Nephro- and neuroprotective effects of rosiglitazone versus glimepiride in normoalbuminuric patients with type 2 diabetes mellitus: a randomized controlled trial

Petrică, Ligia; Petrica, Maxim; Vlad, Adrian; Jianu, Dragoș Cătălin; Gluhovschi, Gheorghe; Ianculescu, Calina; Dumitraşcu, Victor; Giju, Sorin; Gluhovschi, Cristina; Bob, Flaviu; Ursoniu, Sorin; Gădălean, Florica; Velciov, Silvia; Bozdog, Gheorghe; Marian, Roxana

doi:10.1007/s00508-009-1279-3

Cited by 30 publications

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“…In our study, the levels of urinary α 1 -microglobulin were increased in 27.9% of patients with normoalbuminuria, and there was no correlation with HbA 1c , DM duration and GFR, which is in agreement with our previous study [14]. …”

Section: Discussionsupporting

confidence: 82%

“…In our study, the levels of urinary β 2 -microglobulin were increased in 23.5% of the patients with normoalbuminuria, and there was no correlation with HbA 1c , DM duration and GFR, similar to other data reported by us in a previous study [14]. Furthermore, it is worth underlining that urinary α 1 -/β 2 -microglobulin did not correlate with plasma ADMA and UACR in our patients with type 2 DM, thus pointing to the fact that glomerular endothelial dysfunction does not parallel PT dysfunction.…”

Section: Discussionsupporting

confidence: 81%

“…In normoalbuminuric patients with type 1 and 2 DM, increased levels of tubular dysfunction biomarkers, such as urinary α 1 - [14,30,31,32] and β 2 -microglobulin [33,34], and fractional excretion of magnesium [35], support the theory that tubular functional defects precede the onset of albuminuria.…”

Section: Discussionmentioning

confidence: 82%

“…In a 1-year, open-label, randomized, controlled trial performed by us in normoalbuminuric patients with type 2 DM, the increase in α 1 -microglobulin and urinary β 2 -microglobulin preceded the occurrence of albuminuria in patients treated with glimepiride and metformin versus patients treated with rosiglitazone and metformin [14]. …”

Section: Discussionmentioning

confidence: 99%

“…A recent study in a rat model showed that PT dysfunction is responsible for the increased albumin excretion in early DN [13]. In a previous work performed by us in normoalbuminuric patients with type 2 DM enrolled in a 1-year, open-label, randomized, controlled trial, we demonstrated that PT dysfunction precedes the occurrence of albuminuria in patients treated with glimepiride and metformin versus patients treated with rosiglitazone and metformin [14]. …”

Section: Introductionmentioning

confidence: 99%

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Proximal Tubule Dysfunction Is Dissociated from Endothelial Dysfunction in Normoalbuminuric Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study

Petrică¹,

Petrica²,

Vlad³

et al. 2010

Nephron Clin Pract

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Introduction: The aim of our study was to clarify the hypothesis that proximal tubule (PT) dysfunction may be responsible for early diabetic nephropathy (DN), independently of preceding glomerular endothelial dysfunction. The pattern of endothelial dysfunction and its potential variability was evaluated in two vascular beds, the kidney and the brain. Methods: A total of 68 normoalbuminuric type 2 diabetes mellitus (DM) patients were enrolled in a cross-sectional study and the following parameters were assessed: urinary albumin:creatinine ratio (UACR), urinary α₁-microglobulin, urinary β₂-microglobulin, plasma asymmetric dimethyl-arginine (ADMA), serum creatinine, glomerular filtration rate (GFR), C-reactive protein (CRP), fibrinogen, HbA_1c; pulsatility and resistance indices in the internal carotid artery and middle cerebral artery and intima-media thickness (IMT) in the common carotid artery; cerebrovascular reactivity was evaluated through the breath-holding test. Results: Plasma ADMA was increased in 12 patients (17.5%), urinary α₁-microglobulin in 19 patients (27.9%) and urinary β₂-microglobulin in 16 patients (23.5%). Cerebral hemodynamic indices correlated with plasma ADMA, CRP, fibrinogen, duration of DM, HbA_1c and GFR. ADMA correlated with fibrinogen, CRP, HbA_1c, duration of DM and GFR. There were no correlations between ADMA and UACR, and urinary α₁-/β₂-microglobulin. Also, no correlations were found between urinary α₁-/β₂-microglobulin and UACR, HbA_1c, duration of DM and GFR. Conclusion: The increase in urinary α₁-/β₂-microglobulin precedes the stage of albuminuria. It may be assumed that early DN is related to PT dysfunction. Endothelial dysfunction plays a pivotal role in the brain vasculature, while its involvement in the development of early DN is not conditional on the occurrence of albuminuria.