DiaComp Funded Abstracts
Program Application Abstract
The Timing of the Onset of Hormone Replacement Therapy and Its Effect on Cardiovascular Risk in Women With Type 1 Diabetes
(University of Colorado at Denver and Health Sciences Center)
Summer Student Program
Women with diabetes have a greater chance of developing cardiovascular disease (CVD) than their nondiabetic counterparts. CVD risk in women increases at the time of menopause. Hormone replacement therapy (HRT) has been demonstrated to favorably influence several risk factors in post-menopausal diabetic patients including dyslipidemia, hypertension, and endothelial dysfunction. However, while estrogen may delay the earlier stages of atherosclerosis through promising effects on endothelial function and blood lipids, it may provoke acute events in already atherosclerotic arteries through procoagulant and inflammatory mechanisms. The purpose of this study was to determine whether the timing of the onset of HRT therapy is associated with coronary artery calcification (CAC) progression in T1D postmenopausal women. Patients included 516 women (254 T1D, 262 Non-DM) between the ages of 19 and 55 yr. who had CAC measured twice by electron beam tomography. This was a prospective study, and data were collected between January 2014 and June 2016. We used a mixed model to examine the effect of HRT use and timing on square root-transformed CAC volume. We adjusted for diabetes, HRT status (never, pre-menopause or post-menopause), birth control years of use (never, 1-5 years, 6-10 years, or 10+ years), years post-menopause at the time of the visit, age, blood pressure, cholesterol, BMI, diabetes*HRT status interaction, and diabetes*BCP status interaction. We excluded women who were premenopausal at both time points from the analysis. Among all women, diabetes was significantly associated with a 6.89- point increase in the progression of CAC square root volume (p<0.0001). Non-DM women who used HRT pre-menopause had the lowest CVD risk out of all of the women. Non-DM women who initiated HRT pre-menopause tended to have a progression of coronary artery calcium square root volume that was 3.07 points lower compared to non-DM women who initiated HRT post-menopause (p=0.0395) and 2.36 points lower compared to non-DM women who never used HRT (p=0.0086). T1D women who never initiated HRT tended to have a progression of coronary artery calcium square root volume that was 6.43 points lower compared to T1D women who initiated HRT post-menopause (p<0.001). T1D women who used HRT post- menopause had the highest estimated CAC square root volume progression (13.41, p<0.0001), followed by T1D women who used HRT pre-menopause (6.92, p<0.0001). Women with T1D experienced greater CAC square root volume progression during the study than non-DM women, and while HRT taken prior to menopause was protective in Non-DM women, any HRT use and particularly post-menopausal use increased the progression of CAC. It’s probable that by the time that the T1D women in the study initiated HRT, they were already experiencing more advanced stages of atherosclerosis seen at earlier ages in T1D and as indicated by the higher CAC square root volume seen at visit 3 in the T1D women. Hence, according to the Timing Hypothesis, the HRT could have accelerated their atherosclerosis. Further studies should focus on studying the effects of the onset of HRT in T1D women without and without extensive atherosclerosis to determine if HRT increases CVD risk among T1D who already have disease.
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