Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes
Abstract Background Endogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenou...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-01966-6 |
| _version_ | 1797578305916895232 |
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| author | Abigayle B. Simon Cassandra C. Derella Marsha Blackburn Jeffrey Thomas Lawrence C. Layman Matthew S. Nicholson Jennifer Waller Ahmed Elmarakby Karim M. Saad Ryan A. Harris |
| author_facet | Abigayle B. Simon Cassandra C. Derella Marsha Blackburn Jeffrey Thomas Lawrence C. Layman Matthew S. Nicholson Jennifer Waller Ahmed Elmarakby Karim M. Saad Ryan A. Harris |
| author_sort | Abigayle B. Simon |
| collection | DOAJ |
| description | Abstract Background Endogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenous estradiol on endothelial function in women with type 1 diabetes. Method 32 women with type 1 diabetes (HbA1c = 8.6 ± 1.7%) and 25 apparently healthy women (HbA1c = 5.2 ± 0.3%) participated. Flow-mediated dilation (FMD), a bioassay of nitric-oxide bioavailability and endothelial function was performed during menses (M) and the late follicular (LF) phase of the menstrual cycle to represent low and high concentrations of estrogen, respectively. In addition, a venous blood sample was collected at each visit to determine circulating concentrations of estradiol, thiobarbituric acid reactive substances (TBARS), and nitrate/nitrite (NOx), biomarkers of oxidative stress and nitric oxide, respectively. Data were collected in (1) 9 additional women with type 1 diabetes using oral hormonal birth control (HBC) (HbA1c = 8.3 ± 2.1%) during the placebo pill week and second active pill week, and (2) a subgroup of 9 demographically matched women with type 1 diabetes not using HBC (HbA1c = 8.9 ± 2.1%). Results Overall, estradiol was significantly increased during the LF phase compared to M in both type 1 diabetes (Δestradiol = 75 ± 86 pg/mL) and controls (Δestradiol = 71 ± 76 pg/mL); however, an increase in TBARS was only observed in patients with type 1 diabetes (ΔTBARS = 3 ± 13 µM) compared to controls (ΔTBARS = 0 ± 4 µM). FMD was similar (p = 0.406) between groups at M. In addition, FMD increased significantly from M to the LF phase in controls (p = 0.024), whereas a decrease was observed in type 1 diabetes. FMD was greater (p = 0.015) in patients using HBC compared to those not on HBC, independent of menstrual cycle phase. Conclusion Endogenous estradiol increases oxidative stress and contributes to endothelial dysfunction in women with diabetes. Additionally, HBC use appears to be beneficial to endothelial function in type 1 diabetes. |
| first_indexed | 2024-03-10T22:20:03Z |
| format | Article |
| id | doaj.art-210b6d7177b144c1bc5fd9f22fd4ad8d |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-10T22:20:03Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-210b6d7177b144c1bc5fd9f22fd4ad8d2023-11-19T12:17:33ZengBMCCardiovascular Diabetology1475-28402023-09-0122111210.1186/s12933-023-01966-6Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetesAbigayle B. Simon0Cassandra C. Derella1Marsha Blackburn2Jeffrey Thomas3Lawrence C. Layman4Matthew S. Nicholson5Jennifer Waller6Ahmed Elmarakby7Karim M. Saad8Ryan A. Harris9Georgia Prevention Institute, Medical College of Georgia, Augusta UniversityGeorgia Prevention Institute, Medical College of Georgia, Augusta UniversityGeorgia Prevention Institute, Medical College of Georgia, Augusta UniversityGeorgia Prevention Institute, Medical College of Georgia, Augusta UniversitySection of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia, Augusta UniversityDepartment of Endocrinology, Medical College of Georgia, Augusta UniversityDepartment of Biostatistics and Data Science, Medical College of Georgia, Augusta UniversityDepartment of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta UniversityDepartment of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta UniversityGeorgia Prevention Institute, Medical College of Georgia, Augusta UniversityAbstract Background Endogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenous estradiol on endothelial function in women with type 1 diabetes. Method 32 women with type 1 diabetes (HbA1c = 8.6 ± 1.7%) and 25 apparently healthy women (HbA1c = 5.2 ± 0.3%) participated. Flow-mediated dilation (FMD), a bioassay of nitric-oxide bioavailability and endothelial function was performed during menses (M) and the late follicular (LF) phase of the menstrual cycle to represent low and high concentrations of estrogen, respectively. In addition, a venous blood sample was collected at each visit to determine circulating concentrations of estradiol, thiobarbituric acid reactive substances (TBARS), and nitrate/nitrite (NOx), biomarkers of oxidative stress and nitric oxide, respectively. Data were collected in (1) 9 additional women with type 1 diabetes using oral hormonal birth control (HBC) (HbA1c = 8.3 ± 2.1%) during the placebo pill week and second active pill week, and (2) a subgroup of 9 demographically matched women with type 1 diabetes not using HBC (HbA1c = 8.9 ± 2.1%). Results Overall, estradiol was significantly increased during the LF phase compared to M in both type 1 diabetes (Δestradiol = 75 ± 86 pg/mL) and controls (Δestradiol = 71 ± 76 pg/mL); however, an increase in TBARS was only observed in patients with type 1 diabetes (ΔTBARS = 3 ± 13 µM) compared to controls (ΔTBARS = 0 ± 4 µM). FMD was similar (p = 0.406) between groups at M. In addition, FMD increased significantly from M to the LF phase in controls (p = 0.024), whereas a decrease was observed in type 1 diabetes. FMD was greater (p = 0.015) in patients using HBC compared to those not on HBC, independent of menstrual cycle phase. Conclusion Endogenous estradiol increases oxidative stress and contributes to endothelial dysfunction in women with diabetes. Additionally, HBC use appears to be beneficial to endothelial function in type 1 diabetes.https://doi.org/10.1186/s12933-023-01966-6DiabetesEndothelial functionEstrogenOral contraceptives |
| spellingShingle | Abigayle B. Simon Cassandra C. Derella Marsha Blackburn Jeffrey Thomas Lawrence C. Layman Matthew S. Nicholson Jennifer Waller Ahmed Elmarakby Karim M. Saad Ryan A. Harris Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes Cardiovascular Diabetology Diabetes Endothelial function Estrogen Oral contraceptives |
| title | Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes |
| title_full | Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes |
| title_fullStr | Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes |
| title_full_unstemmed | Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes |
| title_short | Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes |
| title_sort | endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes |
| topic | Diabetes Endothelial function Estrogen Oral contraceptives |
| url | https://doi.org/10.1186/s12933-023-01966-6 |
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