Sex Hormone-Binding Globulin as an Independent Predictor of Incident Type 2 Diabetes Mellitus in Men

Lakshman, K. M.; Bhasin, S.; Araujo, A. B.

doi:10.1093/gerona/glq002

Cited by 100Hormonal and reproductive studiesDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

Sex Hormone-Binding Globulin as an Independent Predictor of Incident Type 2 Diabetes Mellitus in Men

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Lakshman, K. M., Bhasin, S., Araujo, A. B.·2010·The Journals of Gerontology Series A: Biological Sciences and Medical Sciences

DOI 10.1093/gerona/glq002PMC PMC2854882

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Abstract

BACKGROUND: Low levels of sex hormone-binding globulin (SHBG) and total testosterone (T) in men have been associated with increased risk of type 2 diabetes mellitus (T2DM). As total T and SHBG levels are highly correlated, we determined whether SHBG influences the risk of T2DM through T or whether SHBG is an independent predictor of T2DM. METHODS: Longitudinal analyses were conducted on men participating in the Massachusetts Male Aging Study, a population-based study of men aged 40-70 years. Of 1,709 men enrolled in 1987-1989, 1,156 were evaluated 7-10 years later and 853 after 15-17 years. Analyses were restricted to 1,128 men without T2DM at baseline. RESULTS: Ninety new cases of T2DM were identified. After adjustment for age, body mass index, hypertension, smoking, alcohol intake, and physical activity, the hazard ratio (HR) for incident T2DM was 2.0 for each 1 SD decrease in SHBG (95% confidence interval [CI], 1.42-2.82, p < .001) and 1.29 for each 1 SD decrease in total T (95% CI, 1.01-1.66, p = .04). Free T was not associated with T2DM (HR = 1.03, 95% CI, 0.81-1.31, p = .79). The strong association of T2DM risk with SHBG persisted even after additional adjustment for free T (HR = 2.04, 95% CI, 1.44-2.87, p < .0001) or total T (HR = 1.95, 95% CI, 1.34-2.82, p = .0004). CONCLUSIONS: SHBG is an independent predictor of incident T2DM even after adjusting for free T or total T. Free T is not significantly associated with T2DM. SHBG may contribute to the risk of T2DM through nonandrogenic mechanisms, which should be investigated as they may provide novel targets for diabetes prevention.

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The same inverse association between SHBG and T2D has been confirmed in multiple other studies in both men and women.
“The same inverse association between SHBG and T2D has been confirmed in multiple other studies in both men and women [120–123].”
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 [122]
The Results and Discussion report an inverse association between SHBG and incident T2D in men and note similar findings in previous studies. This study enrolled only men; although it cites a study of women and men, it does not itself confirm the association in women or establish that multiple studies did so. (LLM, conf=0.85)
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Hu, J.-B., Zhang, A., Yang, S.-M., Wang, Y., Goswami, R., Zhou, H., Zhang, Y., Wang, Z.-H., Li, R., Cheng, Q.-F., et al. (2016) · Journal of Diabetes · doi:10.1111/1753-0407.12322 · Cited by 42 · see citing works
485Prospective associations between sex hormone-binding globulin and risk of type 2 diabetes
Woo, H. W., Shin, M., Choi, B. Y., & Kim, M. K. (2021) · International Journal of Epidemiology · doi:10.1093/ije/dyab168.718
Sex hormone-binding globulin, genetic susceptibility, and the risk of type 2 diabetes in men and postmenopausal women
Zhang, W., Zhang, H., Wang, B., Wang, Y., Wang, N., & Lu, Y. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002791 · Cited by 2 · see citing works

Authors: Lakshman, K. M., Bhasin, S., & Araujo, A. B.
Affiliations: New England Research Institutes (US)
Boston University (US)
ORCID: Bhasin, S.
Venue: The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Publisher: Oxford University Press (OUP)
Published: 2010-01-27
Volume: 65A
Issue: 5
Pages: 503-509
ISSN: 1079-5006 (ISSN-L)
1758-535X
DOI: 10.1093/gerona/glq002
PMC: PMC2854882
OpenAlex: W2114817259
Cited by: 100
References: 54
Citations by year: 2026: 2 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 8 · 2019: 2 · 2018: 7 · 2017: 9 · 2016: 4 · 2015: 7 · 2014: 8 · 2013: 9 · 2012: 6
FWCI: 8.23
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journals of Gerontology Series A (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p30ag031679-15)
National Institute on Aging (5 P30 AG031679, R01AG04673, 1R01AG22356)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK044995, R01DK44995, R01DK51345, R01DK051345)
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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: sex hormone-binding globulin, type 2 diabetes, incident diabetes risk, men, total testosterone, free testosterone, diabetes prevention, Massachusetts Male Aging Study
MeSH terms: Adult, Age Factors, Aged, Aging, Diabetes Mellitus, Type 2, Humans, Longitudinal Studies, Male, Middle Aged, Regression Analysis, Risk Factors, Sex Hormone-Binding Globulin, Testosterone, Body Mass Index, Proportional Hazards Models

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Sex Hormone-Binding Globulin as an Independent Predictor of Incident Type 2 Diabetes Mellitus in Men

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