MON-575 Association of CFRD Development Among Females with CF Who Use Hormonal Contraception

Abstract Disclosure: F.N. Khan: None. A. Magaret: None. C. Hsu: None. R. Jain: None. T. Kazmerski: None. J. Taylor-Cousar: None. E. Godfrey: None. Background: Cystic fibrosis (CF)-related diabetes (CFRD) is the most common co-morbidity among people with CF. Multiple risk factors, including metabolic risk factors, insulin sensitivity, and glycemic control have been implicated in the development of CFRD. Research suggests the effects of combined (containing both estrogen and progestin) hormonal contraception (CHC) can negatively affect insulin sensitivity. This study aims to better understand the association between HC use and developing CFRD in females with CF. Methods: Between January 2021 to April 2022 we recruited females ages 18-45 years with CF from 10 CF centers to complete a self-administered retrospective online questionnaire regarding contraceptive use from 2008 to survey completion year. We linked survey responses to the CF Foundation’s Patient Registry covering the same years as the survey. We examined potential associations with CFRD, incidence of new CFRD diagnosis, and CFRD’s association with HC using Cox regression adjusted for age, body mass index, CF modulator use, and socioeconomic status (as college degree). Results: In our observational cohort of 561 persons completing the survey, the incidence of CFRD was low at 145 cases per 3674 person-years (p-y), or 3.9 cases per 100 p-y. In sensitivity analysis, using either clinical or laboratory definitions of CFRD (fasting blood glucose ≥126, or two-hour oral glucose tolerance test ≥200, or HbA1c ≥6.5%), we noted 178 cases in 3413 p-y, for an incidence of 5.2 cases per 100 p-y. Neither weight nor age were found to be associated with CFRD incidence, though a marginal trend was observed for obesity to be protective. While glucose measurement was infrequently performed, elevated plasma glucose, 2-hour oral glucose tolerance test, and HbA1c were all significantly associated with CFRD diagnosis. CFTR genotype, a known risk factor for the development of CFRD, was dissimilar in modulator versus non-modulator users. Compared to non-modulator users, CF modulator use was not associated with increased CFRD (HR 0.72, 95% CI .39-1.33). Among non-modulator users, CFRD incidence was significantly associated with CHC use (HR = 1.53, 95% CI 1.03-2.27). CFRD incidence was not significantly associated with using progestin-only HC among non-modulator users or among modulator users using either CHC or progestin-only HC. Conclusion: Combined HC was associated with a higher incidence of CFRD among non-modulator users. However, given the observational nature of this study and other recall limitations, it may not be the contraceptives themselves behind this increased risk, but other associated factors. More research is needed to better understand the relationship between CHC and CFRD. Presentation: Monday, July 14, 2025