2027-LB: Optimal Measures of Insulin-Regulated Lipolysis in Humans

Introduction & Objective: The euglycemic, hyperinsulinemic clamp is considered the best approach to assess insulin action. We measured free fatty acid (FFA) release rates as a function of insulin concentrations. This data was analyzed to identify the optimal insulin infusion rate(s) to measure adipose tissue insulin resistance.

Methods: Twenty-seven volunteers, age 18 - 50, underwent two-step insulin clamp studies; 5 patients undergoing bariatric surgery and 22 enrolled in a weight loss lifestyle intervention program. The baseline BMI for the bariatric surgery and lifestyle studies were 30 - 38 kg/m² and 40 - 50 kg/m², respectively. Palmitate kinetics were measured with intravenous infusion of [U-¹³C]palmitate; the low and high dose insulin infusion rates for obese volunteers were 0.25 and 0.5 mU•kg^-1•min^-1. Each dose was administered for 2.5 h and plasma glucose concentrations were maintained at 90 - 95 mg/dL using with intravenous dextrose. We used the insulin concentration resulting in 50% suppression from baseline FFA-palmitate release (IC₅₀) as the measure of adipose insulin resistance.

Results: We calculated IC₅₀ using plasma insulin concentrations measured under baseline, low and high insulin dose (IC₅₀ BLH), baseline and low insulin dose (IC₅₀ BL), or baseline and high insulin dose (IC₅₀ BH) conditions. The IC₅₀ BL values were less than IC₅₀ BLH for 34 of 50 multi-step insulin clamp studies, indicating that the IC₅₀ BLH value underestimated insulin sensitivity. Furthermore, the pattern of difference was such that relative underestimate of insulin sensitivity using the IC₅₀ BLH vs. IC₅₀ BL approach was greatest in those who were most insulin sensitive. IC₅₀ BH was generally greater than IC₅₀ BLH.

Conclusion: Optimal assessment of adipose insulin regulation of FFA release is obtained using a multi-step insulin clamp with a low insulin dose. The IC₅₀ BLH approach needs to be scrutinized, especially in insulin sensitive individuals, to be able to detect small differences or changes in adipose tissue insulin action.