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

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

doi:10.1210/jc.2017-01057

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

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

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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.

Original language	English
Pages (from-to)	3600-3609
Number of pages	10
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	102
Issue number	9
Early online date	20 Jul 2017
DOIs	https://doi.org/10.1210/jc.2017-01057
Publication status	Published - 1 Sep 2017

Keywords

Age Factors
Aged
Biomarkers/blood
C-Reactive Protein/metabolism
Cardiovascular Diseases/epidemiology
Cross-Sectional Studies
Diabetes Mellitus, Type 2/epidemiology
Disease Progression
Finland/epidemiology
Glycoproteins/metabolism
Humans
Hypertension/epidemiology
Incidence
Insulin Resistance
Male
Metabolic Syndrome/epidemiology
Middle Aged
Prognosis
Prospective Studies
Risk Assessment
Survival Analysis

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MRC UoB UNITE Unit - Programme 1
Davey Smith, G.
1/06/13 → 31/03/18
Project: Research

Cite this

@article{3bf5566970ed4c4bb9a04f1397e10704,

title = "Differential Associations of Inflammatory Markers With Insulin Sensitivity and Secretion: The Prospective METSIM Study",

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.",

keywords = "Age Factors, Aged, Biomarkers/blood, C-Reactive Protein/metabolism, Cardiovascular Diseases/epidemiology, Cross-Sectional Studies, Diabetes Mellitus, Type 2/epidemiology, Disease Progression, Finland/epidemiology, Glycoproteins/metabolism, Humans, Hypertension/epidemiology, Incidence, Insulin Resistance, Male, Metabolic Syndrome/epidemiology, Middle Aged, Prognosis, Prospective Studies, Risk Assessment, Survival Analysis",

author = "Maria Fizelova and Raimo Jauhiainen and Kangas, {Antti J} and Pasi Soininen and Mika Ala-Korpela and Johanna Kuusisto and Markku Laakso and Alena Stanc{\'a}kov{\'a}",

year = "2017",

month = sep,

day = "1",

doi = "10.1210/jc.2017-01057",

language = "English",

volume = "102",

pages = "3600--3609",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "9",

}

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; Stancáková, Alena.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 102, No. 9, 01.09.2017, p. 3600-3609.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Differential Associations of Inflammatory Markers With Insulin Sensitivity and Secretion

T2 - The Prospective METSIM Study

AU - Fizelova, Maria

AU - Jauhiainen, Raimo

AU - Kangas, Antti J

AU - Soininen, Pasi

AU - Ala-Korpela, Mika

AU - Kuusisto, Johanna

AU - Laakso, Markku

AU - Stancáková, Alena

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

KW - Age Factors

KW - Aged

KW - Biomarkers/blood

KW - C-Reactive Protein/metabolism

KW - Cardiovascular Diseases/epidemiology

KW - Cross-Sectional Studies

KW - Diabetes Mellitus, Type 2/epidemiology

KW - Disease Progression

KW - Finland/epidemiology

KW - Glycoproteins/metabolism

KW - Humans

KW - Hypertension/epidemiology

KW - Incidence

KW - Insulin Resistance

KW - Male

KW - Metabolic Syndrome/epidemiology

KW - Middle Aged

KW - Prognosis

KW - Prospective Studies

KW - Risk Assessment

KW - Survival Analysis

U2 - 10.1210/jc.2017-01057

DO - 10.1210/jc.2017-01057

M3 - Article (Academic Journal)

C2 - 28911155

VL - 102

SP - 3600

EP - 3609

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 9

ER -

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

Abstract

Keywords

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MRC UoB UNITE Unit - Programme 1

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