{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T07:15:23Z","timestamp":1789888523725,"version":"4.0.1"},"reference-count":0,"publisher":"American Diabetes Association","issue":"7","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,7,1]]},"abstract":"<jats:p>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 &amp;lt; 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 &amp;lt; 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.<\/jats:p>","DOI":"10.2337\/diabetes.49.7.1258","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1258-1263","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":113,"title":["Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: relation to glomerular hyperfiltration."],"prefix":"10.2337","volume":"49","author":[{"given":"F","family":"Chiarelli","sequence":"first","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Cipollone","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Romano","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Tumini","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Costantini","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"di Ricco","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Pomilio","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S D","family":"Pierdomenico","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Marini","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Cuccurullo","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Mezzetti","sequence":"additional","affiliation":[{"name":"Centro per lo Studio dell'Ipertensione Arteriosa delle Dislipidemie e dell'Aterosclerosi, Department of Biomedical Sciences, University G.D'Annunzio School of Medicine, Chieti, 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