Nephro- and neuroprotective effects of rosiglitazone versus glimepiride in normoalbuminuric patients with type 2 diabetes mellitus: a randomized controlled trial.
BACKGROUND
Thiazolidinediones represent a novel class of drugs that exert pleiotropic effects at various levels and lower blood glucose through reduction of insulin resistance in patients with type 2 diabetes mellitus.


OBJECTIVE
The nephro- and neuroprotective effects of rosiglitazone vs. glimepiride were evaluated in normoalbuminuric patients with type 2 diabetes mellitus. The relevance of several biomarkers in the diagnosis of incipient diabetic nephropathy and cerebral microangiopathy was also assessed.


METHODS
A total of 34 normoalbuminuric patients with type 2 diabetes mellitus were enrolled in a 1-year open-label randomized controlled trial. Group A comprised 17 patients (7 men, 10 women, mean age 63 +/- 8.07 years) treated with rosiglitazone plus metformin; Group B comprised 17 patients (7 men, 10 women, mean age 63.2 +/- 7.19 years) treated with glimepiride plus metformin. All patients were assessed at initiation, at 6 months and by the end of the study concerning serum and urinary beta2-microglobulin, urinary a1-microglobulin, serum cystatin C, serum creatinine, glomerular filtration rate, C-reactive protein, fibrinogen, glycated hemoglobin, cholesterol, triglycerides, hemoglobin, and the urinary albumin/creatinine ratio (UACR). Cerebral hemodynamic parameters were also measured: pulsatility index and resistance index in the internal carotid artery and middle cerebral artery, and intima-media thickness in the common carotid artery.


RESULTS
At 1 year there were differences between groups A and B regarding serum cystatin C (P < 0.04), urinary beta2-microglobulin (P < 0.004), urinary a1-microglobulin (P < 0.0001), C-reactive protein (P < 0.0001), fibrinogen (P < 0.0001), serum creatinine (P < 0.0024), glomerular filtration rate (P < 0.0010), UACR (P < 0.0001), and the cerebral hemodynamic indices. The increase in a1- and beta2-microglobulin preceded the occurrence of microalbuminuria. UACR correlated with urinary a1- microglobulin (r = 0.4854), urinary beta2-microglobulin (r = 0.4867), and serum cystatin C (r = 0.3702). The cerebrovascular parameters improved in group A vs. group B and correlated with urinary beta2- and a1-microglobulin, C-reactive protein, fibrinogen, glomerular filtration rate, and duration of diabetes.


CONCLUSIONS
Rosiglitazone demonstrated its nephro- and neuroprotective effects in normoalbuminuric patients with type 2 diabetes mellitus by the end of the follow-up period and these effects were beyond glycemic control. Urinary beta2- and a1-microglobulin are significant biomarkers for incipient diabetic nephropathy and diabetic cerebral microangiopathy. These biomarkers showed that proximal tubule dysfunction may develop before the stage of microalbuminuria.
Petrica
Ligia
L
Department of Nephrology, Victor Babes University of Medicine and Pharmacy, County Emergency Hospital Timisoara, Romania. ligiapetrica@rdslink.ro
Petrica
Maxim
M
Vlad
Adrian
A
Dragos Jianu
Catalin
C
Gluhovschi
Gheorghe
G
Ianculescu
Calina
C
Dumitrascu
Victor
V
Giju
Sorin
S
Gluhovschi
Cristina
C
Bob
Flaviu
F
Ursoniu
Sorin
S
Gadalean
Florica
F
Velciov
Silvia
S
Bozdog
Gheorghe
G
Marian
Roxana
R
D000419:Albuminuria / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C057619:glimepiride