TY - JOUR
T1 - Testosterone, dihydrotestosterone, sex hormone-binding globulin, and incident diabetes among older men
T2 - The cardiovascular health study
AU - Joyce, Katherine E.
AU - Biggs, Mary L.
AU - Djoussé, Luc
AU - Ix, Joachim H.
AU - Kizer, Jorge R.
AU - Siscovick, David S.
AU - Shores, Molly M.
AU - Matsumoto, Alvin M.
AU - Mukamal, Kenneth J.
N1 - Publisher Copyright:
© 2017 by the Endocrine Society.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2016-2623
DO - 10.1210/jc.2016-2623
M3 - Article
C2 - 27732332
AN - SCOPUS:85010433120
SN - 0021-972X
VL - 102
SP - 33
EP - 39
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 1
ER -
