| Title: | Meta-analysis investigating the role of interleukin-6 mediated inflammation in type 2 diabetes |
| Journal: | EBioMedicine |
| Published: | 21 Oct 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33096487/ |
| DOI: | https://doi.org/10.1016/j.ebiom.2020.103062 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581887 |
Publication 13701
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Abstract
BACKGROUND: Evidence from animal models and observational epidemiology points to a role for chronic inflammation, in which interleukin 6 (IL-6) is a key player, in the pathophysiology of type 2 diabetes (T2D). However, it is unknown whether IL-6 mediated inflammation is implicated in the pathophysiology of T2D.</p>
METHODS: We performed a meta-analysis of 15 prospective studies to investigate associations between IL-6 levels and incident T2D including 5,421 cases and 31,562 non-cases. We also estimated the association of a loss-of-function missense variant (Asp358Ala) in the IL-6 receptor gene (IL6R), previously shown to mimic the effects of IL-6R inhibition, in a large trans-ethnic meta-analysis of six T2D case-control studies including 260,614 cases and 1,350,640 controls.</p>
FINDINGS: In a meta-analysis of 15 prospective studies, higher levels of IL-6 (per log pg/mL) were significantly associated with a higher risk of incident T2D (1·24 95% CI, 1·17, 1·32; P = 1 × 10-12). In a trans-ethnic meta-analysis of 260,614 cases and 1,350,640 controls, the IL6R Asp358Ala missense variant was associated with lower odds of T2D (OR, 0·98; 95% CI, 0·97, 0·99; P = 2 × 10-7). This association was not due to diagnostic misclassification and was consistent across ethnic groups. IL-6 levels mediated up to 5% of the association between higher body mass index and T2D.</p>
INTERPRETATION: Large-scale human prospective and genetic data provide evidence that IL-6 mediated inflammation is implicated in the etiology of T2D but suggest that the impact of this pathway on disease risk in the general population is likely to be small.</p>
FUNDING: The EPICNorfolk study has received funding from the Medical Research Council (MRC) (MR/N003284/1, MC-UU_12015/1 and MC_PC_13048) and Cancer Research UK (C864/A14136). The Fenland Study is funded by the MRC (MC_UU_12015/1 and MC_PC_13046).</p>
16 Keywords
- Adiposity
- Biomarkers
- Blood Glucose
- Body Weights and Measures
- Cytokines
- Diabetes Mellitus, Type 2
- Disease Susceptibility
- Genetic Predisposition to Disease
- Humans
- Inflammation
- Inflammation Mediators
- Interleukin-6
- Odds Ratio
- Receptors, Interleukin-6
- Risk Factors
- Signal Transduction
11 Authors
- Nicholas Bowker
- Rupal L. Shah
- Stephen J. Sharp
- Jian'an Luan
- Isobel D. Stewart
- Eleanor Wheeler
- Manuel A.R. Ferreira
- Aris Baras
- Nicholas J. Wareham
- Claudia Langenberg
- Luca A. Lotta
1 Application
| Application ID | Title |
|---|---|
| 44448 | The genetic and environmental determinants of cardiometabolic and related disorders. |
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