University of Oulu

Maria Fizelova, Raimo Jauhiainen, Antti J Kangas, Pasi Soininen, Mika Ala-Korpela, Johanna Kuusisto, Markku Laakso, Alena Stančáková; Differential Associations of Inflammatory Markers With Insulin Sensitivity and Secretion: The Prospective METSIM Study, The Journal of Clinical Endocrinology & Metabolism, Volume 102, Issue 9, 1 September 2017, Pages 3600–3609,

Differential associations of inflammatory markers with insulin sensitivity and secretion : the prospective METSIM study

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Author: Fizelova, Maria1; Jauhiainen, Raimo1; Kangas, Antti J.2;
Organizations: 1Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland
2Computational Medicine, Faculty of Medicine, Biocenter Oulu, University of Oulu
3Nuclear Magnetic Resonance Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland
4School of Social and Community Medicine, and Medical Research Council Integrative Epidemiology Unit, University of Bristol
5Department of Medicine, Kuopio University Hospital
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.2 MB)
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Language: English
Published: Endocrine society, 2017
Publish Date: 2017-10-13


Context: Low-grade inflammation is involved in the development of type 2 diabetes and cardiovascular disease (CVD); however, prospective studies evaluating inflammatory markers as predictors of changes in insulin secretion and insulin sensitivity are lacking.

Objective: We investigated the associations of glycoprotein acetyls (GlycA), interleukin-1 receptor antagonist (IL-1RA), and high-sensitivity C-reactive protein (hs-CRP) with insulin secretion, insulin sensitivity, incident type 2 diabetes, hypertension, CVD events, and total mortality in the prospective Metabolic Syndrome in Men (METSIM) study.

Design: A prospective study.

Participants: The cross-sectional METSIM study included 8749 nondiabetic Finnish men aged 45 to 73 years, who had been randomly selected from the population register of Kuopio, Finland. A total of 5401 men participated in the 6.8-year follow-up study.

Main Outcome Measures: Changes in insulin secretion, insulin sensitivity, and cardiometabolic traits during the follow-up period and the incidence of type 2 diabetes, hypertension, CVD events, and total mortality.

Results: During the follow-up period, GlycA was associated with impaired insulin secretion, hyperglycemia, incident type 2 diabetes (hazard ratio, 1.37; 95% confidence interval, 1.29 to 1.46) and CVD (hazard ratio, 1.21; 95% confidence interval, 1.12 to 1.32). IL-1RA and hs-CRP were associated with adverse changes in insulin sensitivity and obesity-related traits and with total mortality (hazard ratio, 1.13; 95% confidence interval, 1.07 to 1.20; and hazard ratio, 1.08; 95% confidence interval, 1.04 to 1.11, respectively).

Conclusions: Inflammatory markers differentially predicted changes in insulin secretion and insulin sensitivity. GlycA predicted impaired insulin secretion, and IL-1RA and hs-CRP predicted changes in insulin sensitivity. Combining the three markers improved the prediction of disease outcomes, suggesting that they capture different aspects of low-grade inflammation.

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Series: Journal of clinical endocrinology & metabolism
ISSN: 0021-972X
ISSN-E: 1945-7197
ISSN-L: 0021-972X
Volume: 102
Issue: 9
Pages: 3600 - 3609
DOI: 10.1210/jc.2017-01057
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by grants from the Academy of Finland, the Finnish Diabetes Research Foundation, and the Finnish Cardiovascular Research Foundation; by Strategic Research Funding from the University of Eastern Finland (Kuopio, Finland) and VTR and EVO grants from the Kuopio University Hospital (to M.L.); and by grants from the Sigrid Juselius Foundation (to M.A.-K.). M.A.-K. works in a unit supported by the University of Bristol and UK Medical Research Council (Grant MC_UU_12013/1). These funding bodies had no role in the design or conduct of the study, collection management, analysis or interpretation of the data, preparation review, or approval of the report.
Copyright information: This article has been published under the terms of the Creative Commons Attribution License (CC BY;, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).