Association of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes.
OBJECTIVE
We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin, proinflammatory cytokines IL-1 beta, IL-6, and CCL2, and tumor necrosis factor-alpha with beta-cell function, metabolic status, and clinical remission in patients with recent-onset type 1 diabetes.


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 beta-cell function was complemented by the negative association of IL-1 beta 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 beta-cell capacity in type 1 diabetes. This novel finding indicates that administration of IL-1ra, successfully improving beta-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.
Pfleger
Christian
C
Institute for Clinical Diabetes Research at German Diabetes Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany. ch.pfleger@web.de
Mortensen
Henrik B
HB
Hansen
Lars
L
Herder
Christian
C
Roep
Bart O
BO
Hoey
Hillary
H
Aanstoot
Henk-Jan
HJ
Kocova
Mirjana
M
Schloot
Nanette C
NC
D052242:Adiponectin / Q000097:blood*; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007223:Infant; D053577:Interleukin-1 Receptor Accessory Protein / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male
D052242:Adiponectin; D001786:Blood Glucose; D002096:C-Peptide; D016207:Cytokines; D006442:Glycated Hemoglobin; D053577:Interleukin-1 Receptor Accessory Protein; C507765:IL1RAP protein, human