PMID- 30256433 OWN - NLM STAT- MEDLINE DCOM- 20200317 LR - 20240214 IS - 1365-2265 (Electronic) IS - 0300-0664 (Print) IS - 0300-0664 (Linking) VI - 90 IP - 1 DP - 2019 Jan TI - Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort. PG - 145-154 LID - 10.1111/cen.13862 [doi] 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 >/=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. CI - (c) 2018 The Authors Clinical Endocrinology Published by John Wiley & Sons Ltd. FAU - O'Reilly, Michael W AU - O'Reilly MW AUID- ORCID: 0000-0002-9108-9105 AD - Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. AD - Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. FAU - Glisic, Marija AU - Glisic M AD - Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands. FAU - Kumarendran, Balachandran AU - Kumarendran B AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. AD - Department of Public Health, Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka. FAU - Subramanian, Anuradhaa AU - Subramanian A AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. FAU - Manolopoulos, Konstantinos N AU - Manolopoulos KN AD - Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. AD - Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. FAU - Tahrani, Abd A AU - Tahrani AA AD - Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. AD - Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. FAU - Keerthy, Deepi AU - Keerthy D AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. FAU - Muka, Taulant AU - Muka T AD - Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands. FAU - Toulis, Konstantinos A AU - Toulis KA AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. FAU - Hanif, Wasim AU - Hanif W AD - Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. FAU - Thomas, G Neil AU - Thomas GN AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. FAU - Franco, Oscar H AU - Franco OH AD - Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands. AD - Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. FAU - Arlt, Wiebke AU - Arlt W AD - Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. AD - Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. FAU - Nirantharakumar, Krishnarajah AU - Nirantharakumar K AD - Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. LA - eng GR - CS-2013-13-029/DH_/Department of Health/United Kingdom GR - 099909/WT_/Wellcome Trust/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - 209492/Z/17/Z/WT_/Wellcome Trust/United Kingdom GR - MC_PC_15079/MRC_/Medical Research Council/United Kingdom GR - MR/S003878/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181023 PL - England TA - Clin Endocrinol (Oxf) JT - Clinical endocrinology JID - 0346653 RN - 0 (Androgens) RN - 0 (Sex Hormone-Binding Globulin) RN - 3XMK78S47O (Testosterone) SB - IM MH - Adult MH - Aged MH - Androgens/deficiency MH - Cohort Studies MH - Diabetes Mellitus, Type 2/blood/*etiology MH - Female MH - Humans MH - Longitudinal Studies MH - Male MH - Middle Aged MH - Primary Health Care MH - Retrospective Studies MH - Risk Factors MH - *Sex Factors MH - Sex Hormone-Binding Globulin/*analysis MH - Testosterone/*blood MH - Young Adult PMC - PMC6334272 OTO - NOTNLM OT - androgens OT - diabetes OT - hypogonadism OT - metabolic diseases OT - population health OT - sex hormone-binding globulin OT - testosterone EDAT- 2018/09/27 06:00 MHDA- 2020/03/18 06:00 PMCR- 2019/01/16 CRDT- 2018/09/27 06:00 PHST- 2018/06/21 00:00 [received] PHST- 2018/08/24 00:00 [revised] PHST- 2018/09/21 00:00 [accepted] PHST- 2018/09/27 06:00 [pubmed] PHST- 2020/03/18 06:00 [medline] PHST- 2018/09/27 06:00 [entrez] PHST- 2019/01/16 00:00 [pmc-release] AID - CEN13862 [pii] AID - 10.1111/cen.13862 [doi] PST - ppublish SO - Clin Endocrinol (Oxf). 2019 Jan;90(1):145-154. doi: 10.1111/cen.13862. Epub 2018 Oct 23.