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Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs

BACKGROUND: Fasting indices of glucose-insulin-metabolism are an easy and affordable tool to assess insulin resistance. We aimed to establish reference ranges for fasting insulin indices that reflect age-dependent variation over the entire life span and subsequently test their clinical application r...

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Autores principales: Hammel, Maximiliane Chiara, Stein, Robert, Kratzsch, Jürgen, Vogel, Mandy, Eckert, Alexander J., Triatin, Rima Destya, Colombo, Marco, Meigen, Christof, Baber, Ronny, Stanik, Juraj, Spielau, Ulrike, Stoltze, Anette, Wirkner, Kerstin, Tönjes, Anke, Snieder, Harold, Holl, Reinhard W., Stumvoll, Michael, Blüher, Matthias, Kiess, Wieland, Körner, Antje
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350850/
https://www.ncbi.nlm.nih.gov/pubmed/37465325
http://dx.doi.org/10.1016/j.lanepe.2023.100652
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author Hammel, Maximiliane Chiara
Stein, Robert
Kratzsch, Jürgen
Vogel, Mandy
Eckert, Alexander J.
Triatin, Rima Destya
Colombo, Marco
Meigen, Christof
Baber, Ronny
Stanik, Juraj
Spielau, Ulrike
Stoltze, Anette
Wirkner, Kerstin
Tönjes, Anke
Snieder, Harold
Holl, Reinhard W.
Stumvoll, Michael
Blüher, Matthias
Kiess, Wieland
Körner, Antje
author_facet Hammel, Maximiliane Chiara
Stein, Robert
Kratzsch, Jürgen
Vogel, Mandy
Eckert, Alexander J.
Triatin, Rima Destya
Colombo, Marco
Meigen, Christof
Baber, Ronny
Stanik, Juraj
Spielau, Ulrike
Stoltze, Anette
Wirkner, Kerstin
Tönjes, Anke
Snieder, Harold
Holl, Reinhard W.
Stumvoll, Michael
Blüher, Matthias
Kiess, Wieland
Körner, Antje
author_sort Hammel, Maximiliane Chiara
collection PubMed
description BACKGROUND: Fasting indices of glucose-insulin-metabolism are an easy and affordable tool to assess insulin resistance. We aimed to establish reference ranges for fasting insulin indices that reflect age-dependent variation over the entire life span and subsequently test their clinical application regarding the prediction of glycemic deterioration in children. METHODS: We calculated age- and puberty-dependent reference values for HOMA-IR, HOMA2-IR, HOMA-β, McAuley index, fasting insulin, and fasting glucose from 6994 observations of 5512 non-obese healthy subjects aged 5–80 years. Applying those references, we determined the prevalence of insulin resistance among 2538 subjects with obesity. Furthermore, we investigated the intraindividual stability and the predictive values for future dysglycemia of these fasting indices in 516 children and adolescents with obesity up to 19 years of follow-up. We validated the results in three independent cohorts. FINDINGS: There was a strong age-dependent variation of all indices throughout the life span, including prolonged recovery of pubertal insulin resistance and a subsequent continuous increase throughout adulthood. Already from age 5 years onwards, >40% of children with obesity presented with elevated parameters of insulin resistance. Applying newly developed reference ranges, insulin resistance among children with obesity doubled the risk for future glycemic deterioration (HOMA-IR HR 1.88 (95% CI 1.1–3.21)), fasting insulin HR 1.89 (95% CI 1.11–3.23). In contrast, fasting glucose alone was not predictive for emerging dysglycemia in children with obesity (HR 1.03 (95% CI 0.62–1.71)). The new insulin-based thresholds were superior to fasting glucose and HbA1c in detecting children eventually manifesting with dysglycemia in prospective analyses. INTERPRETATION: The variation of fasting glucose-insulin-metabolism across the life span necessitates age-specific reference ranges. The improved prediction of future glycemic deterioration by indices based on fasting insulin beyond simple glucose measures alone could help to stratify risk characteristics of children with obesity in order to guide patient-tailored prevention and intervention approaches. FUNDING: 10.13039/501100001659German Research Foundation (DFG)—through SFB 1052, project number 209933838, subproject C5; 10.13039/501100002347Federal Ministry of Education and Research, Germany; European Union–10.13039/501100008530European Regional Development Fund; Free State of Saxony. The German Diabetes Association, the CarbHealth consortium (01EA1908B). EU-IMI2-Consortium SOPHIA (grant agreement No 875534), German Center for Diabetes Research (DZD), grant number 82DZD14E03.
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spelling pubmed-103508502023-07-18 Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs Hammel, Maximiliane Chiara Stein, Robert Kratzsch, Jürgen Vogel, Mandy Eckert, Alexander J. Triatin, Rima Destya Colombo, Marco Meigen, Christof Baber, Ronny Stanik, Juraj Spielau, Ulrike Stoltze, Anette Wirkner, Kerstin Tönjes, Anke Snieder, Harold Holl, Reinhard W. Stumvoll, Michael Blüher, Matthias Kiess, Wieland Körner, Antje Lancet Reg Health Eur Articles BACKGROUND: Fasting indices of glucose-insulin-metabolism are an easy and affordable tool to assess insulin resistance. We aimed to establish reference ranges for fasting insulin indices that reflect age-dependent variation over the entire life span and subsequently test their clinical application regarding the prediction of glycemic deterioration in children. METHODS: We calculated age- and puberty-dependent reference values for HOMA-IR, HOMA2-IR, HOMA-β, McAuley index, fasting insulin, and fasting glucose from 6994 observations of 5512 non-obese healthy subjects aged 5–80 years. Applying those references, we determined the prevalence of insulin resistance among 2538 subjects with obesity. Furthermore, we investigated the intraindividual stability and the predictive values for future dysglycemia of these fasting indices in 516 children and adolescents with obesity up to 19 years of follow-up. We validated the results in three independent cohorts. FINDINGS: There was a strong age-dependent variation of all indices throughout the life span, including prolonged recovery of pubertal insulin resistance and a subsequent continuous increase throughout adulthood. Already from age 5 years onwards, >40% of children with obesity presented with elevated parameters of insulin resistance. Applying newly developed reference ranges, insulin resistance among children with obesity doubled the risk for future glycemic deterioration (HOMA-IR HR 1.88 (95% CI 1.1–3.21)), fasting insulin HR 1.89 (95% CI 1.11–3.23). In contrast, fasting glucose alone was not predictive for emerging dysglycemia in children with obesity (HR 1.03 (95% CI 0.62–1.71)). The new insulin-based thresholds were superior to fasting glucose and HbA1c in detecting children eventually manifesting with dysglycemia in prospective analyses. INTERPRETATION: The variation of fasting glucose-insulin-metabolism across the life span necessitates age-specific reference ranges. The improved prediction of future glycemic deterioration by indices based on fasting insulin beyond simple glucose measures alone could help to stratify risk characteristics of children with obesity in order to guide patient-tailored prevention and intervention approaches. FUNDING: 10.13039/501100001659German Research Foundation (DFG)—through SFB 1052, project number 209933838, subproject C5; 10.13039/501100002347Federal Ministry of Education and Research, Germany; European Union–10.13039/501100008530European Regional Development Fund; Free State of Saxony. The German Diabetes Association, the CarbHealth consortium (01EA1908B). EU-IMI2-Consortium SOPHIA (grant agreement No 875534), German Center for Diabetes Research (DZD), grant number 82DZD14E03. Elsevier 2023-05-23 /pmc/articles/PMC10350850/ /pubmed/37465325 http://dx.doi.org/10.1016/j.lanepe.2023.100652 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Hammel, Maximiliane Chiara
Stein, Robert
Kratzsch, Jürgen
Vogel, Mandy
Eckert, Alexander J.
Triatin, Rima Destya
Colombo, Marco
Meigen, Christof
Baber, Ronny
Stanik, Juraj
Spielau, Ulrike
Stoltze, Anette
Wirkner, Kerstin
Tönjes, Anke
Snieder, Harold
Holl, Reinhard W.
Stumvoll, Michael
Blüher, Matthias
Kiess, Wieland
Körner, Antje
Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs
title Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs
title_full Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs
title_fullStr Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs
title_full_unstemmed Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs
title_short Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs
title_sort fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350850/
https://www.ncbi.nlm.nih.gov/pubmed/37465325
http://dx.doi.org/10.1016/j.lanepe.2023.100652
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