Pioglitazone delays proximal tubule dysfunction and improves cerebral vessel endothelial dysfunction in normoalbuminuric people with type 2 diabetes mellitus

Aim: The renal and cerebral protective effects of pioglitazone were assessed in normoalbuminuric patients with type 2 diabetes mellitus (DM).

Methods: A total of 68 normoalbuminuric type 2 DM patients were enrolled in a one-year open-label randomized controlled trial: 34 patients (pioglitazone-metformin) vs. 34 patients (glimepiride-metformin). All patients were assessed concerning urinary albumin: creatinine ratio (UACR), urinary alpha1-microglobulin, urinary beta2-microglobulin, plasma asymmetric dymethyl-arginine (ADMA), GFR, hsC-reactive protein, fibrinogen, HbA1c; pulsatility index, resistance index in the internal carotid artery and middle cerebral artery, intima-media thickness in the common carotid artery; cerebrovascular reactivity was evaluated through the breath-holding test.

Results: At 1 year there were differences between groups regarding ADMA, urinary beta2-microglobulin, urinary alpha1-microglobulin, parameters of inflammation, serum creatinine, GFR, UACR, the cerebral haemodynamic indices. Significant correlations were found between alpha 1-microglobulin-UACR (R(2)=0.143; P=0.001) and GFR (R(2)=0.081; P=0.01); beta2-microglobulin-UACR (R(2)=0.241; P=0.0001) and GFR (R(2)=0.064; P=0.036); ADMA-GFR (R(2)=0.338; P=0.0001), parameters of inflammation, HbA1c, duration of DM, cerebral indices. There were no correlations between ADMA-UACR, urinary alpha1-microglobulin and beta2-microglobulin.

Conclusion: Proximal tubule (PT) dysfunction precedes albuminuria and is dissociated from endothelial dysfunction in patients with type 2 DM. Pioglitazone delays PT dysfunction and improves cerebral vessels endothelial dysfunction in normoalbuminuric patients with type 2 DM.