Low SHBG is related to increased liver fat, which mediates a small part of the association between SHBG and T2D - Nederlandse Vereniging voor Endocrinologie

Background

Low levels of sex hormone binding globulin (SHBG) and fatty liver are related to an increased risk of type 2 diabetes (T2D). Our aim was to examine the relation between SHBG, liver fat content and T2D in middle aged women and men.

Methods

In the Netherlands Epidemiology of Obesity study, a population based cohort study, SHBG was measured in 5722 middle-aged men and women (53%) without pre-existing diabetes. Liver fat content was assessed by proton-MR spectroscopy in a random subgroup (n=1834). Participants were followed for the occurrence of T2D. We examined sex-stratified associations between quartiles of SHBG and liver fat with linear regression, and with T2D using Cox regression, adjusted for age, total body fat, smoking, physical activity, menopause, and hormone use. The mediating role of liver fat was studied by including liver fat in the adjusted Cox regression models and calculating the percentage mediation.

Results

The median (IQR) SHBG was 47 nmol/L (34-64) in women and 34 nmol/L (26-43) in men. Median (IQR) liver fat was 3.4% (1.6-8.2) in women and 6.0% (2.9-13.3) in men. In participants in the 4^th quartile of SHBG liver fat content was 66% (95%CI 71-59) lower in women and 37% (46-26) lower in men than in participants in the first quartile of SHBG. Participants were followed for 5.9 years (IQR 5.9-7.9). The incidence rate for T2D in women with SHBG in the 4^th quartile was 2/1000 person years (py) and 7/1000 py in men, in quartile 1 it was 15/1000 py in women and 11/1000 py in men. Compared with the first quartile of SHBG, the hazard ratio (HR, 95%CI) to develop T2D in participants in quartile 4 was 0.22 (0.11-0.44) in women and 0.55 (0.34-0.89) in men. After additional adjustment for liver fat, the HRs were 0.29 (0.06-1.40) in women 0.62 (0.28-1.41) in men, reflecting a percentage mediation of 10% in women and 24% in men.

Conclusion:

In middle aged women and men, low SHBG levels were associated with increased liver fat and an increased risk of T2D. The amount of liver fat mediated a small part of the association between SHBG and T2D.