Coffee and Caffeine Consumption in Relation to Sex Hormone-Binding Globulin and Risk of Type 2 Diabetes in Postmenopausal Women

OBJECTIVE-Coffee consumption has been inversely associated with type 2 diabetes risk, but its mechanisms are largely unknown. We aimed to examine whether plasma levels of sex hormones and sex hormone-binding globulin (SHBG) may account for the inverse association between coffee consumption and type 2 diabetes risk. RESEARCH DESIGN AND METHODS-We conducted a case-control study nested in the prospective Women's Health Study (WHS). During a median follow-up of 10 years, 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age, race, duration of follow-up, and time of blood draw. RESULTS-Caffeinated coffee was positively associated with SHBG but not with sex hormones. Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming >= 4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers (P for trend = 0.01). In contrast, neither decaffeinated coffee nor tea was associated with SHBG or sex hormones. The multivariable-adjusted odds ratio (OR) of type 2 diabetes for women consuming >= 4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 (95% CI 0.23-0.94; P for trend = 0.047). The association was largely attenuated after further adjusting for SHBG (OR 0.71 [95% CI 0.31-1.61]; P for trend = 0.47). In addition, carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming >= 2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG. CONCLUSIONS-Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women. Diabetes 60: 269-275, 2011