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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BORIS DOI
Publisher DOI
PubMed ID
30256433
Description
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. This article is protected by copyright. All rights reserved.
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. This article is protected by copyright. All rights reserved.
Date of Publication
2019-01
Publication Type
Article
Subject(s)
600 - Technology::610 - Medicine & health
300 - Social sciences, sociology & anthropology::360 - Social problems & social services
Keyword(s)
Testosterone androgens diabetes hypogonadism metabolic diseases population health sex hormone-binding globulin
Language(s)
en
Contributor(s)
O'Reilly, Michael W | |
Glisic, Marija | |
Kumarendran, Balachandran | |
Subramanian, Anuradhaa | |
Manolopoulos, Konstantinos N | |
Tahrani, Abd A | |
Keerthy, Deepi | |
Muka, Taulant | |
Toulis, Konstantinos A | |
Hanif, Wasim | |
Thomas, G Neil | |
Arlt, Wiebke | |
Nirantharakumar, Krishnarajah |
Additional Credits
Institut für Sozial- und Präventivmedizin (ISPM)
Series
Clinical endocrinology
Publisher
Blackwell Scientific Publications
ISSN
0300-0664
Access(Rights)
open.access