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

Abbreviations: IL, interleukin; TNF, tumor necrosis factor

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- 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 month (P = 0.0004). Proinflammatory IL-6 was elevated in patients with good metabolic control after 1 month (P = 0.009) and showed a positive association with blood glucose disposal after 12 months (P = 0.047).

CONCLUSIONS—IL-1ra is associated with preserved β-cell capacity in type 1 diabetes. This novel finding indicates that administration of IL-1ra, successfully improving β-cell function in type 2 diabetes, may also be a new therapeutic approach in type 1 diabetes. The relation of adiponectin and IL-6 with remission and metabolic status transfers observations from in vitro and animal models into the human situation in vivo.

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