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

MW O'Reilly, M Glisic, B Kumarendran… - Clinical …, 2019 - Wiley Online Library
Clinical endocrinology, 2019Wiley Online Library
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 …
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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