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Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

Herder, C; Faerch, K; Carstensen-Kirberg, M; Lowe, GD; Haapakoski, R; Witte, DR; Brunner, EJ; ... Vistisen, D; + view all (2016) Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study. European Journal of Endocrinology , 175 (5) pp. 367-377. 10.1530/EJE-16-0528. Green open access

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Abstract

Objective: Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional. Design and methods: We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers. Results: Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin. Conclusions: Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammation-related processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function.

Type: Article
Title: Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1530/EJE-16-0528
Publisher version: http://dx.doi.org/10.1530/EJE-16-0528
Language: English
Additional information: Disclaimer: this is not the definitive version of record of this article.This manuscript has been accepted for publication in European Journal of Endocrinology, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at http://dx.doi.org/10.1530/EJE-16-0528 2016.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: https://discovery-pp.ucl.ac.uk/id/eprint/1508981
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