title: Circulating immune mediators are closely linked in adult-onset type 1 diabetes as well as in non-diabetic subjects.
abstract: Relationships between circulating immune mediators (cytokines, chemokines and growth factors) and a beta cell destructive autoimmune process in adult-onset type 1 diabetes are poorly elucidated. We measured serum levels of immune mediators in type 1 diabetic patients in the context of ongoing deterioration of endogenous insulin secretion. Levels of 27 immune mediators were measured in 34 GADA (glutamic acid decarboxylase antibodies) positive type 1 diabetic patients, aged 27.4 ± 1.2 years at a mean of 7 weeks after diagnosis (designated 0 month) and 6 months later. Endogenous insulin secretion was assessed by C-peptide glucagon stimulation tests during 12 months. Additional data (for baseline analysis) was obtained in 9 GADA positive type 1 diabetic subjects and in 43 non-diabetic age- and sex-matched subjects. In general, the levels of immune mediators displayed large inter- but small intra-individual differences with only minor changes observed between measurements at 0 month and at 6 months. Levels of the majority of immune mediators were strongly and positively correlated to each other not only in the diabetic, but also in the non-diabetic subjects. Body weight (BMI) was positively associated with levels of IL-1 ra, IL-2, IL-4, IL-6, IL-17, Basic FGF, GCSF, IFN gamma and MIP-1 alpha. Adjustment for BMI removed most associations to C-peptide. When adjusted for BMI, levels at 0 month for Basic FGF and MIP-1 alpha were inversely associated with the percentage decline in stimulated C-peptide from 0 to 12 months (nominally p < 0.05). We conclude that associations between different immune mediators are strikingly but not exclusively tied in autoimmune diabetes. BMI is a major confounder in the analysis of associations to autoimmunity. Associations of beta cell decline to individual immune mediators need confirmation in further studies.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim , Norway .
authors.forename: Hanne Fiskvik
authors.initials: HF
authors.lastname: Fleiner
authors.forename: Maria
authors.initials: M
authors.lastname: Radtke
authors.forename: Liv
authors.initials: L
authors.lastname: Ryan
authors.forename: Torolf
authors.initials: T
authors.lastname: Moen
authors.forename: Valdemar
authors.initials: V
authors.lastname: Grill
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015551:Autoimmunity / Q000276:immunology; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000276:immunology; D008297:Male; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D002096:C-Peptide; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D016207:Cytokines; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2
keywords: BMI; C-peptide; chemokines; cytokines; growth factors