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

• Published in: Andrology (Oxford) Vol. 6; no. 6; pp. 846 - 853
• Main Authors: Ramachandran, S., Strange, R. C., Fryer, A. A., Saad, F., Hackett, G. I.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-11-2018
• Subjects: Age; Age Factors; Aged; Biomarkers - blood; Cause of Death; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - mortality; England - epidemiology; Humans; Male; Middle Aged; Mortality; Prognosis; Risk Assessment; Risk Factors; Sex Hormone-Binding Globulin - analysis; sex hormone‐binding globulin; statins; Testosterone; Testosterone - blood; Time Factors; type 2 diabetes; England; mortality; type 2 diabetes; testosterone; sex hormone-binding globulin; statins; age
• ISSN: 2047-2919; 2047-2927
• DOI: 10.1111/andr.12520

Background
Serum sex hormone‐binding globulin levels have been associated with mortality in adult men with type 2 diabetes (T2DM).
Objectives
To confirm the association of serum sex hormone‐binding globulin with mortality and then determine whether this association is mediated by age and total testosterone concentration.
Materials and Methods
We studied 364 men (median age: 66 years) with T2DM over a median follow‐up of 4.3 years using the Cox regression to study associations between sex hormone‐binding globulin, age, total testosterone, and mortality.
Results
Mortality was significantly and independently associated with sex hormone‐binding globulin, age, and total testosterone. In pairwise combinations of age and sex hormone‐binding globulin dichotomized by median values, the association of sex hormone‐binding globulin with mortality was age‐dependent. Relative to the combination of age >66 years/SHBG >35 nmol/L (mortality 22.5%), the other combinations were associated with significantly less mortality (mortality in men ≤66 years/SHBG ≤ 35 nmol/L was 3.23%). In men >66 years, SHBG ≤ 35 nmol/L was associated with decreased mortality (HR: 0.41, p = 0.037) compared with SHBG > 35 nmol/L. In men ≤66 years, there was no significant difference between those with sex hormone‐binding globulin above or below the median (HR: 1.73, p = 0.56, reference: SHBG ≤ 35 nmol/L). TT < 12 nmol/L was associated with increased mortality in both age categories. Men >66 years with the reference combination of SHBG > 35 nmol/L and TT < 12 nmol/L (36.84%) nmol/L had significantly higher mortality than those with SHBG > 35 nmol/L and TT ≥ 12 (18.06%) and those with SHBG ≤ 35 nmol/L and TT < 12 nmol/L (13.79%).
Discussion
Our data suggest sex hormone‐binding globulin and total testosterone have particular impact on mortality in men aged over 66 years. Further, in older men, the combination of high sex hormone‐binding globulin levels and low total testosterone is associated with greater risk than either high sex hormone‐binding globulin or low total testosterone individually.
Conclusions
Our findings are compatible with data suggesting the importance of sex hormone‐binding globulin lies in mediating free testosterone levels.