Abstract 4685: High Prevalence of Abnormal Glucose Metabolism and its Relation to Elevated Asymmetric Dimethylarginine in Young Adult Fontan Patients
Background: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide and associates with various pathophysiologies of cardiovascular and metabolic disorders, including impaired glucose tolerance (IGT), which has negative impact on long-term cardiovascular events. No data on its influence on Fontan patients (F), sharing certain characteristics with heart failure, are available.
Purpose: To evaluate glucose metabolic status and its relation to ADMA in Fontan patients.
Method and Results: An oral glucose tolerance test (75gOGTT) was performed in 61 Fontan patients (21± 6 years) and 27 controls (27 ± 6 years) to assess impaired glucose tolerance (IGT) and calculate an area under the curve of plasma glucose (BS-AUC). Plasma ADMA(μmol/l), liver enzyme (r-GTP), and levels of norepinephrine, renin activity, and brain natriuretic peptide were measured. Fontan patients exhibited a higher prevalence of IGT than controls (48% vs, 4%, p < 0.0001) and higher levels of ADMA (0.55±0.10 vs. 0.43±0.07, p < 0.0001) and BS-AUC (p < 0.001). In Fontan patients, greater BS-AUC was associated with male gender, higher levels of ADMA, norepinephrine, renin, and r-GTP. On multivariate analysis, higher ADMA and r-GTP in addition to male gender were independent determinants of high BS-AUC. In contrast, there were no relationships between these variables and the BS-AUC in controls.
Conclusions: Fontan patients have a high prevalence of IGT with a close association with elevated ADMA, implying that, in addition to liver dysfunction, impaired degradation of ADMA by postprandial hyperglycemia is, in part, responsible for the high prevalence of IGT.