you come right down to it and that is addressable through various natural interventions.
http://www.google.com/url?sa=t&source=web&cd=2&ved=0CB0QFjAB&url=http%3A%2F%2Fjcem.endojournals.org%2Fcgi%2Freprint%2F92%2F12%2F4569.pdf&rct=j&q=low%20grade%20inflammation%20obesity&ei=OKWSTKu4O4K8lQew2fCnCg&usg=AFQjCNHsGNZpLAER77VTTEjL1vOGgEgdugResults: In age-, sex-, and lipid-adjusted analyses, IL-6, IL-18, IP-10,
and adiponectin (inversely) were associated with both BMI and WC
(all P Յ 0.002). None of the immune markers was related to glucose,
but IL-6, IL-18, and adiponectin (inversely) were associated with
insulin and homeostasis model assessment of insulin resistance in
age- and sex-adjusted models. Adjustment for BMI or WC indicated
that a considerable proportion of these associations may be mediated
by obesity.
Conclusions: We found that a differential low-grade immune acti-
vation is associated with parameters of obesity in adolescents. More-
over, there is evidence that IL-6, IL-18, IP-10, and adiponectin (in-
versely) are associated with insulin resistance and that these
associations can mainly be attributed to obesity. (J Clin Endocrinol
Metab 92: 4569 – 4574, 2007)
IN ADULTS, NUMEROUS STUDIES have shown that a dif-
ferential, subclinical, chronic activation of the immune sys-
tem precedes the manifestation of type 2 diabetes mellitus
(T2DM). Elevated systemic concentrations of specific acute-
phase proteins, cytokines, and chemokines as well as reduced
levels of the adipokine adiponectin predict the development of
T2DM (1, 2).
This association between low-grade inflammation
and T2DM remains significant after adjustment for traditional
risk factors so that it is reasonable to assume that low-grade
inflammation is relevant in the pathogenesis of T2DM. How-
ever, some of the association between elevated levels of im-
mune mediators and T2DM is also explained by obesity be-
cause adipose tissue has been shown to secrete many of the
cytokines and chemokines that are considered T2DM risk fac-
tors (3–7).
The analysis of the role of low-grade inflammation in the
development of insulin resistance and T2DM in children and
adolescents is relevant because, in contrast to adults, it can be
assumed that associations between low-grade inflammation,
insulin resistance, and T2DM are not confounded by chronic
inflammatory conditions such as cardiovascular disease, arthri-
tis, or bronchitis that are frequent comorbidities in T2DM pa-
tients or in old age.
However, to the best of our knowledge, data
from prospective studies that investigate low-grade inflamma-
tion as a risk factor for T2DM in youth are not available. There
is some evidence from case-control and cross-sectional surveys
that low-grade inflammation is associated with T2DM risk and
insulin resistance in children and adolescents. Most data come
from studies that describe the positive association between C-
reactive protein (CRP) and obesity as a major risk factor for
T2DM (8 –21).
Only a few studies also investigated the relationship between CRP and glucose metabolism and found that
higher levels of CRP were associated with elevated fasting
insulin levels and/or insulin resistance (14, 19, 20). These ob-
servations were extended in one study that showed that the
positive association between CRP and insulin is markedly at-
tenuated after adjusting for BMI (14). This finding indicates that
in youth as well as adults, the association between inflamma-
tion and T2DM risk cannot be explained by obesity alone and
may support the development of T2DM at all ages.
Although CRP is widely considered a general marker of
immune activation, cross-sectional studies show that CRP is
only moderately or weakly correlated with many cytokines,
chemokines, and adiponectin (22–24) and that the significant
association between elevated levels of these mediators of innate
immunity and incident T2DM is independent of CRP levels (25,
26).
Thus, it can be expected that these markers represent dif-
ferent components of the immune system and that they provide
different information than CRP measurement. It is therefore
interesting that several other reports suggested that also circu-
lating concentrations of IL-6 (18, 21, 27), TNF␣ (16, 28), soluble
TNF␣ receptors (18, 28, 29), and E-selectin (21) are elevated in
obesity and that IL-6 (27) and soluble TNF␣ receptor 2 may be
associated with insulin resistance in children and adolescents
(29).
In addition, there are data from multiple adolescent popu-
lations on the inverse association between adiponectin and
obesity and insulin resistance (30 –32). Adiponectin may be
largely independent of systemic levels of many cytokines and
chemokines (23) but has been shown to have strong antiin-
flammatory effects on the molecular and cellular level (33, 34)
so that it may also be considered as immune marker.