P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study

Adrian Heald; Ghasem Yadegarfar; Mark Livingston; Helene Fachim; Ram Prakash Narayanan; Mark Lunt; Kirk Siddals; Gabriela Cortes; Martin Gibson; Rachelle Donn; Simon Anderson; Geoff Hackett; Hugh Jones

doi:10.2991/artres.k.191224.163

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Volume 25, Issue Supplement 1, December 2019, Pages S178 - S179

P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study

Authors

Adrian Heald¹^{, 2}^{, *}, Ghasem Yadegarfar²^{, 3}, Mark Livingston⁴, Helene Fachim¹^{, 2}, Ram Prakash Narayanan²^{, 5}, Mark Lunt⁶, Kirk Siddals⁶, Gabriela Cortes⁷, Martin Gibson¹^{, 2}, Rachelle Donn², Simon Anderson⁸, Geoff Hackett⁹, Hugh Jones¹⁰

¹Salford Royal Hospital, Salford, UK

²University of Manchester, UK

³Isfahan University of Medical Sciences, Isfahan, Iran

⁴Walsall Manor Hospital, Walsall, UK

⁵University of Liverpool, UK

⁶University of Manchester

⁷High Speciality Regional Hospital of Ixtapaluca, Mexico City, Mexico

⁸University of the West Indies, Barbados

⁹Heartlands Hospital, Birmingham, UK

¹⁰University of Sheffield, Sheffield, UK

^*Corresponding author. Email: adrian.heald@manchester.ac.uk

Corresponding Author

Adrian Heald

Available Online 17 February 2020.

DOI

10.2991/artres.k.191224.163 How to use a DOI?

Abstract

Background: Hypogonadism associates with increased cardiovascular morbidity/mortality in type 2 diabetes mellitus (T2DM)[1]. Increasing CAG repeat number within exon 1 of the androgen receptor gene associates with increased androgen receptor resistance/insulin resistance [2]. We here investigated the link between CAG repeat number and metabolic/cardiovascular outcomes in T2DM men.

Methods: We determined in a 14-year follow-up cohort of 274 T2DM Caucasian men in Salford UK, the association between baseline androgen status/CAG repeat number (determined by PCR followed by Sequenom sequencing) and metabolic trajectory plus mortality.

Results: Lower baseline 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) and higher HbA1c 2016. Higher baseline CAG repeat number associated with higher follow-up BMI in 2016 - each unit increase in CAG repeat associated with 0.43 increment in BMI 2016. At an average 14 year follow-up 55.8% of hypogonadal men had died vs 36.1% of eugonadal men (p = 0.001). 72% of deaths were from cardiovascular causes. 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 (Figure 1). This was independent of baseline testosterone.

Conclusion: A higher number of CAG repeats at the testosterone receptor gene associates with higher future BMI/increased HbA1c. There was a ‘u’ shaped relation between CAG repeat number and mortality rate. CAG repeat number may become part of cardiovascular risk assessment in T2DM men.

CAG_cat	Mortality	Proportional mortality rate	Lower bound	Upper bound
≤20	40	43	32	53
21	12	24	13	39
22–23	28	50	36	64
>23	34	45	34	57

Copyright

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

References

[1]V Muraleedharan, H Marsh, D Kapoor, KS Channer, and TH Jones, Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes, Eur J Endocrinol, Vol. 169, 2013, pp. 725-33.

[2]RD Stanworth, D Kapoor, KS Channer, and TH Jones, Androgen receptor CAG repeat polymorphism is associated with serum testosterone levels, obesity and serum leptin in men with type 2 diabetes, Eur J Endocrinol, Vol. 159, 2008, pp. 739-46.

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Journal: Artery Research
Volume-Issue: 25 - Supplement 1
Pages: S178 - S179
Publication Date: 2020/02/17
ISSN (Online): 1876-4401
ISSN (Print): 1872-9312
DOI: 10.2991/artres.k.191224.163 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

Cite this article

ris enw bib

TY  - JOUR
AU  - Adrian Heald
AU  - Ghasem Yadegarfar
AU  - Mark Livingston
AU  - Helene Fachim
AU  - Ram Prakash Narayanan
AU  - Mark Lunt
AU  - Kirk Siddals
AU  - Gabriela Cortes
AU  - Martin Gibson
AU  - Rachelle Donn
AU  - Simon Anderson
AU  - Geoff Hackett
AU  - Hugh Jones
PY  - 2020
DA  - 2020/02/17
TI  - P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study
JO  - Artery Research
SP  - S178
EP  - S179
VL  - 25
IS  - Supplement 1
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.191224.163
DO  - 10.2991/artres.k.191224.163
ID  - Heald2020
ER  -

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