Differential associations of inflammatory markers with insulin sensitivity and secretion : the prospective METSIM study
Fizelova, Maria; Jauhiainen, Raimo; Kangas, Antti J.; Soininen, Pasi; Ala-Korpela, Mika; Kuusisto, Johanna; Laakso, Markku; Stančáková, Alena (2017-07-20)
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, https://doi.org/10.1210/jc.2017-01057
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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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