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Cited by 567Adipokines, Inflammation, and Metabolic DiseasesDiabetes, Cardiovascular Risks, and LipoproteinsInflammatory Biomarkers in Disease Prognosis

The DOI matches its Crossref record; 34 of the 37 references it cites were found in a registry or an index.

Circulating Interleukin 6 Levels, Blood Pressure, and Insulin Sensitivity in Apparently Healthy Men and Women

Fernandez-Real, José-Manuel, Vayreda, Montserrat, Richart, Cristobal, Gutierrez, Cristina, Broch, Montserrat, Vendrell, Joan, Ricart, Wifredo·2001·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.86.3.7305
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Abstract

There is increasing evidence that systemic inflammation and insulin resistance constitute interrelated events that contribute to atherosclerosis. We studied the effect of the association between circulating interleukin 6 (IL-6) levels, one of the major mediators of inflammation, and C-reactive protein on insulin resistance and blood pressure in 228 healthy volunteers. The plasma IL-6 concentration was significantly and similarly associated with systolic (SBP) and diastolic (DBP) blood pressure, fasting insulin, and the fasting insulin resistance index (FIRI) in all subjects. When smokers were excluded from the analysis, plasma IL-6 levels correlated with percent fat mass (r = 0.19; P = 0.02), absolute fat mass (r = 0.17; P = 0.03), SBP, DBP, fasting insulin levels, and FIRI. The latter associations persisted after controlling for body mass index (r = 0.15 and r = 0.19; P = 0.02 and P = 0.0004 for SBP and DBP, respectively; r = 0.24 and r = 0.19, P = 0.004 and P = 0.03, for fasting insulin and FIRI, respectively). Gender and smoking status significantly influenced the results. Although IL-6 levels were significantly associated with fasting insulin and FIRI in men, these significant correlations were not observed in women. Conversely, although IL-6 levels were significantly associated with SBP and DBP in women, these coefficients were not statistically significant in men. All of these associations were lost among smokers and remained significant in nonsmokers. As IL-6 is the major mediator of the acute phase response by hepatocytes and induces the synthesis of C-reactive protein (CRP), we also controlled for the latter. Serum CRP levels correlated significantly with IL-6 in all the subjects, but mainly in nonsmokers and men. Of note was that this significant relationship was lost among smokers. CRP was associated with fasting insulin (r = 0.28; P < 0.0001) and FIRI (r = 0.25; P < 0.0001), but not with SBP or DBP (P = NS), in all subjects. Unlike IL-6, the associations between CRP and these parameters were similar in men and women and in smokers and nonsmokers. For insulin and FIRI they were stronger in women and in nonsmokers. CPR significantly correlated with the WHR only in men (r = 0.22; P = 0.01). Using multiple linear regression in a stepwise manner to predict circulating IL-6 levels, smoking status (P = 0.0059) and FIRI (P = 0.03), but not fat mass or SBP, independently contributed to 11% of its variance in men. When CRP was introduced into the model, the latter (P < 0.0001) and smoking status (P = 0.02), but not FIRI, fat mass, or SBP, contributed to 33% of the variance in IL-6 levels. In women, only SBP (P = 0.04) contributed to 5% of its variance. When CRP was introduced into the model, again only SBP (P = 0.01) contributed to 10% of the variance in IL-6 levels. In 25 of these subjects, insulin sensitivity was determined using the frequently sampled iv glucose tolerance test with minimal model analysis, and circulating IL-6 levels were strongly associated with the insulin sensitivity index (r = −0.65; P < 0.0001). Again, this relationship was even stronger in men (r =− 0.75; P < 0.001) and was not significant in women (r = −0.26; P = NS). In all of these subjects, only insulin sensitivity (P = 0.0037), not fat mass, contributed to 21% of the variance of IL-6 levels in a multiple linear regression analysis. In summary, circulating IL-6 levels, by inducing either hypertension in women or insulin resistance in men, constitute a significant proatherogenic cytokine. The mechanisms of these associations should be further investigated.

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Metadata

Authors
Fernandez-Real, J.-M., Vayreda, M., Richart, C., Gutierrez, C., Broch, M., Vendrell, J., & Ricart, W.
Affiliations
  • Unitat de Diabetologia, Endocrinologia i Nutricio, University Hospital of Girona Dr. Josep Trueta, 17007 Girona; Unitat d’Endocrinologia, Hospital of Tarragona Joan XXIII, Facultat Medicina, Institut d’Estudis Avançats, Universitat Rovira i Virgili, 43007 Tarragona, Spain
  • Hospital Universitari Joan XXIII de Tarragona (ES)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2001-03-01
Volume
86
Issue
3
Pages
1154-1159
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem.86.3.7305
OpenAlex
W2025429912
Cited by
567
References
37
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 13 · 2022: 26 · 2021: 20 · 2020: 17 · 2019: 12 · 2018: 19 · 2017: 21 · 2016: 17 · 2015: 20 · 2014: 22 · 2013: 31 · 2012: 30
FWCI
24.58
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
Keywords
interleukin-6, C-reactive protein, insulin resistance, blood pressure, systemic inflammation, fat mass, smoking, sex differences, healthy adults, atherosclerosis risk factors, acute phase response, body mass index, hyperinsulinemia, dyslipidemia, dyslipoproteinemia, dyslipidemia risk factors, dyslipidemia severity
MeSH terms
Adult, Blood Pressure, Body Constitution, C-Reactive Protein, Diastole, Fasting, Female, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Sex Characteristics, Smoking, Systole, Interleukin-6, Body Mass Index, Linear Models

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