SFEBES2019 POSTER PRESENTATIONS Metabolism and Obesity (104 abstracts)
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 Heald 1, , Ghasem Yadegarfar 3 , Mark Livingston 4 , Helene Fachim 1, , Mark Lunt 2 , Ram Prakash Narayanan 5 , Kirk Siddals 1, , Gabriela Cortes 6 , Geoff Hackett 7 , Asma Naseem 1 , Rupinder Kochhar 1 , Khan Inamullah 1 , Rachelle Donn 2 , Martin Gibson 1, & Hugh Jones 8
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.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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