SHBG, testosterone and type 2 diabetes risk in middle-aged African women: exploring the impact of HIV and menopause.

Abstract

Context: Sex hormone-binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk.

Objective: To investigate whether the associations between SHBG, testosterone and T2D risk differ by HIV and menopausal status in Black African women living with (WH) and without HIV (WOH).

Design: Cross-sectional observational.

Setting: Health Research Unit in Soweto, Johannesburg, South Africa.

Participants: 81 premenopausal (57 WOH, 24 WH) and 280 postmenopausal (236 WOH, 44 WH) women from the Middle-Aged Soweto Cohort (MASC).

Main outcome measures: Circulating SHBG and sex hormones, body composition (dual energy x-ray absorptiometry), 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 WH than WOH (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 WH have higher SHBG and lower total and free testosterone than WOH, which corresponded to their higher beta-cell function, suggesting a putative protective effect of SHBG on T2D risk in WH.