Objectives Sex hormone-binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk. We investigated whether these associations differ by HIV and menopausal status in Black South African women living with (WLWH) and without HIV (WLWOH). Design Cross-sectional observational. Methods: Eighty one premenopausal (57 WLWOH, 24 WLWH) and 280 postmenopausal (236 WLWOH, 44 WLWH) women from the Middle-Aged Soweto Cohort (MASC) completed the following measures: circulating SHBG and sex hormones, body composition (dual energy x-ray absorptiometry), oral glucose tolerance test to estimate insulin sensitivity (Matsuda index), secretion (insulinogenic index, IGI) and clearance, and beta-cell function (disposition index, DI). Dysglycaemia was defined as either impaired fasting or postprandial glucose or T2D. Results SHBG was higher and total and free testosterone were lower in postmenopausal WLWH than WLWOH (all p<0.023). Irrespective of HIV serostatus, SHBG was positively associated with Matsuda index, insulin clearance and DI and inversely with HOMA-IR (all p<0.011). The association between SHBG and Matsuda index was stronger in premenopausal than postmenopausal women (p=0.043 for interaction). Free testosterone (and not total testosterone) was only negatively associated with basal insulin clearance (p=0.021), and positively associated with HOMA-IR in premenopausal and not post-menopausal women (p=0.015 for interaction). Conclusions We show for the first time that midlife African WLWH have higher SHBG and lower total and free testosterone than WLWOH, which corresponded to their higher beta-cell function, suggesting a putative protective effect of SHBG on T2D risk in WLWH.

The authors have declared no competing interest.

This study was jointly funded by the South African Medical Research Council (SAMRC) via the South African National Department of Health, the UK Medical Research Council (via the Newton Fund) and the GSK Africa Noncommunicable Disease Open Lab (grant project number ES/N013891/1) and the South African National Research Foundation (grant number UID:99108). The AWI Gen Collaborative Centre is funded by the National Human Genome Research Institute (NHGRI), the National Institute of Environmental Health Sciences (NIEHS), the Office of AIDS research (OAR) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), of the National Institutes of Health (NIH) under award number U54HG006938, as part of the H3Africa Consortium, and by the Department of Science and Innovation, South Africa, award number DST/CON 0056/2014. IDS is also supported by the United States National Institutes of Health (NIH)/Fogarty International Centre (FIC) grant No. D43TW010937 (University of Pittsburgh HIV Comorbidities Research Training Program in South Africa Pitt HRTP SA, PIs Prof. Jean B. Nachega and Prof. Soraya Seedat) and the Department of Science and Innovation (DSI)/National Research Foundation (NRF) Professional Development Programme. JHG, APL and IDS are supported by the SAMRC. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the sponsors.

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The Human Research Ethics Committee (HREC) (Medical) of the University of the Witwatersrand (clearance certificate No. M160604) gave ethical approval for this work.

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