Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes

Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes Christian Pfleger 1 , Henrik B. Mortensen 2 , Lars Hansen 3 , Christian Herder 1 , Bart O. Roep 4 , Hillary Hoey 5 , Henk-Jan Aanstoot 6 , Mirjana Kocova 7 , Nanette C. Schloot 1 8 and on behalf of the Hvidøre Study Group on Childhood Diabetes 1 Institute for Clinical Diabetes Research, German Diabetes Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany 2 Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark 3 Development Projects, Novo Nordisk A/S, Bagsværd, Denmark 4 Department of Immunohaematology and Blood and Transfusion, Leiden University Medical Center, Leiden, the Netherlands 5 University of Dublin, National Children’s Hospital, Tallaght, Ireland 6 Diabetes Center for Pediatric and Adolescent Diabetes Care and Research, Rotterdam, the Netherlands 7 Paediatric Clinic, Department of Endocrinology and Genetics, Skopje, Republic of Macedonia 8 Centre for Internal Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany Address correspondence and reprint requests to Christian Pfleger, Institute for Clinical Diabetes Research at German Diabetes Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail: ch.pfleger{at}web.de Abstract OBJECTIVE— We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin, proinflammatory cytokines IL-1β, IL-6, and CCL2, and tumor necrosis factor-α with β-cell function, metabolic status, and clinical remission in patients with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS— Serum was obtained from 256 newly diagnosed patients (122 males and 134 females, median age 9.6 years). Stimulated C-peptide, blood glucose, and A1C were determined in addition to circulating concentration of cytokines at 1, 6, and 12 months after diagnosis. Analyses were adjusted for sex, age, and BMI percentile. RESULTS— Anti-inflammatory IL-1ra was positively associated with C-peptide after 6 ( P = 0.0009) and 12 ( P = 0.009) months. The beneficial association of IL-1ra on β-cell function was complemented by the negative association of IL-1β with C-peptide after 1 month ( P = 0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after 6 and 12 months ( P < 0.05) and positively correlated with A1C after 1