title: Adjusting glucose-stimulated insulin secretion for adipose insulin resistance: an index of β-cell function in obese adults.
abstract: OBJECTIVE
  The hyperbolic relationship between insulin secretion and sensitivity has been used to assess in vivo β-cell function (i.e., the disposition index). The disposition index emphasizes the importance of taking into account both skeletal muscle and hepatic insulin resistance to depict insulin secretion. However, we propose that adipose tissue insulin resistance also needs to be accounted for when characterizing glucose-stimulated insulin secretion (GSIS) because elevated plasma free fatty acids (FFAs) impair β-cell function.
  
  
  METHODS
  To characterize the adipose disposition index, we used [1-(14)C] palmitate infusion to determine basal FFA turnover rate/adipose insulin resistance and an oral glucose tolerance test to characterize the first (i.e., 0-30 min) and second phase (i.e., 60-120 min) of GSIS. We validated a simplified version of the tracer infusion calculation as the product of (1/plasma FFA concentration × plasma insulin concentration) × GSIS in 44 obese insulin-resistant subjects.
  
  
  RESULTS
  The plasma FFA and palmitate tracer infusion calculations of the first- and second-phase disposition index were strongly correlated (r = 0.86, P < 0.000001 and r = 0.89, P < 0.000001, respectively). The first- and second-phase adipose disposition index derived from plasma FFA also was tightly associated with fasting hyperglycemia (r = -0.87, P < 0.00001 and r = -0.89, P < 0.00001, respectively) and 2-h glucose concentrations (r = -0.86, P < 0.00001 and r = -0.90, P < 0.00001).
  
  
  CONCLUSIONS
  Adjusting GSIS for adipose insulin resistance provides an index of β-cell function in obese subjects across the glucose spectrum. Plasma FFA-derived calculations of β-cell function may provide additional insight into the role of adipose tissue in glucose regulation.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Malin
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, OH.
authors.forename: Sangeeta R
authors.initials: SR
authors.lastname: Kashyap
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Jeff
authors.initials: J
authors.lastname: Hammel
authors.affiliation: University of Texas Health Science Center, Diabetes Division, San Antonio, TX.
authors.forename: Yoshi
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: University of Texas Health Science Center, Diabetes Division, San Antonio, TX kirwanj@ccf.org albarado@uthscsa.edu.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH Metabolic Translational Research Center, Endocrine and Metabolism Institute, Cleveland Clinic, Cleveland, OH kirwanj@ccf.org albarado@uthscsa.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose