Social determinants of health, cystic fibrosis-related diabetes, and mental health in adult patients with cystic fibrosis: a critical synthesis of narrative review

Abstract

The population of adults with cystic fibrosis (CF) exceeds that of the pediatric CF population, and life expectancy for people with CF (PwCF) continues to improve, resulting in an adult CF population with chronic extrapulmonary comorbid conditions, including CF-related diabetes (CFRD), a common complication affecting roughly 50% of PwCF, as well as mental health disorders, including depression and generalized anxiety. These comorbidities have been strongly associated with increased risk of progressive lung disease, impaired quality of life, and increased risk of acute exacerbations requiring healthcare utilization. These risks disproportionately affect PwCF who are from ethnic minorities and are often genetically ineligible for novel treatments. Social determinants of health (SDOH) are related to and contribute to health disparities in PwCF. To reduce the impact of SDOH on health-related disparities in this population, PwCF needs greater awareness of associated factors to develop interventions that can improve care. This narrative review critically synthesizes the available literature on the complex intersections of social determinants of health, mental health, and concomitant CFRD that affect health outcomes for PwCF.

Plain language summary

Social determinants of health, cystic fibrosis-related diabetes, and mental health in adult patients with cystic fibrosis: A critical synthesis of narrative review

Cystic fibrosis (CF) is a chronic respiratory condition that makes breathing difficult. People with CF, about half of them suffer from diabetic related conditions which worsens their respiratory symptoms, impairing quality of life and increasing disability and healthcare utilization. Social determinants of health are associated with health disparities in patients with cystic fibrosis and disproportionately affect those from ethnic minorities and those from low socioeconomic status background. In addition, cystic fibrosis related to diabetes requires extra help to manage and alleviate their burden. This narrative review highlights the gap in the service of managing cystic fibrosis related to diabetes and heavily affects those from ethnic minorities. Further research is needed to develop better innovative interventions to improve care for this vulnerable patient group.

Introduction

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in limited production and dysfunction of the CFTR protein. CF disease commonly results in clinically significant symptomatology across multiple organ systems, typically dominated by digestive and sinopulmonary pathology.^1,2 Fortunately, life expectancy for people with cystic fibrosis (PwCF) has significantly improved and now exceeds 60 years in high income developed countries, primarily as a result of therapeutic advancements including the development of CFTR modulator therapies including Elexacaftor-Tezacaftor-Ivacaftor (ETI)^2–4 In addition to CFTR modulators, pancreatic enzyme replacement therapy, airway clearance, and antibiotics have significantly improved lung function and quality of life (QoL).^1,5–9 Despite these improvements in QoL and longevity, which have primarily focused on preventing loss of lung function, a significant portion of adult PwCF suffer from extrapulmonary comorbidities, including CF-related diabetes (CFRD) and mental health disorders.^10,11

CFRD is a common extrapulmonary manifestation of CF affecting 27%–50% of adult PwCF and negatively affects long-term prognosis and QoL. ¹² A previous retrospective, cross-sectional study in adult PwCF examined the influence of diabetes on mental health and identified that almost half (48%) of patients with CFRD had comorbid depressive symptoms compared to 28% of patients without CFRD. ¹³ Untreated depression in PwCF (with or without CFRD) was associated with poor compliance with medical treatment, early dropout from pulmonary rehabilitation, impaired QoL, increased risk of pulmonary exacerbations, elevated proinflammatory biomarkers, and hospital readmissions.^14–16

Social determinants of health (SDOH) are nonmedical factors that influence health outcomes. SDOH are defined by the environment where individuals are born, live, worship, and age. SDOH are commonly categorized into five domains: economic stability, education access, healthcare access, neighborhood and built environment (e.g., structurally designed homes to have access to parks or green space), and social and community context.^17,18 Unmet SDOH contributes to increased healthcare disparities in patients with severe chronic respiratory diseases, including CF ¹⁹ and PwCF from socioeconomically disadvantaged backgrounds, who have worse health outcomes and an increased risk of dying younger than those in more advantaged positions. ¹⁹

Growing evidence shows that lower socioeconomic status (SES) has a deleterious effect on individuals’ nutritional status and correlates with lung function impairment, and increased risk of exacerbations, hospitalizations, and comorbidities in PwCF^20,21 and chronic obstructive pulmonary disease. ²² To date, little evidence evaluates the impact of SDOH on the management of depressive and anxiety symptoms among adult PwCF with concomitant CFRD. Thus, addressing the health disparities is paramount as they are closely related to SDOH. Hence, creating awareness, a better understanding of factors that are related to disparities, and identifying the most vulnerable groups within PwCF will be a first step to develop effective interventions. This narrative review critically synthesizes the available literature and provides an overview of disparities focusing on the interplay of SDOH in PwCF and concomitant CFRD and the impact on mental health.

Methods

This is a critical synthesis of a narrative review. The keywords used were “social determinants of health” and “cystic fibrosis related to diabetes,” “depression,” and “anxiety,” and “mental health” were searched in PubMed and searched from inception to November 13, 2025. This achieved no results. We also searched for the Cochrane Library, again from inception to 13th November. This achieved no results. We searched in the Google Scholar engine and achieved four relevant articles. We have checked the references of the published literature and extracted a number of relevant articles for our critical synthesis. This review is based on previously conducted studies with human participants only. We also checked published reviews and consensus statements to complement our synthesis.

SDOH and CF

Ethnicity and SES

SES incorporates an individual’s social or economic standing and represents a composite measure of income, education, and occupation. Therefore, low SES is associated with decreased academic attainment and lower household income. For PwCF, lower SES has been associated with increased disease severity, greater healthcare utilization, impaired QoL, and reduced survival.^21,23 To date, there are over 2000 identified disease-causing mutations in the CFTR gene, and PwCF who are ethnic minorities are more likely than their Caucasian counterparts to harbor genetic variances in the CFTR gene that are not identified using standard newborn screening panels, leading to disparities in care, including delayed diagnosis and treatment. ²⁴ In addition, PwCF who are ethnic minorities are more likely to have CFTR mutations that are not responsive to modern CFTR modulator therapies. Thus, despite therapeutic advances, PwCF who are racial and ethnic minorities, from low socioeconomic status, and/or female sex continue to experience worse clinical outcomes. ²⁵ Furthermore, controlling for SES and disease severity, African American and Hispanic PwCF reported worse emotional and social functioning compared to Caucasian PwCF. ²⁵ Also, using the CF Foundation Patient Registry, Hergenroeder and co-workers assessed PwCF aged 12 years and older (n = 17, 183) and sought to identify factors that are associated with the delay in initiation of ETI. Their findings indicate that having public health insurance and black and Hispanic ethnicity were associated with a longer wait time to first ETI prescription compared to Caucasians. ²⁶ A separate retrospective study in the US ²⁷ using data from the Cystic Fibrosis Patient Registry from 2010 to 2014 demonstrated 27% higher death rates for Hispanic PwCF compared with non-Hispanics after controlling for SES.

In the US, CF care centers are required to have a social worker as a member of their care team for accreditation and standards; however, formalized screening for social needs is not yet a formalized component of the CF care model. Jennings and co-authors ²⁸ screened adult PwCF for the prevalence of unmet health-related social needs using a survey that assessed social risk factors across eight domains (housing, food, transportation, utilities, healthcare access, medication access, income/employment, and education). One hundred thirty-two PwCF were recruited from outpatient clinics at a large academic center in the US, and 42% of individuals screened positive for unmet needs in one or more SDOH domains. Those who screened positive for SDOH and requested assistance were referred to external agencies (e.g., housing reported needs, food insecurity, transportation problems, income, and employment access) and received appropriate support. This quality improvement project showed that screening for SDOH and providing appropriate interventions to mitigate social difficulties in adult PwCF is a feasible component of the CF care model.

An observational study that examined the impact of SES on adherence to airway clearance therapy (using the high-frequency chest wall oscillation therapy for 4–6 weeks) in pediatric CF children was carried out with 12-months follow-up. Better adherence to airway clearance therapy was associated with higher household income (> $50,000) compared to lower income. ²⁹ In addition, households with a paternal college education, higher income (> $100,000), and unexposed to tobacco smoke were independently associated with higher lung function in children with cystic fibrosis. In contrast, CF children exposed to environmental tobacco smoke and household income < $40.000 had lower lung function, elevated respiratory symptoms or wheezes, and poorer nutritional status compared to children with higher income households. ³⁰ This underlies the importance of educating parents and children about smoking-free environment and encouraging parents to stop smoking at home.

Smoking exposure during Elexacaftor/Tezacaftor/Ivacaftor (ETI) treatment: ETI improves lung function and reduces acute exacerbation in PwCF. A retrospective ³¹ longitudinal analysis of data from the Cystic Fibrosis Foundation Patient Registry (2019–2021) on PwCF aged ⩾ 12 years (n = 15,000) examined the efficacy of ETI on clinically relevant outcomes over a 12-month follow-up. The findings indicate the benefit of ETI was not sustained beyond 6 months among those PwCF with tobacco smoking exposure (TSE). The TSE group did not gain as many significant benefits as the non-TSE group from ETI. This is due to the deleterious impact of cigarette smoking on CFTR function. ³² PwCF exposed to TSE had twice the odds of exhibiting pulmonary exacerbations compared to unexposed counterparts. Black PwCF were 53% percent increased risk for pulmonary exacerbations compared to White in the preceding 12-months. In addition, children with PwCF exposed to TSE and from low SES households are independently associated with progressive lung function decline. ³³ Therefore, smoking cessation and strategies to reduce passive smoking exposure should be highlighted and treated in routine pediatric and adult CF care, which may help to reduce pulmonary-related exacerbations and respiratory symptoms. ³⁴

Neighborhood and physical environment: Environmental factors such as traffic related air pollution exposure to elemental carbon attributable to traffic sources coupled with community level-material deprivation (poverty, education, housing, and healthcare access), were associated with a rapid decline in lung function in PwCF.^35,36 Similarly, higher environmental adversity (a composite score for geo-markers by ZIP code measuring air pollution and respiratory hazards, greenspace, crime, and socioeconomic deprivation) has been associated with increased risk of rapid decline in lung function and mortality.^34,35 Oates and colleagues ³⁷ observed that in pediatric patients with CF (n = 231) living in households of higher area-level deprivation (measured by area deprivation index, 1–100, a higher score implies greater deprivation), was associated with rural residence, lack of parental college education, and lower household income. Furthermore, the study underscored that high neighborhood deprivation was associated with a twofold increase in the odds of CF children having methicillin-resistant Staphylococcus aureus infection (MRSA). This highlights the importance of preventative strategies (e.g., education and hygiene) and treatment plans by healthcare providers to reduce the occurrence of MRSA infection, which is a worthy endeavor.

Geographical location: There is some evidence to suggest that healthcare disparities exist between rural and urban CF populations, and rural CF patients tend to have poorer outcomes (e.g., elevated risk of mortality). ³⁸ The exact causes are unclear. Living in rural areas might be a challenge for PwCF, and distance might play a role by limiting individuals to have access to specialized CF care centers. ³⁸ In a separate study, in Canada, British Columbia, adult CF patients who lived more than 2.5 h from a CF center were less likely to attend quarterly clinic visits, and at heightened risk of lung function decline compared to those within 45-minutes travel distance. ³⁹ In the US, transferring from CF pediatric care to adults’ CF care happens between the ages of 18 and 21 years old. However, care transition is not always smooth for PwCF. The risk factors that are associated with prolonged gaps in care were younger age at transfer, lack of health insurance, and relocation far away from the specialized CF center(s). ⁴⁰ Hence, care coordination is vital between individuals and healthcare providers during the transition period to optimize care for PwCF.

Healthcare access, affordability, and quality: In PwCF, the societal economic burden and impact on individuals’ health-related QoL is exorbitant. Quantifying the economic burden in the US population is difficult due to the variety of insurance options available, with many individuals receiving government-based health insurance while others are on private payer plans. In 2021, the total socioeconomic burden of CF in Canada accounted for $414 million (Canadian dollar). ⁴¹ Of these, direct costs (e.g., hospitalization) accounted for two-thirds of the total costs, with medications comprising all direct costs. Out-of-pocket costs to individuals and caregivers amount of 18.7% of all direct costs. Indirect costs representing absenteeism from work accounted for one-third of the total cost. Hassan and co-workers ⁴¹ examined the impact of exacerbation and healthcare cost from a retrospective data of the Medicaid Multi-State administrative claims database (2010–2014; n = 1196 CF patients) aged 6 years and older with 1 year follow-up. Forty-seven percent of the PwCF had inpatient admission, and 27% had subsequent hospitalizations during the follow-up, totaling 29.1 days per year in hospital. Moreover, healthcare expenditures for PwCF exponentially rose for acute exacerbation events with increasing age: (6–11 years, US $ 44,589 and 12–17 years, US $139, 024), to (18–26 years, US$116, 179 and 27–34 years US$ 387, 752). These data are likely reflective of the experience that individuals in other wealthy nations experience and provide evidence of the high-cost burden of CF disease. In addition, children with CF with acute exacerbations in the US were associated with increased emergency care utilization and hospitalization^42–44 and financial burden due to high-deductible insurance plans, on average, about $500.00 per month, ⁴⁵ including transportation expenses to and from the clinic, which are associated with unmet medical needs and heavily affect those with low income. ⁴⁶

A recent case-control study compared 1555 wait-listed to 1555 never wait-listed PwCF undergoing evaluation for lung transplant ⁴⁷ and assessed health status scores for PwCF. In this study, lower health status scores correlated with poorer health, and increased odds of being in wait list increased by 69%. In addition, individuals with higher socioeconomic barriers received a lung transplant about half as often as those with lower scores at the same level of medical severity. ⁴⁷ Similarly, other studies have previously associated ethnic minority status, low educational attainment, low household income, and residing in disadvantaged communities with higher odds of dying without lung transplantation in the US. ⁴⁸ Likewise, CF patients with Medicaid insurance are twice the odds of higher risk of death while in the waiting list for lung transplant compared to Medicare or private care insurance. ⁴⁹

Food insecurity: Thirty to sixty percent of PwCF experience debt, housing issues and food insecurity compared to the general population in the US.^50,51 The reasons for this disparity are multifactorial, including individuals with CF experiencing significantly increased caloric demands compared to individuals without CF, unstable employment, and nutritional status that is closely tied to impaired lung function. For these reasons, food insecurity is a particularly important domain of social need for PwCF. A recent self-reported survey showed that food insecurity was associated with adverse health outcomes, including lower lung function and increased hospitalizations ⁵² and underweight in both children and adults in PwCF. ⁵³ A qualitative interview that explored the impact of food insecurity in seventeen adults with CF and nine parents of children with CF patents identified five inter-related themes ⁵⁴ : (1) Food insecurity among CF patients and their families is onerous, (2) Financial constraints imposed by CF contribute to greater food insecurity, (3) Federal and state programs provide merely limited food assistance, (4) Shame and stigma engulf conversations around food insecurity discussions with CF care teams, and (5) emphasizing honest assessment of food insecurity screening in clinical settings becomes critical. ⁵⁴ These themes highlight the pervasiveness of food insecurity in the lives of PwCF and their families. Thus, it is important to provide adequate guidance and support, with an urgent need to normalize food insecurity screening and expand food assistance programs for PwCF, especially those from low SES groups.

In summary, we have identified health disparities in patients with cystic fibrosis, such as differences in SES, greater healthcare utilization, impaired QoL, food insecurity, poor social functioning, and higher barriers for lung transplant surgery, predominantly affecting more ethnic minorities compared to Whites in PwCF. These disparities were propelled by SDOH that included race/ethnicity, SES, geographical location exposed to atmospheric pollution, low SES, and poorer neighborhood status as shown in Figure 1.

Figure 1.

The relationship between social determinants of health influence and outcomes for people with cystic fibrosis (PwCF). Factors within the domains of healthcare access, SES, neighborhood and environment, and ethnicity/genetic background play critical roles in shaping health trajectories in PwCF. This figure also demonstrates that these determinants are interconnected, as one disparity often contributes to another in a bidirectional way.

SDOH and diabetes in CF

CFRD is a common complication of CF, and the likelihood of having CFRD increases with age affecting 2% of children, 19% of adolescents, and 40%–50% of adults. ⁵⁵ There is also sufficient evidence that the prevalence and incidence of CFRD is more common in ethnic minorities compared to Caucasians. ⁵⁶ A previous study (n = 40 CFRD versus n = 40 nondiabetic CF) showed that patients with CFRD had higher rates of lung function decline, especially women compared to nondiabetic patients with CF^57,58 and growth failure in height and weight. ⁵⁸ here is limited literature that examines the impact of SDOH on clinical outcomes pertinent to CFRD. CFRD is distinctive from PwCF, but it shares features of both type 1 and type 2 diabetes. For example, similar to type 1 diabetes, CFRD is characterized by impaired insulin release, and thus the primary treatment of CFRD is insulin, although, similar to type 2 diabetes, there is also a component of insulin resistance. In addition, unlike in type 1 or type 2 diabetes, endocrine pancreatic pathology in CFRD is associated with alpha-cell destruction, impaired glucagon release, and results in significant post-prandial hypoglycemia, negatively affecting QoL.^59,60 Furthermore, in the United States, public insurance policies, including Medicaid, often do not cover insulin pumps or Continuous glucose monitoring (CGM) making diabetes management more difficult and cumbersome emotionally. In addition, CF assistance programs commonly do not cover therapies related to CFRD, which increases the financial burden for PwCF.

The available literature indicates that CFRD is associated with increased risk of acute exacerbations, reduced lung function, and impaired QoL, and the severity of SDOH tends to disproportionately affect PwCF who are from ethnic minority backgrounds. The pathophysiology of CFRD is complex, and management is burdensome for PwCF. SDOH exerts a substantial burden on patients with CFRD by impairing their QoL as illustrated in Figure 2.

Figure 2.

A proposed model for the relationship between the pathophysiology of Cystic Fibrosis Related Diabetes (CFRD) and social determinants of health. Further research is needed to investigate the impact of social determinants of health on CFRD outcomes.

Psychosocial factors and mental health: Low SES was implicated with poorer mental health status and poor prognosis in patients with chronic respiratory diseases. A recent systematic review and meta-analysis showed that about 19% adolescents, 27% adults, and 33% caregivers were suffering from depression, and around 26% adolescents, 28% adults, and 38% caregivers were suffering from anxiety, respectively, which may warrant medical intervention. ⁶¹ For example, in the international depression epidemiological study with 4 years follow-up, baseline elevated depression was associated with 60% increased risk of pre-mature mortality in adults PwCF compared to those without depression. ⁶² There has been a recommendation from CF experts and parents’ priorities for mental health screening, appropriate intervention, and psychosocial support services should be part of the routine care for pediatric and adult PwCF.^63,64 A group telehealth intervention, ⁶⁵ 1-hour session weekly for 8 weeks using mindfulness-based cognitive behavioral therapy (MBCT) compared to usual care in adults (n = 66) PwCF with depression and anxiety. MBCT was effective in improving symptoms of depression in the short-term, but the long-term benefits are uncertain. Similar trends were observed for changes in anxiety, but nonsignificant.

Implication of the findings to clinical practice and research

PwCF experience significant barriers related to insurance, increased out-of-pocket expenses, rural communities (e.g., transportation), food insecurity, and income/employment. In addition, potential discriminatory policies by insurance companies that either exclude specialty drugs or place them in prohibitively high copay tiers create additional burdens for PwCF. Therefore, a comprehensive multidisciplinary approach that includes screening and referrals to address SDOH needs as part of routine clinical practice is a worthy endeavor.

A recent expert workshop ⁶⁰ that examined the impact of CFTR, pathophysiology and outcomes (e.g. genetics and nutrition) including SDOH, race and ethnicity on CFRD, highlighted the lack of evidence and proposed priority areas for future research. First, little evidence is available on the incidence and prevalence of macrovascular and microvascular disease in CFRD, with particular emphasis on understanding racial, ethnic, and SDOH contributing to health outcomes and disparities. Second, research should focus on the impact of SDOH, race, and ethnicity on CFRD outcomes. Third, education and training of additional multidisciplinary practitioners familiar with CFRD and integration of these professionals into the CF care team. ⁶⁰

The recent advance development and implementation of highly effective CFTR therapy with ETI significantly impacted lung function, reduced exacerbation rates, hospitalizations, and improved QoL in PwCF.^4,66,67 Despite these significant developments, the efficacy of ETI on insulin secretion and overall glycemic control and CFRD remains inconclusive.^66–69 A recent expert workshop report from the CF foundation identified several key gaps in research on understanding the role of CFTR in the nervous system, with impacts for development of preclinical models and mechanistic investigations. ⁷⁰ One of the recommended research investigations was the impact of ETI on mood (depression) and anxiety, especially after initiation in pediatric CF populations. In addition, patient screening is not suggested to start until the age of 12 years, as per clinical guidelines, and focuses on the caregiver burden beforehand. Whether starting CFTR modulator treatment at younger ages of CF will improve glycemic control and metabolic profiles of CFRD patients remains elusive. In addition, the workshop report recommended prospective studies in large, generalizable populations to determine if changes in mood and anxiety are different compared to common epidemiological trends in PwCF. Other key areas of research identified by the panel include the impact of ETI on neuropsychological and cognitive symptoms, sleep, symptom management, QoL, and self-perception (both in adults and pediatric populations), and improving the study design of large, longitudinal studies with primary mental health outcomes. ⁶⁶ To date, no studies prospectively examined the potential benefits of lifestyle management (exercise, diet, and weight management) in adults with CFRD, either in comparison with cognitive behavioral therapy or drug therapy, both of which remain important areas for future research.

Exercise training has beneficial effects on mental health across a wide range of disease states and has been shown to reduce glycosylated hemoglobin and enhance glycemic control through increased uptake and an enhancement of insulin action in adults with Type 2 Diabetes. ⁷¹ To date, there is little evidence available for treating both depressive symptoms and CFRD in PwCF using nonpharmacological interventions, such as supervised exercise therapy. In addition, the impact of exercise therapy on SDOH, sedentary lifestyle, and social isolation in adult patients with cystic fibrosis is not adequately examined. Thus, well-controlled prospective clinical trials with long-term follow-up are required to improve the psychosocial health of PwCF.

Conclusion

In summary, limited literature exists on the impact of SDOH on healthcare disparities and the management of comorbidities in adult PwCF. CFRD has a significant adverse impact on clinical outcomes and QoL in adult PwCF. In addition, nonpharmacological interventions to treat adults with CFRD are limited. The efficacy of ETI in ameliorating anxiety and depressive symptoms remains inconclusive. Untreated depression and anxiety in adults with CFRD are associated with poor compliance with medical treatment, impaired QoL, and increased healthcare utilization, thus prospective studies are needed with long-term follow-up.