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the study group consisted of 186 caucasian nondiabetic subjects participating in the catanzaro metabolic risk factors study ( catameris ) , a metabolic disease prevention campaign for cardiometabolic risk factors ( 6 ) .
after 12-h fasting , subjects underwent an oral glucose tolerance test and a euglycemic - hyperinsulinemic clamp , as previously described ( 6 ) .
whole - body glucose disposal ( wbgd ) was calculated as reported ( 6 ) .
mets was defined according to american heart association and national heart , lung , and blood institute criteria .
the study was approved by the institutional ethics committees , and written consent was obtained from all participants . variables with skewed distribution were log transformed for analyses .
a logistic regression analysis was used to determine the association between the tertiles of igf-1 or il-6 and the mets and its individual components .
relationships between variables were sought by multivariate linear regression analysis to assess the magnitude of their effect on wbgd .
after adjusting for sex and age , igf-1 levels were negatively correlated with bmi , waist circumference , systolic blood pressure , triglycerides , fasting insulin , and homa and positively correlated with wbgd . after adjusting for age and sex , il-6 levels
were positively correlated with bmi , waist circumference , systolic blood pressure , fasting insulin , and homa and negatively correlated with wbgd and igf-1 levels . in a logistic regression model adjusted for age and sex , igf-1 in the lowest tertile ( < 135 ng / ml ) was associated with an increased risk of having mets ( odds ratio [ or ] 3.07 [ 95% ci 1.27.9 ] ) , low hdl choldesterol ( 3.15 , [ 1.28.1 ] ) , and larger waist circumference ( 4.67 , [ 1.811.9 ] ) compared with the highest tertile ( > 221 ng / ml ) . after adjusting for age , sex , and lipid levels , igf-1 in the lowest tertile was associated with increased risk of insulin resistance , i.e. , the highest homa tertile ( 3.08 , [ 1.27.6 ] ) or lowest wbgd tertile ( 3.31 , [ 1.0110.9 ] ) .
conversely , in a logistic regression model adjusted for age and sex , il-6 in the highest tertile ( > 2.5 pg / ml ) was associated with an increased risk of having mets ( 3.21 [ 1.28.1 ] ) , high blood pressure ( 2.63 [ 1.16.4 ] ) , and larger waist circumference ( 4.42 [ 1.811.0 ] ) compared with the lowest tertile ( < 1.3 pg / ml ) . after adjusting for age , sex , and lipid levels , il-6 in the highest tertile
was associated with increased risk of insulin resistance , i.e. , the highest homa tertile ( 2.14 , [ 1.015.31 ] ) or lowest wbgd tertile ( 4.64 , [ 1.514.1 ] ) . to estimate the independent contribution of variables to wbgd
, we carried out a multivariate regression analysis in a model including age , sex , bmi , waist circumference , triglycerides , hdl cholesterol , il-6 , igf-1 , and fasting and 2-h postchallenge glucose levels .
the four variables that remained significantly associated with wbgd were age ( p = 0.01 ) , waist circumference ( p = 0.01 ) , 2-h postchallenge glucose ( p = 0.001 ) , and il-6 ( p = 0.04 ) , accounting for 61.2% of its variation .
in this study , we report an inverse relationship between plasma igf-1 and il-6 levels consistent with clinical ( 7 ) and experimental data showing that igf-1 acts as an anti - inflammatory molecule inhibiting il-6 expression ( 4 ) and that il-6 decreases igf - i levels by increasing its clearance ( 5 ) .
both igf-1 and il-6 are associated with mets and its individual components , but in opposite directions .
higher il-6 and lower igf-1 levels confer increased risk of having mets and its two underlying pathophysiological abnormalities , i.e. , visceral obesity and insulin resistance .
interestingly , multivariate regression analysis showed that il-6 but not igf-1 levels were independently associated with wbgd .
these results raise the possibility that proinflammatory molecules may have a more important role than anti - inflammatory proteins in the development of insulin resistance and mets .
this study has some limitations : first , its cross - sectional nature makes it impossible to draw any conclusions on causality .
furthermore , while increasing evidence supports the concept that a low - grade proinflammatory state associated with increased visceral adiposity may induce insulin resistance and hence mets ( 1 ) , it has been recently demonstrated ( 8) that acute il-6 exposure directly increases glucose metabolism in intact human skeletal muscle ; our data do not allow exclusion of the possibility that increased il-6 levels in our population may represent an attempt to counteract insulin resistance by increasing glucose transport .
however , it has also been observed ( 9 ) that reduced igf-1 levels are protective and associated with prolonged lifespan in centenarians , and we can not exclude that in the study population decreased igf-1 levels represent a reactive rather than a causative state .
objective  to examine the relationship between plasma igf-1 and interleukin-6 ( il-6 ) levels in caucasian nondiabetic subjects and evaluate the association of igf-1 and il-6 with the cardiometabolic risk factors characterizing metabolic syndrome ( mets).research design and methods  the study group consisted of 186 caucasian nondiabetic subjects who underwent an oral glucose tolerance test and an euglycemic - hyperinsulinemic clamp . a logistic regression analysis , adjusted for age and sex , was used to determine the association between tertiles of igf-1 and il-6 and the mets and its components.resultsafter adjusting for age and sex , both igf-1 and il-6 were correlated with insulin resistance and individual components of mets , but in opposite directions . in the logistic regression model adjusted for age and sex , higher il-6 and lower igf-1 levels confer increased risk of having mets and its two underlying pathophysiological abnormalities , i.e. , visceral obesity and insulin resistance.conclusionsthe present results raise the possibility that lowered protection against inflammation , i.e. , lower igf-1 levels , may have a role in the development of mets and its features , resulting in an imbalance between proinflammatory and anti - inflammatory proteins .