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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adult, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glomerular Filtration Rate, Glycated Hemoglobin A, Glycemic Index, Humans, Kidney, Male, Middle Aged, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type III, Renal Circulation.
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Is poor glycemic control related to increased nitric oxide activity within the renal circulation of patients with type 2 diabetes? Context: Experimental studies have shown that glucose releases endothelial nitric oxide (NO) and that NO contributes to renal hyperperfusion in models of diabetes. To examine whether this translates into the human condition, we studied the relationship between glycemic control and renal NO activity in patients with type 2 diabetes. A total of 113 patients with type 2 diabetes and a wide range of HbA1c concentrations were included. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were determined by constant infusion input clearance. Functional NO activity in the renal circulation was determined as change of RPF to infusion of the NO synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (4.25 mg/kg). As additional markers, we measured urinary excretion of NO (UNOx) and L-arginine-to-asymmetrical dimethylarginine (ADMA) ratio in plasma. Subjects within the highest tertile of HbA1c concentration had increased RPF (low, medium, and high tertiles 576 ± 17 vs. 585 ± 22 vs. 627 ± 33 mL/min/m(2), P = 0.05 by one-way ANOVA), while GFR was similar across tertiles. The response of RPF to NOS blockade was augmented in subjects with higher HbA1c levels (-55 ± 7 vs. -64 ± 8 vs. -86 ± 8 mL/min, P = 0.04 by one-way ANOVA). Further, L-arginine-to-ADMA ratio and UNOx were increased in subjects with higher HbA1c levels.
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In line with experimental evidence, we could demonstrate in humans that poor glycemic control is related to higher NO activity and hyperperfusion of the kidney. The renal NO system may thus be a novel therapeutic target for improving renal hemodynamics in patients with diabetes. Final Decision: yes