Circulating Interleukin 6 Levels, Blood Pressure, and Insulin Sensitivity in Apparently Healthy Men and Women
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 prote...
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Published in | The journal of clinical endocrinology and metabolism Vol. 86; no. 3; pp. 1154 - 1159 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
Endocrine Society
01.03.2001
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Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.86.3.7305 |