Circulating IL-18 concentration is associated with insulin sensitivity and glucose tolerance through increased fat-free mass.
OBJECTIVE
Knowledge of the factors which simultaneously contribute to insulin-resistance-related inflammation may contribute to early therapeutic targeting. IL-18 has recently been described as one of the factors which, in addition to insulin resistance, may also contribute to atherosclerosis. However, the source of IL-18 is not well characterised.


METHODS
We aimed to study body composition (bioelectric impedance), glucose tolerance (OGTT) and insulin sensitivity (minimal model method) in relation to serum IL-18 (ELISA) concentration in 144 otherwise healthy men aged 51.9+/-12.5 years.


RESULTS
In contrast to previous observations in women, circulating IL-18 was not significantly associated with BMI (r=0.12, p=0.1) or WHR (r=0.08, p=0.3). IL-18 was also not associated with absolute or percent fat mass (bioelectric impedance, p>0.20) but, interestingly, it was significantly linked to fat-free mass (p=0.03). Serum IL-18 increased with each quartile of fat-free mass, corresponding to values of < or = 64.2; >64.2 to < or = 71.6; >71.6 to < or = 80.9; and > or = 80.9 kg (ANOVA, p<0.0001). IL-18 was more closely associated with postload glucose during an OGTT (p=0.04) rather than with fasting glucose (p=0.1). HbA1c (p=0.03), HDL-cholesterol (p=0.04) and serum triglycerides (p=0.03) and parameters of systemic inflammation (C-reactive protein, p=0.02) were also significantly associated with circulating IL-18. Insulin sensitivity (minimal model analysis) was linked to circulating IL-18 (p=0.01). In a multiple linear regression analysis this relationship remained significant after controlling for BMI, age and glucose tolerance status. In another model, both fat-free mass and insulin sensitivity contributed to 10% of IL-18 variance.


CONCLUSIONS
Fat mass does not seem to influence circulating IL-18, as initially proposed. In contrast, the fat-free mass compartment (a well-known confounder in the evaluation of insulin sensitivity) may significantly contribute to the relationship between IL-18 and insulin action.
Bosch
M
M
Section of Diabetes, Endocrinology and Nutrition, University Hospital of Girona, Dr Josep Trueta, Girona, Spain.
Lopez-Bermejo
A
A
Vendrell
J
J
Musri
M
M
Ricart
W
W
Fernandez-Real
J-M
JM
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000328:Adult; D001786:Blood Glucose / Q000502:physiology*; D001823:Body Composition; D015992:Body Mass Index; D049628:Body Size; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000502:physiology*; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002097:C-Reactive Protein; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D007328:Insulin; D020382:Interleukin-18; D014280:Triglycerides