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An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling

Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness at zero insulin (GEZI) using intravenous gluc...

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Autores principales: Hu, Shihao, Lu, Yuzhi, Tura, Andrea, Pacini, Giovanni, D’Argenio, David Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039510/
https://www.ncbi.nlm.nih.gov/pubmed/33854483
http://dx.doi.org/10.3389/fendo.2021.641713
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author Hu, Shihao
Lu, Yuzhi
Tura, Andrea
Pacini, Giovanni
D’Argenio, David Z.
author_facet Hu, Shihao
Lu, Yuzhi
Tura, Andrea
Pacini, Giovanni
D’Argenio, David Z.
author_sort Hu, Shihao
collection PubMed
description Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness at zero insulin (GEZI) using intravenous glucose tolerance test data from subjects with type 2 diabetes (T2D, n=154) and non-diabetic (ND) subjects (n=343). A hierarchical statistical analysis was performed, which provided a formal mechanism for pooling the data from all study subjects, to yield a single composite population model that quantifies the role of subject specific characteristics such as weight, height, age, sex, and glucose tolerance. Based on the resulting composite population model, GEZI was reduced from 0.021 min(–1) (standard error – 0.00078 min(–1)) in the ND population to 0.011 min(–1) (standard error – 0.00045 min(–1)) in T2D. The resulting model was also employed to calculate the proportion of the non–insulin-dependent net glucose uptake in each subject receiving an intravenous glucose load. Based on individual parameter estimates, the fraction of total glucose disposal independent of insulin was 72.8% ± 12.0% in the 238 ND subjects over the course of the experiment, indicating the major contribution to the whole-body glucose clearance under non-diabetic conditions. This fraction was significantly reduced to 48.8% ± 16.9% in the 30 T2D subjects, although still accounting for approximately half of the total in the T2D population based on our modeling analysis. Given the potential application of glucose effectiveness as a predictor of glucose intolerance and as a potential therapeutic target for treating diabetes, more investigations of glucose effectiveness in other disease conditions can be conducted using the hierarchical modeling framework reported herein.
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spelling pubmed-80395102021-04-13 An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling Hu, Shihao Lu, Yuzhi Tura, Andrea Pacini, Giovanni D’Argenio, David Z. Front Endocrinol (Lausanne) Endocrinology Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness at zero insulin (GEZI) using intravenous glucose tolerance test data from subjects with type 2 diabetes (T2D, n=154) and non-diabetic (ND) subjects (n=343). A hierarchical statistical analysis was performed, which provided a formal mechanism for pooling the data from all study subjects, to yield a single composite population model that quantifies the role of subject specific characteristics such as weight, height, age, sex, and glucose tolerance. Based on the resulting composite population model, GEZI was reduced from 0.021 min(–1) (standard error – 0.00078 min(–1)) in the ND population to 0.011 min(–1) (standard error – 0.00045 min(–1)) in T2D. The resulting model was also employed to calculate the proportion of the non–insulin-dependent net glucose uptake in each subject receiving an intravenous glucose load. Based on individual parameter estimates, the fraction of total glucose disposal independent of insulin was 72.8% ± 12.0% in the 238 ND subjects over the course of the experiment, indicating the major contribution to the whole-body glucose clearance under non-diabetic conditions. This fraction was significantly reduced to 48.8% ± 16.9% in the 30 T2D subjects, although still accounting for approximately half of the total in the T2D population based on our modeling analysis. Given the potential application of glucose effectiveness as a predictor of glucose intolerance and as a potential therapeutic target for treating diabetes, more investigations of glucose effectiveness in other disease conditions can be conducted using the hierarchical modeling framework reported herein. Frontiers Media S.A. 2021-03-29 /pmc/articles/PMC8039510/ /pubmed/33854483 http://dx.doi.org/10.3389/fendo.2021.641713 Text en Copyright © 2021 Hu, Lu, Tura, Pacini and D’Argenio https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Hu, Shihao
Lu, Yuzhi
Tura, Andrea
Pacini, Giovanni
D’Argenio, David Z.
An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling
title An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling
title_full An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling
title_fullStr An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling
title_full_unstemmed An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling
title_short An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling
title_sort analysis of glucose effectiveness in subjects with or without type 2 diabetes via hierarchical modeling
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039510/
https://www.ncbi.nlm.nih.gov/pubmed/33854483
http://dx.doi.org/10.3389/fendo.2021.641713
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