Steroid Sex Hormones, Sex Hormone-Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program.

J Clin Endocrinol Metab
Authors
Keywords
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.

Year of Publication
2015
Journal
J Clin Endocrinol Metab
Volume
100
Issue
10
Pages
3778-86
Date Published
2015 Oct
ISSN
1945-7197
URL
DOI
10.1210/jc.2015-2328
PubMed ID
26200237
PubMed Central ID
PMC4596040
Links
Grant list
U01 DK048437 / DK / NIDDK NIH HHS / United States
U01 DK048406 / DK / NIDDK NIH HHS / United States
U01 DK048407 / DK / NIDDK NIH HHS / United States
U01 DK048412 / DK / NIDDK NIH HHS / United States
U01 DK048375 / DK / NIDDK NIH HHS / United States
U01 DK048434 / DK / NIDDK NIH HHS / United States
U01 DK048413 / DK / NIDDK NIH HHS / United States
R01 DK072041 / DK / NIDDK NIH HHS / United States
UL1 TR001409 / TR / NCATS NIH HHS / United States
U01 DK048397 / DK / NIDDK NIH HHS / United States
U01 DK048381 / DK / NIDDK NIH HHS / United States
U01 DK048339 / DK / NIDDK NIH HHS / United States
U01 DK048514 / DK / NIDDK NIH HHS / United States
U01 DK048485 / DK / NIDDK NIH HHS / United States
U01 DK048411 / DK / NIDDK NIH HHS / United States
U01 DK048443 / DK / NIDDK NIH HHS / United States
U01 DK048380 / DK / NIDDK NIH HHS / United States
U01 DK048400 / DK / NIDDK NIH HHS / United States
U01 DK048468 / DK / NIDDK NIH HHS / United States
U01 DK048387 / DK / NIDDK NIH HHS / United States
U01 DK048404 / DK / NIDDK NIH HHS / United States
U01 DK048489 / DK / NIDDK NIH HHS / United States
U01 DK048349 / DK / NIDDK NIH HHS / United States
U01 DK048377 / DK / NIDDK NIH HHS / United States
P30 DK017047 / DK / NIDDK NIH HHS / United States