Serum testosterone, sex hormone‐binding globulin and sex‐specific risk of incident type 2 diabetes in a retrospective primary care cohort
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Summary: Objective: Previous studies suggest that androgens have a sexually dimorphic impact on metabolic dysfunction. However, the sex‐specific link between circulating androgens and risk of type 2 diabetes mellitus (T2DM) has not been examined in a large scale, longitudinal cohort, a task we undertook in this study. Design: A retrospective cohort study in a UK primary care database. Patients: We included men and women with available serum testosterone and sex hormone‐binding globulin (SHBG) results. Measurements: We categorized serum concentrations according to clinically relevant cut‐off points and calculated crude and adjusted T2DM Incidence Rate Ratios (IRRs and aIRRs). Results: Serum testosterone concentrations were available in 70 541 men and 81 889 women; serum SHBG was available in 15 907 men and 42 034 women. In comparison to a reference cohort with serum testosterone ≥20 nmol/L, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7 nmol/L (aIRR 2.71, 95% CI 2.34‐3.14, P < 0.001). In women, the risk of T2DM started to increase significantly when serum testosterone concentrations exceeded 1.5 nmol/L, with the highest risk in women with serum testosterone ≥3.5 nmol/L (aIRR 1.98, 95% CI 1.55‐2.52, P < 0.001). These observations were verified in a continuous rather than categorized analysis. The risk of T2DM increased in men and women with serum SHBG <40 and <50 nmol/L, respectively. Conclusions/Interpretation: In this longitudinal study, we found sexually dimorphic associations between serum testosterone and risk of incident T2DM. Androgen deficiency and excess should be considered important risk factors for diabetes in men and women, respectively.
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Lower SHBG was an independent risk factor for the development of T2D, inferring a five- or ninefold higher risk for male and female subjects, respectively, as compared to the reference group.
“In a large longitudinal cohort study, lower SHBG was an independent risk factor for the development of T2D, inferring a five- or ninefold higher risk for male and female subjects, respectively, as compared to the reference group, hereby confirming findings from smaller studies [117–119].”
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 [117]
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- Authors
- O’Reilly, M. W., Glisic, M., Kumarendran, B., Subramanian, A., Manolopoulos, K. N., Tahrani, A. A., Keerthy, D., Muka, T., Toulis, K. A., Hanif, W., Thomas, G. N., Franco, O. H., Arlt, W., & Nirantharakumar, K.
- Affiliations
- University of Birmingham (GB)
- Department of Epidemiology Erasmus University Medical Centre Rotterdam The Netherlands
- University of Kelaniya (LK)
- Institute of Applied Health Research University of Birmingham Birmingham UK
- Erasmus MC (NL)
- Centre for Endocrinology, Diabetes and Metabolism Birmingham Health Partners Birmingham UK
- University of Bern (CH)
- Corresponding author
- Nirantharakumar, Krishnarajah
- ORCID
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2018-10-23
- Volume
- 90
- Issue
- 1
- Pages
- 145-154
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- PMC
- PMC6334272
- OpenAlex
- W2892543413
- Cited by
- 72
- References
- 46
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 14 · 2023: 8 · 2022: 7 · 2021: 9 · 2020: 9 · 2019: 6 · 2018: 2 · 2017: 1
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- BORIS (University Library Bern) (submittedVersion, other-oa)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Open Access CRIS of the University of Bern
- Funders
- Wellcome Trust (209492/Z/17/Z)
- National Institute on Handicapped Research
- 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 › Ovarian function and disorders
- Keywords
- type 2 diabetes, testosterone, sex hormone-binding globulin, androgens, sex differences, androgen deficiency, hyperandrogenism, diabetes risk, primary care cohort
- MeSH terms
- Adult, Aged, Androgens, Diabetes Mellitus, Type 2, Female, Humans, Longitudinal Studies, Male, Middle Aged, Primary Health Care, Retrospective Studies, Risk Factors, Sex Factors, Sex Hormone-Binding Globulin, Testosterone, Cohort Studies, Young Adult
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