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

作者：Petrica Ligia; Vlad A^*; Petrica M; Jianu C D; Gluhovschi Gh; Gadalean Florica; Dumitrascu V; Ianculescu Calina; Firescu Catalina; Giju S; Gluhovschi Cristina; Bob F; Velciov Silvia; Bozdog Gh; Milas Oana; Marian Roxana; Ursoniu S

来源：Diabetes Research and Clinical Practice, 2011, 94(1): 22-32.

DOI：10.1016/j.diabres.2011.05.032

• Proximal tubule
• Endothelial dysfunction
• Albuminuria
• Pioglitazone

Aim: The renal and cerebral protective effects of pioglitazone were assessed in normoal-buminuric 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. Key words: proximal tubule; endothelial dysfunction, albuminuria; pioglitazone.

• 出版日期2011-10