Asymmetric dimethylarginine in young people with Type 1 diabetes: a paradoxical association with HbA1c

P>Aims Asymmetric dimethylarginine (ADMA) is an independent risk factor for cardiovascular disease and its concentrations are increased in several diseases, including diabetes. However, there is limited information on this plasma marker in young people, particularly in those with Type 1 diabetes. The aim of the present study was therefore to perform a longitudinal evaluation of plasma ADMA and of its determinants in young people with childhood-onset Type 1 diabetes. Methods For measurement of ADMA using mass spectrometry, 1018 longitudinal stored blood samples were available from 330 young people with Type 1 diabetes followed in the Oxford Regional Prospective Study. Additional data concerning annual assessments of HbA(1c), height, weight, insulin dose and three early morning urine samples for measurement of the albumin/creatinine ratio were available. Results ADMA levels were significantly higher in males than in females (mean +/- sd: 0.477 +/- 0.090 vs. 0.460 +/- 0.089 mu mol/l, P = 0.002) and declined with chronological age (estimate +/- se: -0.0106 +/- 0.0008, P < 0.001). A significant inverse association was detected between ADMA and HbA(1c) (estimate +/- se: -0.0113 +/- 0.001, P < 0.001). ADMA levels were lower in subjects developing microalbuminuria (mean +/- sd: 0.455 +/- 0.093 vs. 0.476 +/- 0.087 mu mol/l, P = 0.001) than in subjects with normoalbuminuria, but this difference disappeared after adjusting for HbA(1c). Conclusions In this longitudinal study, ADMA concentrations decreased with age and were significantly higher in males and lower in subjects developing microalbuminuria. These associations were largely explained by a paradoxical negative association between HbA(1c) and ADMA. We suggest that chronic hyperglycaemia might down-regulate mechanisms implicated in ADMA production or stimulate its metabolism confounding short-term associations with complications risk.