O'Reilly, Michael WMichael WO'ReillyGlisic, MarijaMarijaGlisicKumarendran, BalachandranBalachandranKumarendranSubramanian, AnuradhaaAnuradhaaSubramanianManolopoulos, Konstantinos NKonstantinos NManolopoulosTahrani, Abd AAbd ATahraniKeerthy, DeepiDeepiKeerthyMuka, TaulantTaulantMukaToulis, Konstantinos AKonstantinos AToulisHanif, WasimWasimHanifThomas, G NeilG NeilThomasFranco Duran, Oscar HoracioOscar HoracioFranco DuranArlt, WiebkeWiebkeArltNirantharakumar, KrishnarajahKrishnarajahNirantharakumar2024-10-072024-10-072019-01https://boris-portal.unibe.ch/handle/20.500.12422/59997OBJECTIVE 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.enTestosterone androgens diabetes hypogonadism metabolic diseases population health sex hormone-binding globulin600 - Technology::610 - Medicine & health300 - Social sciences, sociology & anthropology::360 - Social problems & social servicesarticle10.7892/boris.1203233025643310.1111/cen.13862