1449-P: Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Diabetes: The Study of Women's Health Across the Nation (SWAN)

Abstract

Low circulating levels of sex hormone-binding globulin (SHBG), a putative marker of androgenicity, have been associated with poor glucose control in studies conducted primarily among post-menopausal women. However, the relation of long-term changes in endogenous SHBG to risk of type 2 diabetes (T2DM) in women during and after the menopause transition is unclear. We aimed to assess the longitudinal associations between SHBG levels and risk of developing T2DM among such women. We included 3,060 participants in the Study of Women’s Health Across the Nation (SWAN) who were free of diabetes at baseline. SWAN is a longitudinal cohort study with up to 17 years of follow-up. SHBG levels were measured at 13 visits. Participants reported diagnosed diabetes status at all visits, and fasting glucose was measured at 8 follow-up visits. T2DM was defined based on self-report or fasting glucose levels. Women averaged 46 (SD=3) years of age at baseline. 311 women developed T2DM during follow-up. We used complementary log-log-based discrete time survival models anchored at baseline to estimate associations of longitudinal SHBG with incident T2DM. A 5-unit (nM) increase in time-varying SHBG was associated with a hazard ratio (HR) of 0.86 (95% CI 0.82, 0.90), for T2DM, after controlling for race-ethnicity, age, cycle day of blood draw, site, time-varying body mass index (BMI), testosterone, and baseline SHBG level. After adjusting for covariates, women in the lowest ((-92.0 - -1.1 nM/year) vs. highest quartile (0.7 - 42.1 nM/year) for time-invariant average rate of change per year in SHBG levels) had a HR of 5.18 (95% CI: 3.55,7.56). No association was observed for other quartiles in rate of change of SHBG with developing T2DM. Women with low levels of SHBG and/or decreases in SHBG levels were at increased risk to develop T2DM. Clinicians should be aware that declining levels of SHBG in mid-life women is strongly associated with developing T2DM, independent known T2DM risk factors. Disclosure M.M. Hedderson: None. C. Lee: None. A. Capra: None. J. Lee: None. P. Chang: None. E. Gold: None. E. Waetjen: None. L.A. Habel: None. S.R. El Khoudary: None. Funding National Institutes of Health