ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P190 | DOI: 10.1530/endoabs.65.P190

Androgen receptor reduced sensitivity is associated with increased mortality, poor glycemic control and BMI in men with type 2 diabetes - a 14-year follow up study

Adrian Heald1,2, Ghasem Yadegarfar3, Mark Livingston4, Helene Fachim1,2, Mark Lunt2, Ram Prakash Narayanan5, Kirk Siddals1,2, Gabriela Cortes6, Geoff Hackett7, Asma Naseem1, Rupinder Kochhar1, Khan Inamullah1, Rachelle Donn2, Martin Gibson1,2 & Hugh Jones8

1Salford Royal Hospital, Salford, UK; 2University of Manchester, Manchester, UK; 3Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran; 4Walsall Manor Hospital, Walsall, UK; 5University of Liverpool, Liverpool, UK; 6High Speciality Regional Hospital of Ixtapaluca, Mexico City, Mexico; 7Heartlands Hospital Birmingham, Birmingham, UK; 8University of Sheffield, Sheffield, United Kingtom

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 gene is associated with increased androgen receptor resistance/insulin resistance. We here investigated the link between CAG repeat number and outcomes in T2DM men.

Methods: We determined in a long-term 14-year follow-up cohort of 274 T2DM Caucasian men in Salford UK, the association between baseline androgen status/CAG repeat number and metabolic trajectory/mortality. Baseline serum total testosterone was determined by tandem mass spectrometry and CAG repeats by PCR followed by Sequenom sequencing.

Results: Lower baseline total testosterone was associated with higher Body Mass Index (BMI)(kg/m2) at 14-year follow-up: regression coefficient −0.30 (95% CI −0.445 to −0.157), P=0.0001 (total testosterone data). A higher baseline CAG repeat number associated with higher follow-up BMI in 2016 – each unit increase in CAG repeat associated with an increment of 0.43 in BMI 2016; and also higher HbA1c 2016. At an average 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 the number of CAG repeats and mortality such that 21-23 CAG repeats was associated with an up to 58% lower mortality rate than <21 CAG repeats and >23 CAG repeats. Thus there was an optimal number of CAG repeats in relation to mortality rate. This relation was independent of baseline testosterone.

Conclusion: A higher number of CAG repeats at the testosterone receptor gene is associated with a higher future BMI/increased HbA1c. There was a ‘u’ shaped relation between CAG repeat number and mortality rate. A greater understanding of the interaction between CAG repeat number and circulating testosterone level may aid understanding of longer term health outcomes in men with T2DM.