Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.

<h4>Background</h4>To date, fasting state- and different oral glucose tolerance test (OGTT)-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced) f...

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Autores principales:	Silke A Herzberg-Schäfer, Harald Staiger, Martin Heni, Caroline Ketterer, Martina Guthoff, Konstantinos Kantartzis, Fausto Machicao, Norbert Stefan, Hans-Ulrich Häring, Andreas Fritsche
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Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
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spelling	oai:doaj.org-article:1e925f5541b4403ebc670dc3852676692021-11-18T07:02:08ZEvaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.1932-620310.1371/journal.pone.0014194https://doaj.org/article/1e925f5541b4403ebc670dc3852676692010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21152029/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>To date, fasting state- and different oral glucose tolerance test (OGTT)-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced) fasting state-/OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction.<h4>Methodology/principal findings</h4>A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms (SNPs) known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures (p≤0.05). The indices were ranked according to their associations' statistical power, and the ranks an index obtained for its associations with all the tested SNPs (or a subset) were summed up resulting in a final ranking. This approach revealed area under the curve (AUC)(Insulin(0-30))/AUC(Glucose(0-30)) as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUC(Insulin(0-30))/AUC(Glucose(0-30)), corrected insulin response (CIR), AUC(C-Peptide(0-30))/AUC(Glucose(0-30)), AUC(C-Peptide(0-120))/AUC(Glucose(0-120)), two different formulas for the incremental insulin response from 0-30 min, i.e., the insulinogenic indices (IGI)(2) and IGI(1), and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function (HOMA-B; p<0.05). AUC(C-Peptide(0-120))/AUC(Glucose(0-120)) was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last.<h4>Conclusions/significance</h4>With AUC(Insulin(0-30))/AUC(Glucose(0-30),) CIR, AUC(C-Peptide(0-30))/AUC(Glucose(0-30)), AUC(C-Peptide(0-120))/AUC(Glucose(0-120)), IGI(2), IGI(1), and insulin 30 min, dynamic measures of insulin secretion based on early insulin and C-peptide responses to oral glucose represent measures which are more appropriate to assess genetically determined β-cell dysfunction than fasting measures, i.e., HOMA-B. Genes predominantly influencing the incretin axis may possibly be best detected by AUC(C-Peptide(0-120))/AUC(Glucose(0-120)).Silke A Herzberg-SchäferHarald StaigerMartin HeniCaroline KettererMartina GuthoffKonstantinos KantartzisFausto MachicaoNorbert StefanHans-Ulrich HäringAndreas FritschePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e14194 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Silke A Herzberg-Schäfer Harald Staiger Martin Heni Caroline Ketterer Martina Guthoff Konstantinos Kantartzis Fausto Machicao Norbert Stefan Hans-Ulrich Häring Andreas Fritsche Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.
description	<h4>Background</h4>To date, fasting state- and different oral glucose tolerance test (OGTT)-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced) fasting state-/OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction.<h4>Methodology/principal findings</h4>A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms (SNPs) known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures (p≤0.05). The indices were ranked according to their associations' statistical power, and the ranks an index obtained for its associations with all the tested SNPs (or a subset) were summed up resulting in a final ranking. This approach revealed area under the curve (AUC)(Insulin(0-30))/AUC(Glucose(0-30)) as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUC(Insulin(0-30))/AUC(Glucose(0-30)), corrected insulin response (CIR), AUC(C-Peptide(0-30))/AUC(Glucose(0-30)), AUC(C-Peptide(0-120))/AUC(Glucose(0-120)), two different formulas for the incremental insulin response from 0-30 min, i.e., the insulinogenic indices (IGI)(2) and IGI(1), and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function (HOMA-B; p<0.05). AUC(C-Peptide(0-120))/AUC(Glucose(0-120)) was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last.<h4>Conclusions/significance</h4>With AUC(Insulin(0-30))/AUC(Glucose(0-30),) CIR, AUC(C-Peptide(0-30))/AUC(Glucose(0-30)), AUC(C-Peptide(0-120))/AUC(Glucose(0-120)), IGI(2), IGI(1), and insulin 30 min, dynamic measures of insulin secretion based on early insulin and C-peptide responses to oral glucose represent measures which are more appropriate to assess genetically determined β-cell dysfunction than fasting measures, i.e., HOMA-B. Genes predominantly influencing the incretin axis may possibly be best detected by AUC(C-Peptide(0-120))/AUC(Glucose(0-120)).
format	article
author	Silke A Herzberg-Schäfer Harald Staiger Martin Heni Caroline Ketterer Martina Guthoff Konstantinos Kantartzis Fausto Machicao Norbert Stefan Hans-Ulrich Häring Andreas Fritsche
author_facet	Silke A Herzberg-Schäfer Harald Staiger Martin Heni Caroline Ketterer Martina Guthoff Konstantinos Kantartzis Fausto Machicao Norbert Stefan Hans-Ulrich Häring Andreas Fritsche
author_sort	Silke A Herzberg-Schäfer
title	Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.
title_short	Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.
title_full	Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.
title_fullStr	Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.
title_full_unstemmed	Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.
title_sort	evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/1e925f5541b4403ebc670dc385267669
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Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.

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