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Hammel, M.C.* ; Stein, R. ; Kratzsch, J.* ; Vogel, M.* ; Eckert, A.J.* ; Triatin, R.D.* ; Colombo, M.* ; Meigen, C.* ; Baber, R.* ; Stanik, J.* ; Spielau, U.* ; Stoltze, A.* ; Wirkner, K.* ; Tönjes, A.* ; Snieder, H.* ; Holl, R.W.* ; Stumvoll, M.* ; Blüher, M. ; Kiess, W.* ; Körner, A.

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

Lancet Reg. Health-Eur. 30:100652 (2023)

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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: German Research Foundation (DFG)-through SFB 1052, project number 209933838, subproject C5; Federal Ministry of Education and Research, Germany; European Union-European 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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Childhood Obesity ; Homa-ir ; Insulin Resistance ; Insulin Sensitivity ; Mcauley Index ; Obesity ; Prediabetes ; Reference Values ; Type 2 Diabetes; Homeostasis Model Assessment; Body-mass Index; Plasma-glucose; Resistance; Population; Childhood; Cohort

ISSN (print) / ISBN 2666-7762

e-ISSN 2666-7762

Journal The Lancet Regional Health - Europe

Quellenangaben Volume: 30, Article Number: 100652

Publisher Elsevier

Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants German Diabetes Association
German Research Foundation (DFG)
German Center for Diabetes Research (DZD)
EU-IMI2-Consortium SOPHIA
Indonesian Endowment Fund for Education
University of Leipzig
Leipzig Research Center for Civilization Diseases (LIFE Child)
Federal Ministry of Education and Research, Germany
German Research Foundation for the Clinical Research Center "Obesity Mechanisms"
Free State of Saxony