Testosterone, Dihydrotestosterone, Sex Hormone Binding Globulin and Incident Diabetes among Older Men: the Cardiovascular Health Study
Open accessAbstract
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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The association between SHBG and T2D holds after adjusting for BMI and other common risk factors, implying lower SHBG as a predictor for T2D is at least partially independent of BMI.
“Importantly, the association between SHBG and T2D also holds after adjusting for BMI and other common risk factors, implying lower SHBG as a predictor for T2D is at least partially independent of BMI [118, 121, 124].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [124]
The Results (Table 2) show no significant association between SHBG and incident diabetes after adjustment for BMI and other risk factors (hazard ratio 0.88, 95% CI 0.62–1.24). The Discussion likewise states that SHBG was not significantly related to diabetes risk in this cohort of older men. The paper does report an association between SHBG and insulin resistance, but that is a different outcome. (LLM, conf=0.90)
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- Authors
- Joyce, K. E., Biggs, M. L., Djoussé, L., Ix, J. H., Kizer, J. R., Siscovick, D. S., Shores, M. M., Matsumoto, A. M., & Mukamal, K. J.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Brigham and Women's Hospital (US)
- University of California San Diego (US)
- Albert Einstein College of Medicine (US)
- New York Academy of Medicine (US)
- VA Puget Sound Health Care System (US)
- University of Washington (US)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-10-12
- Volume
- 102
- Issue
- 1
- Pages
- jc.2016-2623
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5413109
- OpenAlex
- W2530281554
- Cited by
- 40
- References
- 8
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 8
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc085079-024, n01hc085083-027, n01hc085080-026, n01hc085086-022, n01hc55222-0-0-0)
- National Institute on Aging (R01AG023629)
- National Heart, Lung, and Blood Institute (N01 HC085086, N01 HC085079, R01HL094555, N01 HC085083, R01HL091952, N01 HC085080, HHSN 268200800007C, HHSN268201200036C, N01HC085082, U01HL080295, N01 HC055222, N01 HC085081)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020541)
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- testosterone, dihydrotestosterone, sex hormone-binding globulin, insulin resistance, new-onset diabetes, older men, androgens, HOMA-IR, insulin sensitivity, free testosterone, Cardiovascular Health Study, sex differences in diabetes risk
- MeSH terms
- Adult, Aged, Cardiovascular Diseases, Diabetes Mellitus, Follow-Up Studies, Humans, Insulin Resistance, Longitudinal Studies, Male, Middle Aged, Prognosis, Prospective Studies, Sex Hormone-Binding Globulin, Dihydrotestosterone, Testosterone, Biomarkers, Incidence
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