovascular outcome. Accordingly, we tested the hypothesis, that rosiglitazone (R) improves diastolic dysfunction in D patients compared to a similar metabolic control by glimepirid (G).

Methods: This randomised cross-over study investigated 12 D patients with normal systolic ventricular function on metformin monotherapy (59±13 years, HbA1c 6.8±0.8%) before and after 4 months additional therapy with R (8mg) and with G (3mg) in the fasting state and 2 hours after a standardised breakfast (48g carbohydrates). In addition to traditional echocardiography, global left ventricular function was assessed as systolic (Vs) and diastolic myocardial velocity (Ve) averaged from 6 basal myocardial segments.

Results: With R, Ve improved significantly from 7.9.±1.7 to 8.8±1.2cm/s (p=0.04) both in the fasting and the postprandial state (p=0.04) but Vs did not. Fasting blood glucose decreased from 151±43 to 134±27mg/dl (p=0.05) and postprandial blood glucose from 196±57 to 161±51mg/dl (p=0.01). The improvement of HbA1c was not significant (7.0±1.0 to 6.8±0.8%, p=0.15). With G, there was the same reaction of HbA1c (6.7±0.6 to 6.5±0.5%, p=0.19) but no reduction of fasting (140±42 to 139±22mg/dl) or postprandial blood glucose (162±53 to 152±43mg/dl). Neither was Ve improved (8.5±1.3 to 8.3±1.6cm/s). Lipid values, blood pressure, heart rate, left ventricular and atrial size remained unchanged in both therapy regimens.

Conclusion: Additional therapy with rosiglitazone improves global diastolic myocardial function associated with improved postprandial blood glucose in patients with type 2 diabetes. This effect probably contributes to the mortality reducing effect of thiazolidindione and could be utilized as actual parameter in individual therapy control.