Serum and urinary nitric oxide in Type 2 diabetes with or without microalbuminuria: relation to glomerular hyperfiltration.
BACKGROUND
Glomerular hyperfiltration is considered as one of the pathophysiological mechanisms for the development of diabetic nephropathy. Oxidative stress is enhanced in patients with diabetes mellitus. Reportedly, nitric oxide (NO) might be involved in the pathogenesis of hyperfiltration. We investigated the relationship between hyperfiltration and NO system, and malondialdehyde (MDA) levels in Type 2 diabetics with/without microalbuminuria.


METHODS
In 39 microalbuminuric, 29 normoalbuminuric Type 2 diabetic patients and 32 healthy controls, serum creatinine, nitrite, nitrate, urinary microalbumin, nitrite, nitrate, plasma MDA and estimated glomerular filtration rate (EGFR) values, calculated according to the Cockcroft and Gault formula, were recorded.


RESULTS
Serum and urine NO levels were higher in both microalbuminurics and normoalbuminurics than controls. There were no significant differences in EGFR between groups. However, hyperfiltration was determined in 31% of normoalbuminurics and 20% of microalbuminurics. Serum and urine NO levels were higher in patients with hyperfiltration. Plasma MDA levels were significantly elevated in both microalbuminurics and normoalbuminurics when compared with controls. Serum glucose and microalbuminuria were positively correlated in microalbuminuric diabetics. Serum NO levels were also positively correlated with EGFR in both normoalbuminurics and microalbuminurics. HbA1c levels were positively correlated with both urinary albumin excretion and plasma MDA levels in normoalbuminuric diabetics.


CONCLUSIONS
Hyperglycemia is associated with an increased NO biosynthesis and lipid peroxidation. Increased oxidative stress may contribute to the high NO levels in Type 2 diabetes. Furthermore, the high NO levels may lead to hyperfiltration and hyperperfusion, which in turn leads to an increase in urinary albumin excretion and thus causes progression of nephropathy in early Type 2 diabetes.
Department of Clinical Biochemistry, Ege University Faculty of Medicine, Bornova, 35100, Izmir, Turkey.
Saliha
S
Apakkan Aksun
Bilgin
B
Ozmen
Dilek
D
Ozmen
Zuhal
Z
Parildar
Belgin
B
Senol
Sara
S
Habif
Işil
I
Mutaf
Nevbahar
N
Turgan
Oya
O
Bayindir
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000150:complications / Q000503:physiopathology* / Q000652:urine; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000652:urine*; D003928:Diabetic Nephropathies / Q000209:etiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism* / Q000652:urine; D009573:Nitrites / Q000097:blood / Q000652:urine; D012016:Reference Values
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008315:Malondialdehyde; D009566:Nitrates; D009569:Nitric Oxide; D009573:Nitrites