Abstract
BackgroundSex hormone-binding globulin (SHBG) levels and sex hormones have been implicated in the pathogenesis of type 2 diabetes and cardiovascular diseases. As fatty liver has been suggested to be a major determinant of SHBG levels, we examined whether the associations of SHBG and testosterone with diabetes were independent of fatty liver.MethodsWe conducted a case–control study that included 300 diabetes cases (215 men and 85 women) and 300 matched controls from the Saku cohort study. Diabetes was defined by either fasting plasma glucose levels ≥126 mg/dL, 2-h post-load glucose levels ≥200 mg/dL after a 75 g oral glucose tolerance test, or diabetes diagnosed by physicians. We fitted conditional logistic regression models to examine the associations between SHBG and total testosterone levels with diabetes by sex. To evaluate the impact of fatty liver, we used the fatty liver index (FLI), a validated measure derived from serum triglyceride levels, body mass index (BMI), waist circumference, and γ-glutamyltransferase levels.ResultsAfter adjusting for age, family history of diabetes, smoking, physical activity, BMI, and FLI, SHBG levels were inversely associated with diabetes among women (odds ratio [OR] comparing the highest with the lowest quartiles, 0.13 [95% confidence interval {CI}, 0.02–0.96]), but not among men. Similar patterns were observed in a subgroup analysis restricted to postmenopausal women"(OR, 0.12 [95% CI, 0.01–1.17]). In contrast, testosterone levels were inversely associated with diabetes among men (OR, 0.45 [95% CI, 0.23–0.89]), but not among women.ConclusionsOur findings suggest that SHBG in women and testosterone in men may be inversely associated with diabetes.
Highlights
Sex hormone-binding globulin (SHBG) levels and sex hormones have been implicated in the pathogenesis of type 2 diabetes and cardiovascular diseases
After multivariable adjustment for age, family history of diabetes, smoking, physical activity, and body mass index (BMI) (Table 3; Model 2), SHBG levels were inversely associated with diabetes among women (OR comparing the highest with the lowest quartiles, 0.13 [95% CI, 0.02–0.86]), but not among men (OR, 0.73 [95% CI, 0.38–1.40])
In a manner similar to total testosterone, after multivariable adjustment for known risk factors (Model 2), free testosterone levels were inversely associated with diabetes among men (OR, 0.44 [95% CI, 0.23–0.85]), but the estimates for women were very imprecise (OR, 15.28 [95% CI, 2.25–103.86])
Summary
Sex hormone-binding globulin (SHBG) levels and sex hormones have been implicated in the pathogenesis of type 2 diabetes and cardiovascular diseases. As fatty liver has been suggested to be a major determinant of SHBG levels, we examined whether the associations of SHBG and testosterone with diabetes were independent of fatty liver. Emerging data indicate that sex hormone-binding globulin (SHBG) as well as adipose tissue function may play important roles in the development of type 2 diabetes [1,2,3] and cardiovascular diseases [4,5]. SHBG is synthesized primarily in the liver and binds to androgens and Recent molecular epidemiologic studies mainly from Western populations have reported that genetically determined levels of SHBG were inversely associated with type 2 diabetes risk [2,9], lending support to the roles of SHBG in the development of type 2 diabetes. The previous studies examining the relation between SHBG and type 2 diabetes are mainly from European populations
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