Predicting Type 2 Diabetes and Testosterone Effects in high-risk Australian men: Development and external validation of a 2 year risk model

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dc.contributor.authorRobledo, K.P.
dc.contributor.authorMarschner, I.C.
dc.contributor.authorGrossmann, M.
dc.contributor.authorHandelsman, D.J.
dc.contributor.authorYeap, B.B.
dc.contributor.authorAllan, C.A.
dc.contributor.authorFoote, C.
dc.contributor.authorInder, W.J.
dc.contributor.authorStuckey, B.G.A.
dc.contributor.authorJesudason, D.
dc.contributor.authorBracken, K.
dc.contributor.authorKeech, A.C.
dc.contributor.authorJenkins, A.J.
dc.contributor.authorGebski, V.
dc.contributor.authorJardine, M.
dc.contributor.authorWittert, G.
dc.date.issued2025
dc.description.abstractObjective: We have shown that men aged 50 years+ at high risk of type 2 diabetes treated with testosterone together with a lifestyle program reduced the risk of type 2 diabetes at 2 years by 40% compared to a lifestyle program alone. To develop a personalized approach to treatment, we aimed to explore a prognostic model for incident type 2 diabetes at 2 years and investigate biomarkers predictive of the testosterone effect. Design: Model development in 783 men with impaired glucose tolerance but not type 2 diabetes from Testosterone for Prevention of Type 2 Diabetes; a multicenter, 2-year trial of Testosterone vs placebo. External validation performed in 236 men from the Examining Outcomes in Chronic Disease in the 45 and Up Study (EXTEND-45, n = 267 357). Methods: Type 2 diabetes at 2 years defined as 2-h fasting glucose by oral glucose tolerance test (OGTT) ≥11.1 mmol/L. Risk factors, including predictive biomarkers of testosterone treatment, were assessed using penalized logistic regression. Results: Baseline HbA1c and 2-h OGTT glucose were dominant predictors, together with testosterone, age, and an interaction between testosterone and HbA1c (P = .035, greater benefit with HbA1c ≥ 5.6%, 38 mmol/mol). The final model identified men who developed type 2 diabetes, with C-statistics 0.827 in development and 0.798 in validation. After recalibration, the model accurately predicted a participant’s absolute risk of type 2 diabetes. Conclusions: Baseline HbA1c and 2-h OGTT glucose predict incident type 2 diabetes at 2 years in high-risk men, with risk modified independently by testosterone treatment. Men with HbA1c ≥ 5.6% (38 mmol/mol) benefit most from testosterone treatment, beyond a lifestyle program.
dc.description.statementofresponsibilityKristy P. Robledo, Ian C. Marschner, Mathis Grossmann, David J. Handelsman, Bu B. Yeap, Carolyn A. Allan, Celine Foote, Warrick J. Inder, Bronwyn G.A. Stuckey, David Jesudason, Karen Bracken, Anthony C. Keech, Alicia J. Jenkins, Val Gebski, Meg Jardine, and Gary Wittert
dc.identifier.citationEuropean Journal of Endocrinology (EJE), 2025; 192(1):15-24
dc.identifier.doi10.1093/ejendo/lvae166
dc.identifier.issn0804-4643
dc.identifier.issn1479-683X
dc.identifier.orcidWittert, G. [0000-0001-6818-6065]
dc.identifier.urihttps://hdl.handle.net/2440/144348
dc.language.isoen
dc.publisherOxford University Press (OUP)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1030123
dc.rights© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttps://doi.org/10.1093/ejendo/lvae166
dc.subjectrisk prediction model
dc.subjectrisk prediction model validation
dc.subjectrisk score
dc.subjecttestosterone
dc.subjecttype 2 diabetes
dc.subject.meshHumans
dc.subject.meshDiabetes Mellitus, Type 2
dc.subject.meshGlucose Intolerance
dc.subject.meshTestosterone
dc.subject.meshBlood Glucose
dc.subject.meshGlucose Tolerance Test
dc.subject.meshPrognosis
dc.subject.meshRisk Assessment
dc.subject.meshRisk Factors
dc.subject.meshLife Style
dc.subject.meshAged
dc.subject.meshMiddle Aged
dc.subject.meshAustralia
dc.subject.meshMale
dc.subject.meshGlycated Hemoglobin
dc.titlePredicting Type 2 Diabetes and Testosterone Effects in high-risk Australian men: Development and external validation of a 2 year risk model
dc.typeJournal article
pubs.publication-statusPublished

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