Hypouricemia linked to an overproduction of nitric oxide is an early marker of oxidative stress in female subjects with type 1 diabetes.
OBJECTIVE
The aim of this study is to verify whether, early in the course of type 1 diabetes and assuming hyperglycemia as the only risk factor, women demonstrate a change in oxidative status due to an interaction between nitric oxide (NO) and uric acid production.


METHODS
Thirty-eight women with type 1 diabetes of less than 10 years' duration and with no diabetic complications were compared with 25 matched healthy female controls. Insulin, C-peptide, NO, HbA(1c) and oxidative stress metabolites were determined from venous blood samples taken from all patients after a 12 h overnight fast. Urine samples were used for urinary uric acid determination.


RESULTS
Most oxidative stress metabolites were significantly increased (p < 0.0001), while plasmatic and urinary uric acid levels were significantly lower (p < 0.0001) in patients with type 1 diabetes compared with controls. Mean NO levels were inversely related to uricemia. Bivariate regression analysis showed a significant correlation between plasmatic uric acid and NO (p = 0.004), ascorbic acid (p = 0.042), triglycerides (p = 0.014) and HbA(1c) (p < 0.0001). Linear multivariate regression analysis showed a significant relationship between HbA(1c) and plasmatic uric acid (beta = - 0.465, p = 0.0004).


CONCLUSIONS
Oxidative stress is already present in the early stages of type 1 diabetes. We conclude that the initial increase in oxidative stress could be linked to a reduction in plasmatic levels of uric acid, which is probably directly caused by an overproduction of NO.
Pitocco
Dario
D
Department of Internal Medicine, Catholic University, Rome, Italy. dario.pitocco@rm.unicatt.it
Di Stasio
Enrico
E
Romitelli
Federica
F
Zaccardi
Francesco
F
Tavazzi
Barbara
B
Manto
Andrea
A
Caputo
Salvatore
S
Musella
Tittania
T
Zuppi
Cecilia
C
Santini
Stefano A
SA
Ghirlanda
Giovanni
G
D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D033461:Hyperuricemia / Q000097:blood*; D007328:Insulin / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress; D014527:Uric Acid / Q000097:blood*
D000975:Antioxidants; D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin; D009569:Nitric Oxide; D014527:Uric Acid