Vitamin D deficiency is a common finding in individuals with cystic fibrosis (CF), despite routine supplementation. Hypovitaminosis D is often the result of fat malabsorption, but other contributors include increased latitude, poor nutritional intake, decreased sun exposure, impaired hydroxylation of vitamin D, and nonadherence to the prescribed vitamin D regimen. Vitamin D is critical for calcium homeostasis and optimal skeletal health, and vitamin D deficiency in CF can lead to skeletal complications of osteopenia and osteoporosis. Over time, our understanding of treatment regimens for vitamin D deficiency in CF has evolved, leading to recommendations for higher doses of vitamin D to achieve target levels of circulating 25-hydroxyvitamin D. There is also some evidence that vitamin D deficiency may have non-skeletal consequences such as an increase in pulmonary exacerbations. The exact mechanisms involved in the non-skeletal complications of vitamin D deficiency are not clearly understood, but may involve the innate immune system. Future clinical studies are needed to help address whether vitamin D has a role in CF beyond skeletal health.

Women with cystic fibrosis (CF) are living longer and healthier lives, and opportunities for childbearing are increasingly promising. However, this population can also face sexual and reproductive health concerns, including menstrual irregularities, unplanned pregnancies, infertility and pregnancy complications. Additionally, more women are entering menopause and are at risk for the consequences of estrogen deficiency. The exact mechanisms involved in female reproductive health conditions in CF are not clearly understood, but are thought to include cystic fibrosis transmembrane regulator (CFTR)-mediated abnormalities, changes in female sex hormones, and other CF health-related factors. In the era of CFTR modulator therapy, new data are necessary to understand the impact of CFTR modulation on contraceptive effectiveness, fertility, and pregnancy outcomes to help guide future clinical care. This article reviews the current scientific knowledge of major reproductive health issues for women with CF.

Background Risk of type 2 diabetes mellitus (T2DM) in transgender and gender diverse (TGD) persons, especially those receiving gender-affirming hormone therapy (GAHT) is an area of clinical and research importance. Methods We used data from an electronic health record-based cohort study of persons 18 years and older enrolled in 3 integrated health care systems. The cohort included 2869 transfeminine members matched to 28 300 cisgender women and 28 258 cisgender men on age, race/ethnicity, calendar year, and site, and 2133 transmasculine members similarly matched to 20 997 cisgender women and 20 964 cisgender men. Cohort ascertainment spanned 9 years from 2006 through 2014 and follow-up extended through 2016. Data on T2DM incidence and prevalence were analyzed using Cox proportional hazards and logistic regression models, respectively. All analyses controlled for body mass index. Results Both prevalent and incident T2DM was more common in the transfeminine cohort relative to cisgender female referents with odds ratio and hazard ratio (95% CI) estimates of 1.3 (1.1-1.5) and 1.4 (1.1-1.8), respectively. No significant differences in prevalence or incidence of T2DM were observed across the remaining comparison groups, both overall and in TGD persons with evidence of GAHT receipt. Conclusion Although transfeminine people may be at higher risk for T2DM compared with cisgender females, the corresponding difference relative to cisgender males is not discernable. Moreover, there is little evidence that T2DM occurrence in either transfeminine or transmasculine persons is attributable to GAHT use.

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Cystic fibrosis (CF) is a recessive disorder arising from mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is expressed in numerous tissues, with high expression in the airways, small and large intestine, pancreatic and hepatobiliary ducts, and male reproductive tract. CFTR loss in these tissues disrupts regulation of salt, bicarbonate, and water balance across their epithelia, resulting in a systemic disorder with progressive organ dysfunction and damage. Pancreatic exocrine damage ultimately manifests as pancreatic exocrine insufficiency that begins as early as infancy. Pancreatic remodeling accompanies this early damage, during which abnormal glucose tolerance can be observed in toddlers. With increasing age, however, insulin secretion defects progress such that CF-related diabetes (CFRD) occurs in 20% of teens and up to half of adults with CF. The relevance of CFRD is highlighted by its association with increased morbidity, mortality, and patient burden. While clinical research on CFRD has greatly assisted in the care of individuals with CFRD, key knowledge gaps on CFRD pathogenesis remain. Furthermore, the wide use of CFTR modulators to restore CFTR activity is changing the CFRD clinical landscape and the field’s understanding of CFRD pathogenesis. For these reasons, the National Institute of Diabetes and Digestive and Kidney Diseases and the Cystic Fibrosis Foundation sponsored a CFRD Scientific Workshop, 23–25 June 2021, to define knowledge gaps and needed research areas. This article describes the findings from this workshop and plots a path for CFRD research that is needed over the next decade.