SHBG, Free Testosterone, and Type 2 Diabetes Risk in Middle-aged African Men: A Longitudinal Study

Author:

Seipone Ikanyeng D1ORCID,Mendham Amy E234,Storbeck Karl-Heinz5ORCID,Oestlund Imken5,Kufe Clement N3,Chikowore Tinashe3,Masemola Maphoko3,Crowther Nigel J6,Kengne Andre Pascal7,Norris Shane3,Olsson Tommy8ORCID,Brown Todd9ORCID,Micklesfield Lisa K3,Goedecke Julia H13ORCID

Affiliation:

1. Biomedical Research Innovation Platform, South African Medical Research Council , Cape Town 7505 , South Africa

2. Riverland Academy of Clinical Excellence, Riverland Mallee Coorong Local Health Network, South Australia Health , Berri, SA 5343 , Australia country

3. South African Medical Research Council/WITS Developmental Pathways for Health Research Unit, Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg 2000 , South Africa

4. Health through Physical Activity, Lifestyle and Sport Research Centre, FIMS International Collaborating Centre of Sports Medicine, Division of Physiological Sciences, Department of Human Biology, Faculty of Health Sciences, University of Cape Town , Cape Town 7701 , South Africa

5. Department of Biochemistry, Stellenbosch University , Stellenbosch 7602 , South Africa

6. Department of Chemical Pathology, National Health Laboratory Service and University of the Witwatersrand Faculty of Health Sciences , Johannesburg 2000 , South Africa

7. Non-Communicable Diseases Research Unit, South African Medical Research Council , Cape Town 7505 , South Africa

8. Department of Public Health and Clinical Medicine, Umeå University , Umeå 90187 , Sweden

9. Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine , Baltimore, MD 21218 , USA

Abstract

Abstract Objectives 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.

Funder

South African Medical Research Council

UK Medical Research Council

South African National Research Foundation

National Institutes of Health

Fogarty International Center

National Research Foundation

National Human Genome Research Institute

National Institute of Environmental Health Sciences

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

The Endocrine Society

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