Testosterone, dihydrotestosterone, sex hormone-binding globulin, and incident diabetes among older men: The cardiovascular health study

Katherine E. Joyce, Mary L. Biggs, Luc Djoussé, Joachim H. Ix, Jorge Kizer, David S. Siscovick, Molly M. Shores, Alvin M. Matsumoto, Kenneth J. Mukamal

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)33-39
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume102
Issue number1
DOIs
StatePublished - Jan 1 2017

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Joyce, K. E., Biggs, M. L., Djoussé, L., Ix, J. H., Kizer, J., Siscovick, D. S., Shores, M. M., Matsumoto, A. M., & Mukamal, K. J. (2017). Testosterone, dihydrotestosterone, sex hormone-binding globulin, and incident diabetes among older men: The cardiovascular health study. Journal of Clinical Endocrinology and Metabolism, 102(1), 33-39. https://doi.org/10.1210/jc.2016-2623