Whether visceral adipose tissue has a uniquely powerful association wi
th insulin resistance or whether subcutaneous abdominal fat shares thi
s link has generated controversy in the area of body composition and i
nsulin sensitivity. An additional issue is the potential role of fat d
eposition within skeletal muscle and the relationship with insulin res
istance. To address these matters, the current study was undertaken to
measure body composition, aerobic fitness, and insulin sensitivity wi
thin a cohort of sedentary healthy men (n = 26) and women (n = 28). Th
e subjects, who ranged from lean to obese (BMI 19.6-41.0 kg/m(2)), und
erwent dual energy X-ray absorptiometry (DEXA) to measure fat-free mas
s (FFM) and fat mass (FM), computed tomography to measure cross-sectio
nal abdominal subcutaneous and visceral adipose tissue, and computed t
omography (CT) of mid-thigh to measure muscle cross-sectional area, mu
scle attenuation, and subcutaneous fat. Insulin sensitivity was measur
ed using the glucose clamp technique (40 mU . m(-2) . min(-1)), in con
junction with [3-H-3]glucose isotope dilution. Maximal aerobic power (
VO2max) was determined using an incremental cycling test. Insulin-stim
ulated glucose disposal (R-d) ranged from 3.03 to 16.83 mg . min(-1) .
kg(-1) FFM. R-d was negatively correlated with FM (r = -0.58), viscer
al fat (r = -0.52), subcutaneous abdominal fat (r = -0.61), and thigh
fat (r = -0.38) and positively correlated with muscle attenuation (r =
0.48) and VO2max (r = 0.26, P < 0.05). In addition to manifesting the
strongest simple correlation with insulin sensitivity, in stepwise mu
ltiple regression, subcutaneous abdominal fat retained significance af
ter adjusting for visceral fat, while the converse was not found. Musc
le attenuation contributed independent significance to multiple regres
sion models of body composition and insulin sensitivity, and in analys
is of obese subjects, muscle attenuation was the strongest single corr
elate of insulin resistance. In summary, as a component of central adi
posity, subcutaneous abdominal fat has as strong an association with i
nsulin resistance as visceral fat, and altered muscle composition, sug
gestive of increased fat content, is an important independent marker o
f insulin resistance in obesity.