Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: relation to glomerular hyperfiltration.
Hyperglycemia has been causally linked to vascular and glomerular dysfunction by a variety of biochemical mechanisms, including a glucose-dependent abnormality in nitric oxide (NO) production and action. NO is a candidate for mediating hyperfiltration and the increased vascular permeability induced by diabetes. Serum nitrite and nitrate (NO2-+ NO3-) concentrations were assessed as an index of NO production in 30 adolescents and young adults with type 1 diabetes, 15 with and 15 without microalbuminuria (albumin excretion rate [AER] between 20 and 200 microg/min), compared with a well-balanced group of healthy control subjects. In all subjects, glomerular filtration rate (GFR) was determined by radionuclide imaging. Our study showed that NO2- + NO3- serum content and GFR values were significantly higher in microalbuminuric diabetic patients than in the other 2 groups. GFR was significantly and positively related to AER levels (r2 = 0.75, P < 0.0001), whereas NO2- + NO3- serum content was independently associated with both AER and GFR values (beta = 2.086, P = 0.05, beta = 1.273, P = 0.0085, respectively), suggesting a strong link between circulating NO, glomerular hyperfiltration, and microalbuminuria in young type 1 diabetic patients with early nephropathy. Interestingly, mean HbA1c, serum concentration was significantly higher in microalbuminuric than in normoalbuminuric diabetic subjects (P < 0.05) and was independently associated with AER values, suggesting a role for chronic hyperglycemia in the genesis of diabetic nephropathy. Moreover, HbA1c serum concentration was significantly and positively related to NO2 + NO3 serum content (r2 = 0.45, P = 0.0063) and GFR values (r2 = 0.57, P = 0.0011), suggesting that chronic hyperglycemia may act through a mechanism that involves increased NO generation and/or action. In conclusion, we suggest that in young type 1 diabetic patients with early nephropathy, chronic hyperglycemia is associated with an increased NO biosynthesis and action that contributes to generating glomerular hyperfiltration and persistent microalbuminuria.
Centro per lo Studio dell'Ipertensione Arteriosa delle Dislipidemie e dell'Aterosclerosi, Department of Biomedical Sciences, University G.D'Annunzio School of Medicine, Chieti, Italy.
F
F
Chiarelli
F
F
Cipollone
F
F
Romano
S
S
Tumini
F
F
Costantini
L
L
di Ricco
M
M
Pomilio
S D
SD
Pierdomenico
M
M
Marini
F
F
Cuccurullo
A
A
Mezzetti
D000293:Adolescent; D000328:Adult; D000419:Albuminuria; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D012016:Reference Values; D012044:Regression Analysis
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D009566:Nitrates; D009569:Nitric Oxide