The role of sex hormone-binding globulin in the risk of incident metabolic syndrome: further evidence from a longitudinal population-based sample of adult men.

R. Haring; H. Volzke; C. Spielhagen; M. Nauck; H. Wallaschofski

Background: In the classic paradigm, the primary function of sex hormone-binding globulin (SHBG) was thought to passively bind and transport steroids and estrogens in the blood to access target tissues and to determine their bioavailable fraction. Now there is increasing evidence that SHBG plays an active role in steroid actions and is an actively contributes to many age-associated comorbidities including type 2 diabetes, obesity, and metabolic syndrome (MetS).

Objective: To further evaluate the suggested independent association of SHBG with incident MetS in men.

Research Design and Methods: We used data from 956 men aged 20–79 years from the population-based Study of Health in Pomerania (SHIP). Cross-sectional and longitudinal logistic regression models with sequential adjustment for 1) age and smoking, 2) SHBG or total testosterone (TT), respectively, 3) body mass index, and 4) glycated hemoglobin were performed.

Results: In model 1) we found lower TT (odds ratio [OR] per SD decrement: 1.48 (95% CI: 1.27–1.73) p-value, <0.001) and SHBG (OR: 1.65 (1.36–2.00) p-value, <0.001) associated with incident MetS. After additional adjustment for the respective sex hormone, this association was abolished for TT (OR: 1.20 (0.99–1.46) p-value, 0.057), but not for SHBG (OR: 1.47 (1.17–1.86) p-value, 0.001).

Furthermore, p for trend analyses in fully-adjusted models showed a progressive inverse dose-response relationship for quartiles of SHBG (<0.001) and risk of incident MetS, but not across TT (0.468) or free T quartiles (0.438).

Conclusions: SHBG is a predictor of incident MetS independent of testosterone in men, but not vice versa.

Multiple logistic regression models for the risk of incident metabolic syndrome.

Table 1
			Odds ratio per SD decrease (95% CI), p-value
		Age & smoking	Age, smoking, and SHBG	Age, smoking, SHBG, and BMI	Age, smoking, SHBG, BMI, and HbA1c
Total testosterone	Cross-sectional	1.74 (1.53; 1.98), <0.001	1.50 (1.30; 1.73), <0.001	1.34 (1.16; 1.56), <0.001	1.28 (1.10; 1.50), 0.002
	Longitudinal	1.48 (1.27; 1.73), <0.001	1.20 (0.99; 1.46), 0.057	1.14 (0.93; 1.39), 0.201	1.14 (0.93; 1.39), 0.205
Free testosterone	Cross-sectional	1.35 (1.19; 1.53), <0.001	1.48 (1.29; 1.69), <0.001	1.35 (1.17; 1.56), <0.001	1.29 (1.11; 1.51), 0.001
	Longitudinal	1.02 (0.88; 1.19), 0.780	1.12 (0.96; 1.32), 0.160	1.07 (0.90; 1.27), 0.430	1.07 (0.90; 1.27), 0.439
		Age & smoking	Age, smoking, and TT	Age, smoking, TT, and BMI	Age, smoking, TT, BMI,and HbA1c
Sex hormone-binding globulin	Cross-sectional	1.68 (1.47; 1.93), <0.001	1.32 (1.15; 1.52), <0.001	1.12 (0.98; 1.27), 0.102	1.13 (0.98; 1.30), 0.083
	Longitudinal	1.65 (1.36; 2.00), <0.001	1.47 (1.17; 1.86), 0.001	1.30 (1.03; 1.65), 0.029	1.30 (1.03; 1.65), 0.028

SD, standard deviation; TT, total testosterone; SHBG, sex hormone-binding globulin; BMI, body mass index; HbA1c, glycated hemoglobin.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.

Endocrine Abstracts

P516