To elucidate the contribution of insulin resistance to substrate utilization, insulin sensitivity and substrate oxidation were examined in 19 cancer patients and five normal controls using the euglycemic hyperinsulinemic glucose clamp technique combined with indirect calorimetry. Glucose uptake and storage were significantly decreased in cancer patients compared with that of controls. In cancer patients, both glucose storage and oxidation were positively correlated with metabolized glucose as measured by the M value in cancer patients. Decrease in glucose uptake was mainly a reflection of decreased glucose storage rather than glucose oxidation. Inversely fat oxidation was negatively correlated with both the M value and glucose oxidation in cancer patients. In cancer patients with insulin resistance, decreased glucose uptake was closely associated with a rapid decrease in glucose storage, an increase in fat oxidation and a mild decrease in glucose oxidation, suggesting that insulin resistance was connected with the alterations of substrate utilization which may induce host depletion.