title: Pioglitazone delays proximal tubule dysfunction and improves cerebral vessel endothelial dysfunction in normoalbuminuric people with type 2 diabetes mellitus.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Nephrology, Victor Babes University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania. ligiapetrica@rdslink.ro
authors: Ligia
authors: L
authors: Petrica
authors: A
authors: A
authors: Vlad
authors: M
authors: M
authors: Petrica
authors: C D
authors: CD
authors: Jianu
authors: Gh
authors: G
authors: Gluhovschi
authors: Florica
authors: F
authors: Gadalean
authors: V
authors: V
authors: Dumitrascu
authors: Calina
authors: C
authors: Ianculescu
authors: Catalina
authors: C
authors: Firescu
authors: S
authors: S
authors: Giju
authors: Cristina
authors: C
authors: Gluhovschi
authors: F
authors: F
authors: Bob
authors: Silvia
authors: S
authors: Velciov
authors: Gh
authors: G
authors: Bozdog
authors: Oana
authors: O
authors: Milas
authors: Roxana
authors: R
authors: Marian
authors: S
authors: S
authors: Ursoniu
mesh_terms: D000419:Albuminuria / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone