Multiple indexes of lipid availability are independently related to whole body insulin action in healthy humans

An increase in muscle lipid content has been postulated to relate closely to the evolution of insulin resistance. We aimed to test whether the multiple indexes of lipid supply within man [namely, circulating triglycerides, skeletal muscle triglycerides (SMT), total and central fat mass, and circulating leptin] were independent predictors of insulin resistance, or whether triglycerides from different sources are additive in their influence on whole body insulin sensitivity. Whole body insulin sensitivity, body composition, and SMT content were determined in 49 sedentary, nondiabetic males (age, 20-74 yr; body mass index, 20-38 kg/m(2)). Insulin sensitivity was inversely associated with central abdominal fat (r(2) = 0.38; P < 0.0001), total body fat (r(2) = 0.21; P = 0.0003), SMT content (r2 = 0.16; P = 0.005), and fasting triglycerides (r(2) = 0.24; P = 0.0003), nonesterified free fatty acid (r(2) = 0.19; P = 0.002), and leptin (r(2) = 0.35; P < 0.0001) levels. However, only central abdominal fat was significantly related to SMT content (r(2) = 0.10; P = 0.03). SMT content, circulating triglycerides, and measurements of total or central adiposity were independent predictors of whole body insulin sensitivity.