Differential Associations of Inflammatory Markers With Insulin Sensitivity and Secretion: The Prospective METSIM Study.

Alena Stančáková,Maria Fizelova,Mika Ala-Korpela,Raimo Jauhiainen,Markku Laakso,Pasi Soininen,Johanna Kuusisto,Antti J Kangas

doi:10.1210/jc.2017-01057

Abstract

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.

Highlights

MethodsSubjects The Metabolic Syndrome in Men (METSIM) study included 10,197 Finnish middle-aged men randomly selected from the population register of Kuopio, Eastern Finland (population, 105,000)
Context: Low-grade inflammation is involved in the development of type 2 diabetes and cardiovascular disease (CVD); prospective studies evaluating inflammatory markers as predictors of changes in insulin secretion and insulin sensitivity are lacking
We investigated the associations of glycoprotein acetyls (GlycA), interleukin-1 receptor antagonist (IL-1RA), and high-sensitivity C-reactive protein with insulin secretion, insulin sensitivity, incident type 2 diabetes, hypertension, CVD events, and total mortality in the prospective Metabolic Syndrome in Men (METSIM) study

Summary

Methods

Subjects The Metabolic Syndrome in Men (METSIM) study included 10,197 Finnish middle-aged men randomly selected from the population register of Kuopio, Eastern Finland (population, 105,000). The baseline study was performed from 2005 to 2010 at the Clinical Research Unit, University of Eastern Finland, Kuopio, Finland. The present study included 8749 men without type 2 diabetes at baseline [mean age, 57.2 6 7.1 years; body mass index (BMI), 26.8 6 3.8 kg/m2]. The ethics committees of the University of Eastern Finland and Kuopio University Hospital approved the present study, which was conducted in accordance with the Declaration of Helsinki. Two datasets of the METSIM study were used in the prospective analyses

Results

Discussion

Conclusion