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Association of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes

¹Institute for Clinical Diabetes Research, German Diabetes Centre, Leibniz Institute at Heinrich-Heine-University Duesseldorf, Germany
²Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark
³Centre for Internal Medicine, Heinrich- Heine-University Düsseldorf, Germany
⁴Preclinical development, Novo Nordisk A/S, Bagsværd, Denmark
⁵Department of Immunohaematology and Blood and Transfusion, Leiden University, Medical Center, Leiden, The Netherlands
⁶University of Dublin, National Children's Hospital, Tallaght, Ireland
⁷Diabetes Center for Pediatric and Adolescent Diabetes Care and Research, Rotterdam, The Netherlands
⁸Paediatric Clinic, Department of Endocrinology and Genetics, Skopje, Republic of Macedonia

Objective: We investigated the association of anti-inflammatory cytokines interleukin-1 receptor antagonist (IL-1ra) and adiponectin as well as pro-inflammatory cytokines IL-1β, IL-6, CCL2 and tumor necrosis factor (TNF)- 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/134 females, median age 9.6 years). Stimulated C-peptide, blood glucose and HbA1c were determined in addition to circulating concentration of cytokines at one, six and twelve months after diagnosis. Analyses were adjusted for sex, age and BMI percentiles.

Results: Anti-inflammatory IL-1ra was positively associated with C-peptide after six (p=0.0009) and twelve months (p=0.009). The beneficial association of IL-1ra on β-cell function was complemented by the negative association of IL-1β with C-peptide after one month (p=0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after six and twelve months (p<0.05) and positively correlated to HbA1c after one month (p=0.0004). Proinflammatory IL-6 was elevated in patients with good metabolic control after one month (p=0.009) and showed a positive association with blood glucose disposal after twelve 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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