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Cited by 307Hormonal and reproductive studiesDiabetes, Cardiovascular Risks, and LipoproteinsSperm and Testicular Function

Association of Bioavailable, Free, and Total Testosterone With Insulin Resistance

Tsai, Elaine C., Matsumoto, Alvin M., Fujimoto, Wilfred Y., Boyko, Edward J.·2004·Diabetes Care
DOI 10.2337/diacare.27.4.861
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Abstract

OBJECTIVE: Previous reports of an association between low testosterone levels and diabetes risk were often confounded by covariation of sex hormone-binding globulin (SHBG) and testosterone measurements. Measurements of bioavailable and free testosterone, more reliable indexes of biologically active testosterone, were examined for their associations with markers of insulin resistance and body fat measures in 221 middle-aged nondiabetic men. RESEARCH DESIGN AND METHODS: Bioavailable and free testosterone were calculated from the concentrations of total testosterone, SHBG, and albumin, and they were not significantly correlated with SHBG (r = 0.07-0.1). In contrast, total testosterone correlated significantly with SHBG (r = 0.63). We evaluated the relationship between these measures of circulating testosterone and markers for insulin resistance (i.e., fasting insulin, C-peptide, and homeostasis model assessment for insulin resistance [HOMA-IR]) as well as total body fat (assessed by dual-energy X-ray absorptiometry [DEXA]) and abdominal fat distribution (assessed by single-slice computed tomography [CT]). RESULTS: Bioavailable, free, and total testosterone and SHBG all correlated significantly with fasting insulin (age-adjusted r = -0.15 [P = 0.03], -0.14 [P = 0.03], -0.32 [P < 0.0001], and -0.38 [P < 0.0001], respectively), fasting C-peptide (r = -0.18 [P = 0.009] to -0.41 [P < 0.0001]), HOMA-IR (r = -0.15 [P = 0.03] to - 0.39 [P < 0.0001]), and body fat measures (r = -0.17 [P = 0.008] to -0.44 [P < 0.0001]). Only SHBG and total testosterone were significantly associated with fasting glucose (r = -0.20 [P = 0.003] to -0.21 [P = 0.002]). In multivariate analysis, bioavailable or free testosterone was significantly and inversely associated with insulin, C-peptide, and HOMA-IR, but this was not independent of total body or abdominal fat. SHBG was a significant determinant of insulin, C-peptide, and HOMA-IR, independent of body fat. The associations between total testosterone and insulin resistance were confounded by SHBG. CONCLUSIONS: The inverse association between testosterone and insulin resistance, independent of SHBG, was mediated through body fat.

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Authors
Tsai, E. C., Matsumoto, A. M., Fujimoto, W. Y., & Boyko, E. J.
Affiliations
University of Washington (US)
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2004-04-01
Volume
27
Issue
4
Pages
861-868
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/diacare.27.4.861
OpenAlex
W1995508866
Cited by
307
References
39
Citations by year
2026: 6 · 2025: 5 · 2024: 11 · 2023: 12 · 2022: 16 · 2021: 10 · 2020: 13 · 2019: 13 · 2018: 16 · 2017: 16 · 2016: 8 · 2015: 19 · 2014: 20 · 2013: 11 · 2012: 14
FWCI
7.85
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
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, bioavailable testosterone, free testosterone, total testosterone, sex hormone-binding globulin, insulin resistance, HOMA-IR, C-peptide, fasting insulin, fat mass, abdominal fat, diabetes risk, middle-aged men, sex hormones, insulin sensitivity, glucose metabolism, aging, sex differences in aging, sex differences in obesity
MeSH terms
Adipose Tissue, Biological Availability, Blood Glucose, Cross-Sectional Studies, Fasting, Humans, Insulin, Insulin Resistance, Longitudinal Studies, Male, Middle Aged, Sex Hormone-Binding Globulin, Testosterone, Cohort Studies, Multivariate Analysis

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