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J Clin Endocrinol Metab. 2015 Sep;100(9):E1179-87. doi: 10.1210/JC.2015-1388. Epub 2015 Jul 9.

Large-Scale Discovery and Validation Studies Demonstrate Significant Reductions in Circulating Levels of IL8, IL-1Ra, MCP-1, and MIP-1β in Patients With Type 1 Diabetes.

Author information

1
Center for Biotechnology and Genomic Medicine (S.P., A.S., D.H., L.S., J-X.S.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; Atlanta Diabetes Associates (B.B.), Atlanta, Georgia 30318; Pediatric Endocrine Associates (S.W.A.), Atlanta, Georgia 30342; Southeastern Endocrine and Diabetes (J.C.R., R.D.S.), Atlanta, Georgia 30076; and Department of Endocrinology (T.Y.), First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 210029.

Abstract

CONTEXT:

Previous studies have attempted to elucidate the potential role of various cytokines and chemokines in human type 1 diabetes (T1D); however, the precise role of these serum proteins in T1D is still controversial and undetermined primarily due to the small sample sizes of the previous studies. We profiled a panel of serum cytokines and chemokines using a large-scale, two-stage study design for the discovery and validation of the serum proteins associated with T1D.

PARTICIPANTS:

The participants were patients with T1D and islet autoantibody-negative control subjects from the Phenome and Genome of Diabetes Autoimmunity study.

MAIN OUTCOME MEASURES:

Thirteen cytokines and chemokines were measured in serum of 4424 subjects using multiplex immunoassays.

RESULTS:

Using 1378 samples in Stage 1, we found that four of the 13 proteins are significantly lower in patients with T1D than controls (IL8: odds ratio [OR] = 0.40; P = 5.7 × 10(-19); IL-1Ra: OR = 0.42; P = 1.1 × 10(-13); MCP-1: OR = 0.60; P = 6.7 × 10(-9); and MIP-1β: OR = 0.63; P = 4.2 × 10(-7)). Our confirmation data with 3046 samples in Stage 2 further confirmed the significant negative associations of these four proteins with T1D (IL8: OR = 0.43; P = 8.9 × 10(-32); IL-1Ra: OR = 0.56, P = 3.7 × 10(-27); MCP-1: OR = 0.61, P = 4.3 × 10(-17); and MIP-1β: OR = 0.69, P = 2.4 × 10(-13)). Quartile analyses also suggested that significantly more T1D cases have protein levels in the bottom quartile than in the top quartile for all four proteins: IL8 (OR = 0.09), IL-1Ra (OR = 0.18), MCP-1 (OR = 0.38), and MIP-1β (OR = 0.44). Furthermore, the negative associations between T1D and serum levels of all four proteins are stronger in genetically high-risk groups compared with the moderate and low-risk groups.

CONCLUSIONS:

IL8, IL-1Ra, MCP-1, and MIP-1β are significantly lower in patients with T1D than controls.

PMID:
26158606
PMCID:
PMC4570171
DOI:
10.1210/JC.2015-1388
[Indexed for MEDLINE]
Free PMC Article

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