Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort

Michael O'reilly; Marija Glisic; Balachandran Kumarendran; Anuradhaa Subramanian; Konstantinos Manolopoulos; Abd Tahrani; Deepi Keerthy; Taulant  Muka; Konstantinos Toulis; Wasim Hanif; G Neil Thomas; Oscar H Franco; Wiebke Arlt; Krishnarajah Nirantharakumar

doi:10.1111/cen.13862

Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort

Michael O'reilly, Marija Glisic, Balachandran Kumarendran, Anuradhaa Subramanian, Konstantinos Manolopoulos, Abd Tahrani, Deepi Keerthy, Taulant Muka, Konstantinos Toulis, Wasim Hanif, G Neil Thomas, Oscar H Franco, Wiebke Arlt, Krishnarajah Nirantharakumar

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Abstract

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 ≥20nmol/l, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7nmol/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 1.5nmol/l, with the highest risk in women with serum testosterone ≥3.5nmol/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 <40nmol/L and <50nmol/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.

Key words: Testosterone, androgens, hypogonadism, sex hormone-binding globulin, diabetes, metabolic diseases, population health

Original language	English
Pages (from-to)	145-154
Number of pages	10
Journal	Clinical Endocrinology
Volume	90
Issue number	1
Early online date	26 Sept 2018
DOIs	https://doi.org/10.1111/cen.13862
Publication status	Published - Jan 2019

Bibliographical note

Keywords

Testosterone
androgens
hypogonadism
sex hormone-binding globulin
diabetes
metabolic diseases
population health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Michael_W_OʼReilly_Serum_testosterone_sex_hormone-binding_Clinical_Endocrinology_2018
Checked for eligibility: 25/09/2018 This is the accepted manuscript for a forthcoming publication in Clinical Endocrinology.
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O-Reilly_et_al_2018_Serum_testosterone_sex_hormone-binding_globulin_Clinical_EndocrinologyFinal published version, 530 KBLicence: Creative Commons: Attribution (CC BY)

Unravelling the Link Between Insulin Resistance and Androgen Excess (M. O'Reilly)
Arlt, W.
THE WELLCOME TRUST
1/08/12 → 31/07/15
Project: Research
The Role of DHEA Sulfation in the Pre-Receptor Regulation of Androgen Excess
Arlt, W.
THE WELLCOME TRUST
1/10/11 → 30/09/14
Project: Research

Cite this

O'reilly, M., Glisic, M., Kumarendran, B., Subramanian, A., Manolopoulos, K., Tahrani, A., Keerthy, D., Muka, T., Toulis, K., Hanif, W., Thomas, G. N., Franco, O. H., Arlt, W., & Nirantharakumar, K. (2019). Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort. Clinical Endocrinology, 90(1), 145-154. https://doi.org/10.1111/cen.13862

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title = "Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort",

abstract = "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 ≥20nmol/l, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7nmol/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 1.5nmol/l, with the highest risk in women with serum testosterone ≥3.5nmol/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 <40nmol/L and <50nmol/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. Key words: Testosterone, androgens, hypogonadism, sex hormone-binding globulin, diabetes, metabolic diseases, population health",

keywords = "Testosterone, androgens, hypogonadism, sex hormone-binding globulin, diabetes, metabolic diseases, population health",

author = "Michael O'reilly and Marija Glisic and Balachandran Kumarendran and Anuradhaa Subramanian and Konstantinos Manolopoulos and Abd Tahrani and Deepi Keerthy and Taulant Muka and Konstantinos Toulis and Wasim Hanif and Thomas, {G Neil} and Franco, {Oscar H} and Wiebke Arlt and Krishnarajah Nirantharakumar",

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O'reilly, M, Glisic, M, Kumarendran, B, Subramanian, A, Manolopoulos, K, Tahrani, A, Keerthy, D, Muka, T, Toulis, K, Hanif, W, Thomas, GN, Franco, OH, Arlt, W & Nirantharakumar, K 2019, 'Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort', Clinical Endocrinology, vol. 90, no. 1, pp. 145-154. https://doi.org/10.1111/cen.13862

TY - JOUR

T1 - Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort

AU - O'reilly, Michael

AU - Glisic, Marija

AU - Kumarendran, Balachandran

AU - Subramanian, Anuradhaa

AU - Manolopoulos, Konstantinos

AU - Tahrani, Abd

AU - Keerthy, Deepi

AU - Muka, Taulant

AU - Toulis, Konstantinos

AU - Hanif, Wasim

AU - Thomas, G Neil

AU - Franco, Oscar H

AU - Arlt, Wiebke

AU - Nirantharakumar, Krishnarajah

PY - 2019/1

Y1 - 2019/1

N2 - 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 ≥20nmol/l, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7nmol/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 1.5nmol/l, with the highest risk in women with serum testosterone ≥3.5nmol/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 <40nmol/L and <50nmol/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. Key words: Testosterone, androgens, hypogonadism, sex hormone-binding globulin, diabetes, metabolic diseases, population health

AB - 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 ≥20nmol/l, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7nmol/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 1.5nmol/l, with the highest risk in women with serum testosterone ≥3.5nmol/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 <40nmol/L and <50nmol/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. Key words: Testosterone, androgens, hypogonadism, sex hormone-binding globulin, diabetes, metabolic diseases, population health

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Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Projects

Unravelling the Link Between Insulin Resistance and Androgen Excess (M. O'Reilly)

The Role of DHEA Sulfation in the Pre-Receptor Regulation of Androgen Excess

Cite this