Pediatric Diabetes 2016 doi: 10.1111/pedi.12384 All rights reserved © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Pediatric Diabetes Original Article Osteoprotegerin, RANKL, ADMA, and Fetuin-A serum levels in children with type I diabetes mellitus Chrysis D, Efthymiadou A, Mermigka A, Kritikou D, Spiliotis BE. Osteoprotegerin, RANKL, ADMA, and Fetuin-A serum levels in children with type I diabetes mellitus. Pediatric Diabetes 2016. Introduction: Patients with type I diabetes mellitus (T1DM) have increased incidence of atherosclerosis and cardiovascular disease. Although these complications are unusual in children with T1DM, prevention, and early intervention could decrease morbidity and mortality. Osteoprotegerin (OPG), asymmetric dimethylarginine (ADMA), and Fetuin-A have been associated with increased cardiovascular risk (CVR). Increased OPG and ADMA, and decreased or increased Fetuin-A serum levels have been associated with increased CVR. Aim: Because patients with T1DM have higher CVR we investigated OPG, ADMA, and Fetuin-A, in children with T1DM. Methods: We determined the serum levels of OPG, receptor activator of nuclear factor-κB ligand (RANKL), ADMA, and Fetuin-A by enzyme-linked immunosorbent assay (ELISA) in 56 children with T1DM aged 12.1 ± 3.4 yr and in 46 normal control children, (C) aged 11.3 ± 3.0 yr. Results: Serum OPG levels were significantly increased in patients with T1DM (3.352 ± 0.73 pmol/L) compared with C (2.75 ± 0.67 pmol/L, p < 0.0001) but RANKL did not change. ADMA was significantly decreased in T1DM compared with C (0.68 ± 0.13 μmol/L versus 0.82 ± 0.18 μmol/L, p < 0.0001). Fetuin-A was similar in T1DM (0.551 ± 0.13 g/L) and C (0.540 ± 0.11 g/L) subjects. OPG was positively associated with glycosylated hemoglobin A1c (p < 0.001) and negatively associated with BMI (p < 0.01). ADMA and Fetuin-A were not associated with A1c and ADMA was only negatively associated with age (p < 0.05). Conclusion: OPG is increased, ADMA is decreased, but RANKL and Fetuin-A are unchanged in T1DM children. Whereas increased OPG has been firmly related to increased CVR, more studies, especially longitudinal studies, are needed to delineate the role and clinical significance of decreased ADMA and if Fetuin-A has any role in T1DM. Dionisios Chrysis a , Alexandra Efthymiadou a , Alexandra Mermigka b , Dimitra Kritikou b and Bessie E Spiliotis a a Division of Endocrinology, Department of Pediatrics, Medical School, University of Patras, Patra, Greece; and b Department of Pediatrics, Medical School, University of Patras, Patra, Greece Key words: osteoprotegerin – ADMA – Fetuin-A – diabetes mellitus type 1 – children Corresponding author: Dionisios Chrysis, MD, PhD, Department of Pediatrics, Division of Endocrinology, Medical School, University of Patras, Rion 26504, Patra, Greece. Tel: (30)2610999546; fax: (30)2610994711; e-mail: dchrysis@upatras.gr Submitted 20 December 2015. Accepted for publication 29 February 2016 Patients with type I diabetes mellitus (T1DM) have a higher incidence of atherosclerosis which appears earlier, and is more severe than in the general popula- tion despite the short duration of the disease, intensive insulin treatment, and lack of microvascular compli- cations (1–3). In addition, these patients have higher morbidity and mortality for premature cardiovascular disease compared with the general population (2, 4 – 6). The mortality in T1DM patients from cardiovascular disease is increased 2 to 20-fold (2, 5, 6) and therefore early identification of T1DM patients with higher cardiovascular risk (CVR) is very important as is early intervention. In children with T1DM, atherosclerosis appears earlier (4) and it is more severe compared with their peers (2), and the mortality from cardiovascular disease has a 12-fold increase in young men with 1