Adjusting glucose-stimulated insulin secretion for adipose insulin resistance: An index of β-cell function in obese adults

Steven K. Malin, Sangeeta R. Kashyap, Jeff Hammel, Yoshi Miyazaki, Ralph A. DeFronzo, John P. Kirwan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

OBJECTIVE: The hyperbolic relationship between insulin secretion and sensitivity has been used to assess in vivo b-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. RESEARCH DESIGN AND METHODS: To characterize the adipose disposition index, we used [1-14C] 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 3 plasma insulin concentration) 3 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 = 20.87, P < 0.00001 and r = 20.89, P < 0.00001, respectively) and 2-h glucose concentrations (r = 20.86, P < 0.00001 and r = 20.90, P < 0.00001). CONCLUSIONS: Adjusting GSIS for adipose insulin resistance provides an index of b-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.

Original languageEnglish (US)
Pages (from-to)2940-2946
Number of pages7
JournalDiabetes care
Volume37
Issue number11
DOIs
StatePublished - Nov 1 2014

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Fingerprint Dive into the research topics of 'Adjusting glucose-stimulated insulin secretion for adipose insulin resistance: An index of β-cell function in obese adults'. Together they form a unique fingerprint.

Cite this