How to Measure Adipose Tissue Insulin Sensitivity.
OBJECTIVE
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).


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.|Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus C, Denmark.|The Danish Diabetes Academy, 5000 Odense C, Denmark.
Esben
E
Søndergaard
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.|Facultad de Medicina, Universidad de Panamá, Panama City, Republic of Panama.
Ana Elena
AE
Espinosa De Ycaza
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.|Nutrition and Dietetics, Viterbo University, La Crosse, Wisconsin 54601.
Maria
M
Morgan-Bathke
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.
Michael D
MD
Jensen
D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism*; D000328:Adult; D005215:Fasting / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010168:Palmitates / Q000737:chemistry; D055815:Young Adult
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010168:Palmitates