Insulin dose response analysis of free fatty acid kinetics

Insulin regulation of free fatty acid (FFA) release is an important aspect of metabolic function; however, FFA release is exquisitely sensitive to insulin, which complicates the design and analysis of dose response experiments. We measured FFA ([³H]palmitate) and glucose ([³H]glucose) kinetics in 7 nonobese men, 7 nonobese women, 7 obese men, and 7 obese women by using a two-step insulin clamp (0.25 and 2.5 mU/kg fat-free mass per minute). Obese men and women were characterized as having a BMI of 28 or greater and body fat of 28% and 40% or greater for men and for women, respectively. Nonobese men and women had 22% and 35% or less body fat, respectively. All volunteers were Caucasian. Glucose disposal increased in a linear fashion with plasma insulin concentrations. The nonlinear suppression of plasma palmitate flux and concentrations could be linearized by logarithmically transforming both the insulin concentration and palmitate axes, except in nonobese men. We repeated the studies in 7 nonobese and 7 obese men, using 1.0 mU/kg fat-free mass per minute as the second insulin dose, which linearized the log-transformed lipolysis measures. The indices of insulin regulation of lipolysis predicted using 2 points (basal and second insulin dose) vs 3 points (basal, low, and high dose) were not different provided the proper second dose was selected. The EC₅₀ for insulin suppression of lipolysis correlated linearly with plasma triglycerides (r = 0.52, P < .001) and exponentially with insulin sensitivity_glucose (r = 0.70, P < .001). We conclude that log transformation of insulin dose response data for FFA permits straightforward data analysis and simplifies the estimation of metabolically relevant parameters.