Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort
Author(s)
O'Reilly, Michael W
Glisic, Marija
Kumarendran, Balachandran
Subramanian, Anuradhaa
Manolopoulos, Konstantinos N
Type
Journal Article
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 ≥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.
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.
Date Issued
2019-01-01
Date Acceptance
2018-09-21
Citation
Clinical Endocrinology, 2019, 90 (1), pp.145-154
ISSN
0300-0664
Publisher
Wiley
Start Page
145
End Page
154
Journal / Book Title
Clinical Endocrinology
Volume
90
Issue
1
Copyright Statement
© 2018 The Authors Clinical Endocrinology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30256433
Subjects
ALL-CAUSE MORTALITY
ANDROGEN-DEPRIVATION THERAPY
androgens
ASSOCIATION
diabetes
Endocrinology & Metabolism
GLUCOSE-TOLERANCE
hypogonadism
HYPOGONADISM
Life Sciences & Biomedicine
metabolic diseases
METABOLIC SYNDROME
OLDER MEN
POLYCYSTIC-OVARY-SYNDROME
POPULATION
population health
Science & Technology
sex hormone-binding globulin
testosterone
WOMEN
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2018-12-18