Testosterone and Sex Hormone–Binding Globulin Predict the Metabolic Syndrome and Diabetes in Middle-Aged Men
Abstract
OBJECTIVE—In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. We assessed the association of low levels of testosterone and sex hormone–binding globulin (SHBG) with the development of the metabolic syndrome and diabetes in men. RESEARCH DESIGN AND METHODS—Concentrations of SHBG and total and calculated free testosterone and factors related to insulin resistance were determined at baseline in 702 middle-aged Finnish men participating in a population-based cohort study. These men had neither diabetes nor the metabolic syndrome. RESULTS—After 11 years of follow-up, 147 men had developed the metabolic syndrome (National Cholesterol Education Program criteria) and 57 men diabetes. Men with total testosterone, calculated free testosterone, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome (odds ratio [OR] 2.3, 95% CI 1.5–3.4; 1.7, 1.2–2.5; and 2.8, 1.9–4.1, respectively) and diabetes (2.3, 1.3–4.1; 1.7, 0.9–3.0; and 4.3, 2.4–7.7, respectively) after adjustment for age. Adjustment for potential confounders such as cardiovascular disease, smoking, alcohol intake, and socioeconomic status did not alter the associations. Factors related to insulin resistance attenuated the associations, but they remained significant, except for free testosterone. CONCLUSIONS—Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men. Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis.
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Because of high prevalence of cooccurrence of T2D and obesity, low T was also associated with metabolic syndrome.
“Furthermore, because of high prevalence of cooccurrence of T2D and obesity, low T was unsurprisingly also associated with metabolic syndrome [171, 172].”
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 [172]
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- Authors
- Laaksonen, D. E., Niskanen, L., Punnonen, K., Nyyssönen, K., Tuomainen, T.-P., Valkonen, V.-P., Salonen, R., & Salonen, J. T.
- Affiliations
- University of Eastern Finland (FI)
- Kuopio University Hospital (FI)
- Research Institute of Public Health, University of Kuopio, Kuopio, Finland
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2004-05-01
- Volume
- 27
- Issue
- 5
- Pages
- 1036-1041
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2165913105
- Cited by
- 920
- References
- 10
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 22 · 2023: 27 · 2022: 31 · 2021: 31 · 2020: 23 · 2019: 27 · 2018: 42 · 2017: 50 · 2016: 36 · 2015: 53 · 2014: 57 · 2013: 61 · 2012: 71
- FWCI
- 20.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-44199, R01HL044199)
- 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
- testosterone, sex hormone-binding globulin, metabolic syndrome, diabetes mellitus, hypoandrogenism, free testosterone, insulin resistance, middle-aged men, risk prediction, glucose metabolism
- MeSH terms
- Diabetes Mellitus, Type 2, Follow-Up Studies, Humans, Insulin Resistance, Male, Middle Aged, Predictive Value of Tests, Risk Factors, Sex Hormone-Binding Globulin, Smoking, Testosterone, Body Mass Index, Odds Ratio, Metabolic Syndrome
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