Norris, ShaneSeipone, Ikanyeng D.Mendham, Amy E.Storbeck, Karl-HeinzOestlund, ImkenKufe, Clement N.Chikowore, TinasheMasemola, MaphokoCrowther, Nigel J.Kengne, Andre PascalOlsson, TommyBrown, ToddMicklesfield, Lisa K.Goedecke, Julia H.2024-08-122024-08-122024Seipone, I. D., Mendham, A. E., Storbeck, K. H., Oestlund, I., Kufe, C. N., Chikowore, T., Masemola, M., Crowther, N. J., Kengne, A. P., Norris, S., Olsson, T., Brown, T., Micklesfield, L. K., & Goedecke, J. H. (2024). SHBG, Free Testosterone, and Type 2 Diabetes Risk in Middle-aged African Men: A Longitudinal Study. Journal of the Endocrine Society, 8(8), bvae129. https://doi.org/10.1210/jendso/bvae1292472-1972 (online)https://hdl.handle.net/10539/40058Objectives: To investigate longitudinal changes in SHBG and free testosterone (free T) levels among Black middle-aged African men, with and without coexistent HIV, and explore associations with incident dysglycaemia and measures of glucose metabolism. Design: This longitudinal study enrolled 407 Black South African middle-aged men, comprising primarily 322 men living without HIV (MLWOH) and 85 men living with HIV (MLWH), with normal fasting glucose at enrollment. Follow-up assessments were conducted after 3.1 ± 1.5 years. Methods: At baseline and follow-up, SHBG, albumin, and total testosterone were measured and free T was calculated. An oral glucose tolerance test at follow-up determined dysglycaemia (impaired fasting glucose, impaired glucose tolerance, type 2 diabetes) and glucose metabolism parameters including insulin sensitivity (Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and beta(β)- cell function (disposition index). The primary analysis focussed on MLWOH, with a subanalysis on MLWH to explore whether associations in MLWOH differed from MLWH. Results: The prevalence of dysglycaemia at follow-up was 17% (n = 55) in MLWOH. Higher baseline SHBG was associated with a lower risk of incident dysglycaemia (odds ratio 0.966; 95% confidence interval 0.945-0.987) and positively associated with insulin sensitivity (β = 0.124, P < .001) and β-cell function (β = 0.194, P = .001) at follow-up. Free T did not predict dysglycaemia. In MLWH, dysglycaemia prevalence at follow-up was 12% (n = 10). Neither baseline SHBG nor free T were associated with incident dysglycaemia and glucose metabolism parameters in MLWH. Conclusion: SHBG levels predict the development of dysglycaemia in middle-aged African men but do not exhibit the same predictive value in MLWH.© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.Free testosteroneSex hormone-binding globulinDysglycaemiaType 2 diabetesAfricaSDG-3: Good health and well-beingArticle