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Comprehensive validation of fasting-based and oral glucose tolerance test-based indices of insulin secretion against gold standard measures
Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard Karls Universität Tübingen, Tubingen, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tubingen, Germany.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.ORCID iD: 0000-0001-9016-1139
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2022 (English)In: BMJ Open Diabetes Research & Care, ISSN 2052-4897, Vol. 10, no 5, article id e002909Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: With pre-diabetes and diabetes increasingly recognized as heterogeneous conditions, assessment of beta-cell function is gaining clinical importance to identify disease subphenotypes. Our study aims to comprehensively validate all types of surrogate indices based on oral glucose tolerance test (OGTT) and fasting measurements in comparison with gold standard methods.

RESEARCH DESIGN AND METHODS: The hyperglycemic clamp extended with glucagon-like peptide 1 (GLP-1) infusion and intravenous glucose tolerance test (IVGTT), as well as OGTT, was performed in two well-phenotyped cohorts. The gold standard-derived indices were compared with surrogate insulin secretion markers, derived from fasting state and OGTT, using both Pearson's and Spearman's correlation coefficients. The insulin-based and C-peptide-based indices were analyzed separately in different groups of glucose tolerance and the entire cohorts.

RESULTS: The highest correlation coefficients were found for area under curve (AUC) (I0-30)/AUC (G0-30), I30/G30, first-phase Stumvoll and Kadowaki model. These indices have high correlation coefficients with measures obtained from both insulin and C-peptide levels from IVGTT and hyperglycemic clamp. AUC (I0-120)/AUC (G0-120), BIGTT-AIR0-60-120, I30/G30, first-phase Stumvoll and AUC (I0-30)/AUC (G0-30) demonstrated the strongest association with incretin-stimulated insulin response.

CONCLUSIONS: We have identified glucose-stimulated and GLP-1-stimulated insulin secretion indices, derived from OGTT and fasting state, that have the strongest correlation with gold standard measures and could be potentially used in future researches and clinical practice.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2022. Vol. 10, no 5, article id e002909
Keywords [en]
C-peptide, insulin, insulin secretion
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:umu:diva-199675DOI: 10.1136/bmjdrc-2022-002909ISI: 000853814700001PubMedID: 36100292Scopus ID: 2-s2.0-85137782270OAI: oai:DiVA.org:umu-199675DiVA, id: diva2:1701403
Available from: 2022-10-05 Created: 2022-10-05 Last updated: 2023-05-23Bibliographically approved

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Renklint, RebeckaChninou, YoussefOtten, Julia

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