Defy Medical

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, or 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 in the Cardiovascular Health Study free of diabetes and cardiovascular disease in 1994.

Main Outcome: Insulin resistance estimated by 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], 0.08–0.52; p=0.01) and total DHT (HOMA-IR 0.18 units lower per doubling; 95% CI 0.06–0.30; 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, 0.52–0.92; p=0.01), but SHBG (hazard ratio 1.09; 95% CI, 0.74–1.59; p=0.66) and free T (hazard ratio 1.15; 95% CI, 0.92–1.43; p=0.23) were not.

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

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (KEJ, KJM); Departments of Biostatistics (MLB), Psychiatry and Behavioral Sciences (MMS), and Medicine (AMM), University of Washington, Seattle, WA; Division on Aging, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (LD); Division of Nephrology-Hypertension, University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, CA (JHI); Departments of Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (JRK); New York Academy of Medicine, NY, New York (DSS); Geriatric Research, Education and Clinical Center (AMM), VA Puget Sound Health Care System (MMS, AMM), Seattle, WA Katherine E. Joyce, Mary L. Biggs, Luc Djoussé, Joachim H. Ix, Jorge R. Kizer, David S. Siscovick, Molly M. Shores, Alvin M. Matsumoto, and Kenneth J. Mukamal Address all correspondence and requests for reprints to: Kenneth J. Mukamal, MD, MPH, Beth Israel Deaconess Medical Center, 1309 Beacon Street, second Floor, Brookline, MA 02446

Received: July 08, 2016
Accepted: October 06, 2016
First Published Online: October 12, 2016
The Journal of Clinical Endocrinology & Metabolism