Predicting Type 2 Diabetes and Testosterone Effects in high-risk Australian men: Development and external validation of a 2 year risk model.
Kristy 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; Gary Wittert
Abstract
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 two 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 two years and investigate biomarkers predictive of the testosterone effect. Model development in 783 men with impaired glucose tolerance but not type 2 diabetes from T4DM; 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). Type 2 diabetes at two years defined as 2-hour fasting glucose by oral glucose tolerance test (OGTT) ≥ 11.1mmol/L. Risk factors, including predictive biomarkers of testosterone treatment, were assessed using penalized logistic regression. Baseline HbA1c and 2-hour OGTT glucose were dominant predictors, together with Testosterone, age, and an interaction between Testosterone and HbA1c (p=0.035, greater benefit with HbA1c≥5.6%, 38mmol/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. Baseline HbA1c and 2-hour 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% (38mmol/mol) benefit most from Testosterone treatment, beyond a lifestyle program.
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| ISSN | 1479-683X |
| Published | 25 Dec 2024 |
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| DOI | 10.1093/ejendo/lvae166 |
| Type | Journal Article |
| Sponsorship |