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The Effect of Exenatide on Cardiovascular Risk Markers in Women With Polycystic Ovary Syndrome.

Abstract

Background:

Polycystic ovary syndrome (PCOS) is associated with an adverse cardiovascular risk profile including a prothrombotic state. Exenatide has been shown to be effective at improving insulin sensitivity and weight loss in PCOS; therefore this study was undertaken to assess its effects on weight, endothelial function, inflammatory markers, and fibrin structure/function in overweight/obese women with PCOS.

Methods:

Thirty overweight/obese anovulatory women with all 3 Rotterdam criteria received exenatide 5 mcg bd for 4 weeks then 10 mcg bd for 12 weeks. The primary outcome was change in weight; secondary outcomes were changes in endothelial function [Reactive Hyperemia-Peripheral Arterial Tonometry (RH-PAT)], serum endothelial markers (ICAM-1, VCAM-1, E-selectin, and P-selectin), change in inflammation (hsCRP), and alteration in clot structure and function [maximum absorbance (MA), and time from full clot formation to 50% lysis (LT)].

Results:

Twenty patients completed the study. Exenatide reduced weight 111.8 ± 4.8 to 108.6 ± 4.6 kg p = 0.003. Serum endothelial markers changed with a reduction in ICAM-1 (247.2 ± 12.9 to 231.3 ± 11.5 ng/ml p = 0.02), p-selectin (101.1 ± 8.2 to 87.4 ± 6.6 ng/ml p = 0.01), and e-selectin (38.5 ± 3.3 to 33.6 ± 2.6 ng/ml p = 0.03), without an overt change in endothelial function. Inflammation improved (CRP; 8.5 ± 1.4 to 5.6 ± 0.8 mmol/L p = 0.001), there was a reduction in clot function (LT; 2,987 ± 494 to 1,926 ± 321 s p = 0.02) but not clot structure.

Conclusion:

Exenatide caused a 3% reduction in weight, improved serum markers of endothelial function, inflammation, and clot function reflecting an improvement in cardiovascular risk indices in these women with PCOS. This suggests exenatide could be an effective treatment for obese women with PCOS. Clinical Trial Registration: ISRCTN81902209.

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  • Authors+Show Affiliations

    ,

    Department of Diabetes and Endocrinology, University of Hull, Hull, United Kingdom.

    ,

    Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Heslington, United Kingdom.

    ,

    Department of Sports Science, University of Hull, Hull, United Kingdom.

    ,

    Department of Ultrasound, Hull and East Yorkshire Women's and Children's Hospital, Hull, United Kingdom.

    ,

    Division of Cardiovascular and Diabetes Research, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom.

    ,

    Sidra Medical Research Centre, Doha, Qatar.

    Weill Cornell Medicine Qatar, Education City, Doha, Qatar. Royal College of Surgeons in Ireland (Bahrain), Al Muharraq, Bahrain.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31001199

    Citation

    Dawson, Alison J., et al. "The Effect of Exenatide On Cardiovascular Risk Markers in Women With Polycystic Ovary Syndrome." Frontiers in Endocrinology, vol. 10, 2019, p. 189.
    Dawson AJ, Sathyapalan T, Vince R, et al. The Effect of Exenatide on Cardiovascular Risk Markers in Women With Polycystic Ovary Syndrome. Front Endocrinol (Lausanne). 2019;10:189.
    Dawson, A. J., Sathyapalan, T., Vince, R., Coady, A. M., Ajjan, R. A., Kilpatrick, E. S., & Atkin, S. L. (2019). The Effect of Exenatide on Cardiovascular Risk Markers in Women With Polycystic Ovary Syndrome. Frontiers in Endocrinology, 10, p. 189. doi:10.3389/fendo.2019.00189.
    Dawson AJ, et al. The Effect of Exenatide On Cardiovascular Risk Markers in Women With Polycystic Ovary Syndrome. Front Endocrinol (Lausanne). 2019;10:189. PubMed PMID: 31001199.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The Effect of Exenatide on Cardiovascular Risk Markers in Women With Polycystic Ovary Syndrome. AU - Dawson,Alison J, AU - Sathyapalan,Thozhukat, AU - Vince,Rebecca, AU - Coady,Anne-Marie, AU - Ajjan,Ramzi A, AU - Kilpatrick,Eric S, AU - Atkin,Stephen L, Y1 - 2019/04/02/ PY - 2018/11/04/received PY - 2019/03/06/accepted PY - 2019/4/20/entrez PY - 2019/4/20/pubmed PY - 2019/4/20/medline KW - GLP-1 receptor agonists KW - blood clot function KW - cardiovascular risk KW - endothelial function KW - exenatide KW - inflammation KW - polycystic ovary syndrome SP - 189 EP - 189 JF - Frontiers in endocrinology JO - Front Endocrinol (Lausanne) VL - 10 N2 - Background: Polycystic ovary syndrome (PCOS) is associated with an adverse cardiovascular risk profile including a prothrombotic state. Exenatide has been shown to be effective at improving insulin sensitivity and weight loss in PCOS; therefore this study was undertaken to assess its effects on weight, endothelial function, inflammatory markers, and fibrin structure/function in overweight/obese women with PCOS. Methods: Thirty overweight/obese anovulatory women with all 3 Rotterdam criteria received exenatide 5 mcg bd for 4 weeks then 10 mcg bd for 12 weeks. The primary outcome was change in weight; secondary outcomes were changes in endothelial function [Reactive Hyperemia-Peripheral Arterial Tonometry (RH-PAT)], serum endothelial markers (ICAM-1, VCAM-1, E-selectin, and P-selectin), change in inflammation (hsCRP), and alteration in clot structure and function [maximum absorbance (MA), and time from full clot formation to 50% lysis (LT)]. Results: Twenty patients completed the study. Exenatide reduced weight 111.8 ± 4.8 to 108.6 ± 4.6 kg p = 0.003. Serum endothelial markers changed with a reduction in ICAM-1 (247.2 ± 12.9 to 231.3 ± 11.5 ng/ml p = 0.02), p-selectin (101.1 ± 8.2 to 87.4 ± 6.6 ng/ml p = 0.01), and e-selectin (38.5 ± 3.3 to 33.6 ± 2.6 ng/ml p = 0.03), without an overt change in endothelial function. Inflammation improved (CRP; 8.5 ± 1.4 to 5.6 ± 0.8 mmol/L p = 0.001), there was a reduction in clot function (LT; 2,987 ± 494 to 1,926 ± 321 s p = 0.02) but not clot structure. Conclusion: Exenatide caused a 3% reduction in weight, improved serum markers of endothelial function, inflammation, and clot function reflecting an improvement in cardiovascular risk indices in these women with PCOS. This suggests exenatide could be an effective treatment for obese women with PCOS. Clinical Trial Registration: ISRCTN81902209. SN - 1664-2392 UR - https://www.unboundmedicine.com/medline/citation/31001199/The_Effect_of_Exenatide_on_Cardiovascular_Risk_Markers_in_Women_With_Polycystic_Ovary_Syndrome_ L2 - https://dx.doi.org/10.3389/fendo.2019.00189 DB - PRIME DP - Unbound Medicine ER -