Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR).

We studied insulin sensitivity in 25 adults by measuring the insulin concentration resulting in 50% suppression of palmitate flux (IC₅₀) using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-¹³C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations.

Adipo-IR was reproducible (sample coefficient of variability, 10.0%) and correlated with the IC₅₀ measured by the multistep pancreatic clamp technique (r, 0.86; P < 0.001). Age and physical fitness were significant predictors of the residual variation between Adipo-IR and IC₅₀, with a positive relationship with age (r, 0.47; P = 0.02) and a negative association with VO₂ peak (r, −0.46; P = 0.02). Likewise, IC₅₀ measured by the multistep pancreatic clamp technique correlated with IC₅₀ measured using the one-step hyperinsulinemic-euglycemic clamp technique (r, 0.73; P < 0.001).

Adipo-IR and the one-step hyperinsulinemic-euglycemic clamp technique using a palmitate tracer are good predictors of a gold standard measure of adipose tissue insulin sensitivity. However, age and physical fitness systematically affect the predictive values. Although Adipo-IR is suitable for larger population studies, the multistep pancreatic clamp technique is probably needed for mechanistic studies of adipose tissue insulin action.