PMID- 33634254 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220420 IS - 2574-0954 (Electronic) IS - 2574-0954 (Linking) VI - 10 IP - 1 DP - 2021 Mar TI - Androgen receptor-reduced sensitivity is associated with increased mortality and poorer glycaemia in men with type 2 diabetes mellitus: a prospective cohort study. PG - 37-44 LID - 10.1097/XCE.0000000000000230 [doi] AB - INTRODUCTION: Hypogonadism is associated with poorer glycaemic outcomes/increased all-cause and cardiovascular morbidity/mortality in type 2 diabetes mellitus (T2DM). Increasing CAG repeat number within exon-1 of the androgen receptor (AR) gene is associated with increased AR resistance/insulin resistance. METHODS: We determined in a long-term 14-year follow-up cohort of 423 T2DM Caucasian men, the association between baseline androgen status/CAG repeat number (by PCR then Sequenom sequencing) and metabolic/cardiovascular outcomes. RESULTS: Metabolic outcomes: Lower total testosterone was associated with higher BMI (kg/m(2)) at 14-year-follow-up: regression coefficient -0.30 (95% confidence interval -0.445 to -0.157), P = 0.0001. The range of CAG repeat number was 9-29 repeats. Higher CAG repeat number in exon-1 of the AR gene was associated with higher follow-up HbA1c2016 - each unit increase in CAG repeat-associated with an increment of 0.1% in HbA1C2016 (P = 0.04), independent of baseline testosterone. Cardiovascular outcomes and mortality: At an average of 14-year-follow-up, 55.8% of hypogonadal men had died vs 36.1% of eugonadal men (P = 0.001). There was a 'u' shaped relation between number of CAG repeats and mortality. Twenty-one CAG repeats were associated with an up to nearly 50% lower mortality rate than <21 CAG repeats and >21 CAG repeats - independent of baseline testosterone level. CONCLUSION: A higher number of CAG repeats at the AR gene associates with higher future HbA1c. There was a 'u' shaped relation between CAG repeat number and mortality rate. Determination of CAG repeat number may become part of assessment of androgen status/its consequences for men with T2DM. CI - Copyright (c) 2020 Wolters Kluwer Health, Inc. All rights reserved. FAU - Heald, Adrian H AU - Heald AH AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. AD - Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK. FAU - Yadegar Far, Ghasem AU - Yadegar Far G AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. AD - Heart Failure Research Centre & Epidemiology, Biostatics Department School of Public Heath, Isfahan University of Medical Sciences, Isfahan, Iran. FAU - Livingston, Mark AU - Livingston M AD - Department of Clinical Biochemistry, Black Country Pathology Services, Walsall Manor Hospital, Walsall. FAU - Fachim, Helene AU - Fachim H AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. AD - Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK. FAU - Lunt, Mark AU - Lunt M AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. FAU - Narayanan, Ram Prakash AU - Narayanan RP AD - Institute for Ageing and Chronic Diseases, University of Liverpool, Liverpool, UK. FAU - Siddals, Kirk AU - Siddals K AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. FAU - Moreno, Gabriela AU - Moreno G AD - General Directorate for Quality and Health Education, Mexico City, Mexico. FAU - Jones, Richard AU - Jones R AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. AD - Besins Healthcare, London. FAU - Malipatil, Nagaraj AU - Malipatil N AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. AD - Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK. FAU - Rutter, Martin AU - Rutter M AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. AD - Diabetes Centre Manchester University NHS Foundation Trust, Manchester. FAU - Gibson, Martin AU - Gibson M AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. AD - Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK. FAU - Donn, Rachelle AU - Donn R AD - Manchester Academic Health Sciences Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester. FAU - Hackett, Geoff AU - Hackett G AD - Department of Sexual Urology, Heartlands Hospital, Birmingham. FAU - Jones, Hugh AU - Jones H AD - Centre for Diabetes and Endocrinology, Barnsley Hospital, Barnsley. AD - Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK. LA - eng PT - Journal Article DEP - 20200818 PL - United States TA - Cardiovasc Endocrinol Metab JT - Cardiovascular endocrinology & metabolism JID - 101730894 PMC - PMC7901820 OTO - NOTNLM OT - BMI OT - androgen receptor OT - cardiovascular OT - mortality OT - testosterone OT - type 2 diabetes COIS- There are no conflicts of interest. EDAT- 2021/02/27 06:00 MHDA- 2021/02/27 06:01 PMCR- 2020/08/18 CRDT- 2021/02/26 06:05 PHST- 2020/06/21 00:00 [received] PHST- 2020/07/20 00:00 [accepted] PHST- 2021/02/26 06:05 [entrez] PHST- 2021/02/27 06:00 [pubmed] PHST- 2021/02/27 06:01 [medline] PHST- 2020/08/18 00:00 [pmc-release] AID - 10.1097/XCE.0000000000000230 [doi] PST - epublish SO - Cardiovasc Endocrinol Metab. 2020 Aug 18;10(1):37-44. doi: 10.1097/XCE.0000000000000230. eCollection 2021 Mar.