Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance.
BACKGROUND
Adipose tissue-derived adipokines may contribute to insulin resistance.


OBJECTIVE
We tested the hypothesis that adipokines are associated with insulin resistance in a community-based cohort and that associations are maintained in people with and without the metabolic syndrome (high vs. low risk of diabetes).


METHODS
We studied a cross-sectional sample of 2356 individuals attending the seventh examination (1998-2001) of the Framingham Offspring Study. We measured levels of glucose, insulin, adiponectin, resistin, and TNFalpha in fasting blood samples and defined metabolic syndrome by updated National Cholesterol Education Program criteria. We used ANOVA to test associations of adipokines with insulin resistance and multivariable logistic regression models to assess joint associations of adipokines and metabolic syndrome with insulin resistance.


METHODS
Homeostasis model (HOMA-IR), with insulin resistance defined by HOMA-IR greater than the 75th percentile, was measured.


RESULTS
Age- and sex-adjusted HOMA-IR levels were inversely related to adiponectin (r = -0.40, P < 0.0001) and positively related to resistin (r = 0.13, P < 0.0001) and TNFalpha (r = 0.12, P < 0.0001). The prevalence of insulin resistance increased with decreasing tertiles of adiponectin (from 10.9% in the third to 42.5% in the first tertile; P < 0.0001) and increasing tertiles of resistin (from 19.3 to 30.9%; P < 0.0001) and TNFalpha (from 18.8 to 32.0%; P < 0.0001). Results were similar after adjustment for body mass index. These associations were present in individuals with or without the metabolic syndrome. In multivariable regression models, metabolic syndrome and adipokines individually and jointly were significantly associated with insulin resistance.


CONCLUSIONS
Adverse levels of adipokines are associated with insulin resistance in individuals at low or high diabetes risk.
Hivert
Marie-France
MF
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA.
Sullivan
Lisa M
LM
Fox
Caroline S
CS
Nathan
David M
DM
D'Agostino
Ralph B
RB
Wilson
Peter W F
PW
Meigs
James B
JB
D052242:Adiponectin / Q000097:blood*; D000368:Aged; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D052243:Resistin / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D052242:Adiponectin; C499624:RETN protein, human; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha