Standardized mixed-meal tolerance and arginine stimulation tests provide reproducible and complementary measures of β-cell function

Results from the foundation for the national institutes of health biomarkers consortium investigative series

Sudha S. Shankar, Adrian Vella, Ralph H. Raymond, Myrlene A. Staten, Roberto A. Calle, Richard N. Bergman, Charlie Cao, Danny Chen, Claudio Cobelli, Chiara Dalla Man, Mark Deeg, Jennifer Q. Dong, Douglas S. Lee, David Polidori, R. Paul Robertson, Hartmut Ruetten, Darko Stefanovski, Maria T. Vassileva, Gordon C. Weir, David A. Fryburg

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

OBJECTIVE Standardized, reproducible, and feasible quantification of b-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS FromtheMMTT, insulin secretion in T2DMwas >86%lower comparedwith NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use.

Original languageEnglish (US)
Pages (from-to)1602-1613
Number of pages12
JournalDiabetes Care
Volume39
Issue number9
DOIs
StatePublished - Sep 1 2016

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National Institutes of Health (U.S.)
Meals
Arginine
Biomarkers
Insulin
Prediabetic State
Glucose
Glucose Tolerance Test
Type 2 Diabetes Mellitus
Population

ASJC Scopus subject areas

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

Cite this

Standardized mixed-meal tolerance and arginine stimulation tests provide reproducible and complementary measures of β-cell function : Results from the foundation for the national institutes of health biomarkers consortium investigative series. / Shankar, Sudha S.; Vella, Adrian; Raymond, Ralph H.; Staten, Myrlene A.; Calle, Roberto A.; Bergman, Richard N.; Cao, Charlie; Chen, Danny; Cobelli, Claudio; Man, Chiara Dalla; Deeg, Mark; Dong, Jennifer Q.; Lee, Douglas S.; Polidori, David; Robertson, R. Paul; Ruetten, Hartmut; Stefanovski, Darko; Vassileva, Maria T.; Weir, Gordon C.; Fryburg, David A.

In: Diabetes Care, Vol. 39, No. 9, 01.09.2016, p. 1602-1613.

Research output: Contribution to journalArticle

Shankar, SS, Vella, A, Raymond, RH, Staten, MA, Calle, RA, Bergman, RN, Cao, C, Chen, D, Cobelli, C, Man, CD, Deeg, M, Dong, JQ, Lee, DS, Polidori, D, Robertson, RP, Ruetten, H, Stefanovski, D, Vassileva, MT, Weir, GC & Fryburg, DA 2016, 'Standardized mixed-meal tolerance and arginine stimulation tests provide reproducible and complementary measures of β-cell function: Results from the foundation for the national institutes of health biomarkers consortium investigative series', Diabetes Care, vol. 39, no. 9, pp. 1602-1613. https://doi.org/10.2337/dc15-0931
Shankar, Sudha S. ; Vella, Adrian ; Raymond, Ralph H. ; Staten, Myrlene A. ; Calle, Roberto A. ; Bergman, Richard N. ; Cao, Charlie ; Chen, Danny ; Cobelli, Claudio ; Man, Chiara Dalla ; Deeg, Mark ; Dong, Jennifer Q. ; Lee, Douglas S. ; Polidori, David ; Robertson, R. Paul ; Ruetten, Hartmut ; Stefanovski, Darko ; Vassileva, Maria T. ; Weir, Gordon C. ; Fryburg, David A. / Standardized mixed-meal tolerance and arginine stimulation tests provide reproducible and complementary measures of β-cell function : Results from the foundation for the national institutes of health biomarkers consortium investigative series. In: Diabetes Care. 2016 ; Vol. 39, No. 9. pp. 1602-1613.
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abstract = "OBJECTIVE Standardized, reproducible, and feasible quantification of b-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS FromtheMMTT, insulin secretion in T2DMwas >86{\%}lower comparedwith NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50{\%}) to T2DM (93{\%} lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58{\%}; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use.",
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T1 - Standardized mixed-meal tolerance and arginine stimulation tests provide reproducible and complementary measures of β-cell function

T2 - Results from the foundation for the national institutes of health biomarkers consortium investigative series

AU - Shankar, Sudha S.

AU - Vella, Adrian

AU - Raymond, Ralph H.

AU - Staten, Myrlene A.

AU - Calle, Roberto A.

AU - Bergman, Richard N.

AU - Cao, Charlie

AU - Chen, Danny

AU - Cobelli, Claudio

AU - Man, Chiara Dalla

AU - Deeg, Mark

AU - Dong, Jennifer Q.

AU - Lee, Douglas S.

AU - Polidori, David

AU - Robertson, R. Paul

AU - Ruetten, Hartmut

AU - Stefanovski, Darko

AU - Vassileva, Maria T.

AU - Weir, Gordon C.

AU - Fryburg, David A.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - OBJECTIVE Standardized, reproducible, and feasible quantification of b-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS FromtheMMTT, insulin secretion in T2DMwas >86%lower comparedwith NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use.

AB - OBJECTIVE Standardized, reproducible, and feasible quantification of b-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS FromtheMMTT, insulin secretion in T2DMwas >86%lower comparedwith NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use.

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