P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study
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 invest...
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Artery Research |
| Online Access: | https://doi.org/10.2991/artres.k-191224.163 |
| _version_ | 1797275312015278080 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Adrian Heald |
| collection | DOAJ |
| description | 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. Figure 1 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 |
| first_indexed | 2024-03-07T15:12:27Z |
| format | Article |
| id | doaj.art-d6140b3741864920bbf1eced1d345355 |
| institution | Directory Open Access Journal |
| issn | 1872-9312 1876-4401 |
| language | English |
| last_indexed | 2024-03-07T15:12:27Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Artery Research |
| spelling | doaj.art-d6140b3741864920bbf1eced1d3453552024-03-05T18:15:54ZengBMCArtery Research1872-93121876-44012020-02-0125S1S178S17910.2991/artres.k-191224.163P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up StudyAdrian Heald0Ghasem Yadegarfar1Mark Livingston2Helene Fachim3Ram Prakash Narayanan4Mark Lunt5Kirk Siddals6Gabriela Cortes7Martin Gibson8Rachelle Donn9Simon Anderson10Geoff Hackett11Hugh Jones12Salford Royal HospitalUniversity of ManchesterWalsall Manor HospitalSalford Royal HospitalUniversity of ManchesterUniversity of ManchesterUniversity of ManchesterHigh Speciality Regional Hospital of IxtapalucaSalford Royal HospitalUniversity of ManchesterUniversity of the West IndiesHeartlands HospitalUniversity of SheffieldAbstract 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. Figure 1 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 57https://doi.org/10.2991/artres.k-191224.163 |
| spellingShingle | 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 P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study Artery Research |
| title | P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study |
| title_full | P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study |
| title_fullStr | P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study |
| title_full_unstemmed | P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study |
| title_short | P142 Androgen Receptor Reduced Sensitivity is Associated with Cardiovascular Mortality in Men with Type 2 Diabetes - A 14-year Follow up Study |
| title_sort | p142 androgen receptor reduced sensitivity is associated with cardiovascular mortality in men with type 2 diabetes a 14 year follow up study |
| url | https://doi.org/10.2991/artres.k-191224.163 |
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