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The association of sex hormone binding globulin with mortality is mediated by age in men with type 2 diabetes

Ramachandran, S1; Strange, RC2; Fryer, AA3; Hackett, GI1

1: Heart of England NHS Foundation Trust, United Kingdom; 2: Institute for Science and Technology in Medicine, Keele University, United Kingdom ; 3: University Hopsitals of North Midlands, United Kingdom

Objective: Hypogonadism (HG), characterised by low serum testosterone and sexual dysfunction, is common in men with diabetes and is independent determinants of CVD risk and mortality. While sex hormone binding globulin (SHBG), lower levels associated with type 2 diabetes (T2DM), was previously considered a passive carrier of sex steroids, recent data suggests that higher levels may be associated with increased mortality. We now describe studies on the relationship between mortality, age and SHBG.

Material and Methods: We studied 364 men with T2DM not receiving testosterone replacement therapy over a mean 4.2 year; 44 deaths were observed. The primary outcome was all-cause mortality and the association with baseline SHBG levels determined via Cox survival analysis. The statistical model including other factors such as baseline testosterone concentration and other factors associated with SHBG levels.

Results: Higher SHBG was seen to be associated with increased body mass index, HbA1c, triglycerides and lower HDL-cholesterol; this finding was expected in our diabetic cohort. SHBG was positively correlated with all-cause mortality (HR: 1.02, 95% CI: 1.01 – 1.04, p=0.007). This association remained significant (HR: 1.03, 95% CI: 1.01 – 1.04, p=0.001) in a model that included other factors associated with mortality such as age, baseline total testosterone (or calculated free testosterone) and triglycerides (all these factors were also associated with mortality suggesting independent effects). We then used pairwise combinations of SHBG and age at recruitment, categorised by median values (age: 66 years, SHBG: 35nmol/l). This analysis showed that association between SHBG and mortality was evident only in men over 66 years; SHBG > 35nmol/l demonstrated higher mortality (mortality: 22.45% , HR: 2.44, 95% CI: 1.05 – 5.56, p=0.077) than SHBG ≤ 35nmol/l (mortality: 15.79%). This effect was independent of both baseline testosterone and triglycerides.

Conclusions: Our data support previous research showing SHBG to be associated with mortality in men with T2DM. We extended these findings by showing, for the first time, that this association is mediated by age; it was only found in men aged >66 years.


Work supported by industry: yes, by Bayer UK (industry funding only - investigator initiated and executed study).

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