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J Clin Endocrinol Metab. 2017 Jan 1;102(1):33-39. doi: 10.1210/jc.2016-2623.

Testosterone, Dihydrotestosterone, Sex Hormone-Binding Globulin, and Incident Diabetes Among Older Men: The Cardiovascular Health Study.

Author information

1
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215.
2
Departments of Biostatistics.
3
Division on Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
4
Division of Nephrology-Hypertension, University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California 92093.
5
Departments of Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461.
6
New York Academy of Medicine, New York, New York 10029; and.
7
Psychiatry and Behavioral Sciences, and.
8
VA Puget Sound Health Care System, Seattle, Washington 98108.
9
Medicine, University of Washington, Seattle, Washington 98115.
10
Geriatric Research, Education and Clinical Center.

Abstract

Context:

Although sex hormone-binding globulin (SHBG) and testosterone (T) have been inversely associated with risk of diabetes, few studies have examined dihydrotestosterone (DHT), a more potent androgen than T, in older adults, whose glycemic pathophysiology differs from younger adults.

Objective:

To determine the associations of SHBG, T, and DHT with insulin resistance and incident diabetes in older adult men.

Design:

In a prospective cohort study, we evaluated baseline levels of SHBG, T, and DHT using liquid chromatography-tandem mass spectrometry among 852 men free of diabetes and cardiovascular disease in the Cardiovascular Health Study in 1994.

Main Outcome:

Insulin resistance estimated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and insulin sensitivity estimated by the Gutt index in 1996, and incident diabetes (n = 112) ascertained over a mean follow-up of 9.8 years.

Results:

In linear regression models adjusted for demographics, alcohol consumption, current smoking, body mass index, and other androgens, SHBG [HOMA-IR 0.30 units lower per doubling; 95% confidence interval (CI), 0.08 to 0.52; P = 0.01] and total DHT (HOMA-IR 0.18 units lower per doubling; 95% CI, 0.06 to 0.30; P = 0.01), but not free T (P = 0.33), were inversely associated with insulin resistance. In corresponding Cox proportional hazards models, total DHT was again inversely associated with risk of diabetes (adjusted hazard ratio per doubling, 0.69; 95% CI, 0.52 to 0.92; P = 0.01), but SHBG (hazard ratio, 1.09; 95% CI, 0.74 to 1.59; P = 0.66) and free T (hazard ratio, 1.15; 95% CI, 0.92 to 1.43; P = 0.23) were not.

Conclusions:

Among older men, higher levels of DHT were inversely associated with insulin resistance and risk of diabetes over the ensuing 10 years, whereas levels of T were not. Future studies are still needed to clarify the role of SHBG in risk of diabetes in this population.

PMID:
27732332
PMCID:
PMC5413109
DOI:
10.1210/jc.2016-2623
[Indexed for MEDLINE]
Free PMC Article

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