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

• Published in: Diabetes research and clinical practice Vol. 94; no. 1; pp. 22 - 32
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01-10-2011
• Subjects: Albuminuria; Albuminuria - drug therapy; Albuminuria - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Endocrinology & Metabolism; Endothelial dysfunction; Endothelium, Vascular - drug effects; Female; Humans; Hypoglycemic Agents - therapeutic use; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - pathology; Male; Middle Aged; Pioglitazone; Proximal tubule; Thiazolidinediones - therapeutic use; Endothelial dysfunction; Proximal tubule; Albuminuria; Pioglitazone
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/j.diabres.2011.05.032

Abstract 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 ( R2 = 0.143; P = 0.001) and GFR ( R2 = 0.081; P = 0.01); beta2-microglobulin-UACR ( R2 = 0.241; P = 0.0001) and GFR ( R2 = 0.064; P = 0.036); ADMA–GFR ( R2 = 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.