Citation: Journal of Clinical Endocrinology & Metabolism. 100(10):3778-86, 2015 Oct..Journal: The Journal of clinical endocrinology and metabolism.ISSN: 0021-972X.Full author list: Mather KJ; Kim C; Christophi CA; Aroda VR; Knowler WC; Edelstein SE; Florez JC; Labrie F; Kahn SE; Goldberg RB; Barrett-Connor E; Diabetes Prevention Program.UI/PMID: 26200237.Subject(s): Adult | Aged | *Androgens/bl [Blood] | Blood Glucose/an [Analysis] | Body Mass Index | *Diabetes Mellitus, Type 2/bl [Blood] | *Diabetes Mellitus, Type 2/ep [Epidemiology] | Diabetes Mellitus, Type 2/pc [Prevention & Control] | *Estrogens/bl [Blood] | Female | Humans | Incidence | Male | Middle Aged | Polymorphism, Single Nucleotide | Risk Factors | Sex Hormone-Binding Globulin/ge [Genetics] | *Sex Hormone-Binding Globulin/me [Metabolism] | United States | Waist CircumferenceInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal Article | Multicenter Study | Randomized Controlled Trial | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.SDigital Object Identifier: http://dx.doi.org/10.1210/jc.2015-2328 (Click here)Abbreviated citation: J Clin Endocrinol Metab. 100(10):3778-86, 2015 Oct.Local Holdings: Available online through MWHC library: 1999- June 2013, Available in print through MWHC library: 1999 - 2006.Abstract: CONTEXT: Steroid sex hormones and SHBG may modify metabolism and diabetes risk, with implications for sex-specific diabetes risk and effects of prevention interventions; OBJECTIVE: This study aimed to evaluate the relationships of steroid sex hormones, SHBG and SHBG single-nucleotide polymorphisms (SNPs) with diabetes risk factors and with progression to diabetes in the Diabetes Prevention Program (DPP); DESIGN AND SETTING: This was a secondary analysis of a multicenter randomized clinical trial involving 27 U.S. academic institutions; PARTICIPANTS: The study included 2898 DPP participants: 969 men, 948 premenopausal women not taking exogenous sex hormones, 550 postmenopausal women not taking exogenous sex hormones, and 431 postmenopausal women taking exogenous sex hormones; INTERVENTIONS: Participants were randomized to receive intensive lifestyle intervention, metformin, or placebo; MAIN OUTCOMES: Associations of steroid sex hormones, SHBG, and SHBG SNPs with glycemia and diabetes risk factors, and with incident diabetes over median 3.0 years (maximum, 5.0 y); RESULTS: T and DHT were inversely associated with fasting glucose in men, and estrone sulfate was directly associated with 2-hour post-challenge glucose in men and premenopausal women. SHBG was associated with fasting glucose in premenopausal women not taking exogenous sex hormones, and in postmenopausal women taking exogenous sex hormones, but not in the other groups. Diabetes incidence was directly associated with estrone and estradiol and inversely with T in men; the association with T was lost after adjustment for waist circumference. Sex steroids were not associated with diabetes outcomes in women. SHBG and SHBG SNPs did not predict incident diabetes in the DPP population; CONCLUSIONS: Estrogens and T predicted diabetes risk in men but not in women. SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones.