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 journalArticle

14 Citations (Scopus)

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

Fingerprint

Insulin Resistance
Nonesterified Fatty Acids
Insulin
Glucose
Palmitates
Adipose Tissue
Glucose Tolerance Test
Hyperglycemia
Fasting
Skeletal Muscle
Research Design
Liver

ASJC Scopus subject areas

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

Cite this

Adjusting glucose-stimulated insulin secretion for adipose insulin resistance : An index of β-cell function in obese adults. / Malin, Steven K.; Kashyap, Sangeeta R.; Hammel, Jeff; Miyazaki, Yoshi; Defronzo, Ralph A; Kirwan, John P.

In: Diabetes Care, Vol. 37, No. 11, 01.11.2014, p. 2940-2946.

Research output: Contribution to journalArticle

Malin, Steven K. ; Kashyap, Sangeeta R. ; Hammel, Jeff ; Miyazaki, Yoshi ; Defronzo, Ralph A ; Kirwan, John P. / Adjusting glucose-stimulated insulin secretion for adipose insulin resistance : An index of β-cell function in obese adults. In: Diabetes Care. 2014 ; Vol. 37, No. 11. pp. 2940-2946.
@article{0e04b039075d42099a7a6273982c9929,
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 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.",
author = "Malin, {Steven K.} and Kashyap, {Sangeeta R.} and Jeff Hammel and Yoshi Miyazaki and Defronzo, {Ralph A} and Kirwan, {John P.}",
year = "2014",
month = "11",
day = "1",
doi = "10.2337/dc13-3011",
language = "English (US)",
volume = "37",
pages = "2940--2946",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "11",

}

TY - JOUR

T1 - Adjusting glucose-stimulated insulin secretion for adipose insulin resistance

T2 - An index of β-cell function in obese adults

AU - Malin, Steven K.

AU - Kashyap, Sangeeta R.

AU - Hammel, Jeff

AU - Miyazaki, Yoshi

AU - Defronzo, Ralph A

AU - Kirwan, John P.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84910147058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84910147058&partnerID=8YFLogxK

U2 - 10.2337/dc13-3011

DO - 10.2337/dc13-3011

M3 - Article

VL - 37

SP - 2940

EP - 2946

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 11

ER -