CF: Nutrition Assessment of Biochemical Values 2020
Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.
CF: Oral Glucose Tolerance Testing (OGTT)
For individuals with cystic fibrosis (CF) ≥10 years of age who have not previously been diagnosed with diabetes, oral glucose tolerance testing (OGTT) is recommended annually or as indicated by glucose levels and clinical signs and symptoms (weight loss, increase in pulmonary exacerbations, and/or loss of lung function) during nutrition assessment, since progression to CFRD is a risk factor for pulmonary decline and mortality.
CF: Fat-Soluble Vitamins
For all individuals with cystic fibrosis (CF), regardless of exocrine pancreatic function, it is reasonable for the RDN or international equivalent to assess fat-soluble vitamin levels at least annually, since there may be high risk of fat-soluble vitamin abnormality due to pancreatic insufficiency and malabsorption.
CF: Lipid Profile
For individuals with cystic fibrosis (CF), it is reasonable for the RDN or international equivalent to evaluate fasting lipid profile at least once between the ages of 10 and 20 years and every 4-6 years thereafter — or more frequently if the individual has multiple risk factors for cardiovascular disease — in order to detect and prevent dyslipidemia.
Risks/Harms of Implementing This Recommendation
Laboratory tests may be associated with discomfort due to needle sticks for OGTT and drawing blood for fat-soluble vitamin levels and lipid profile. Clients may have an aversion to the glucose solution for OGTT. However, this harm is minimal in comparison to the benefit that individuals with cystic fibrosis may experience from early detection of pathological laboratory levels. In addition, some of these labs may already be indicated from the primary care physician and, thus, assessment by the RDN requires no additional harms.
Conditions of Application
Role of the RDN. The RDNs role in recommending assessment of lab values outside of the typical blood panel will vary by facility policies, healthcare team and specific RDN. In some cases, the RDN may recommend assessment of lab measures if a nutrition concern is suspected or in accordance with standard practices to prevent disease progressions (such as regular OGTTs). Correcting abnormal laboratory values will rarely be the sole responsibility of the RDN. RDNs must work within the interdisciplinary team to determine if the abnormal lab value is a priority and, if so, what can be done to correct it that is in the best interest of the specific individual at the specific time.
OGTT. An OGTT is not clinically indicated for individuals already diagnosed with CFRD.
Indications and Frequency for Measuring Fat-soluble Vitamin Levels. It is reasonable for practitioners to adhere to consensus recommendations that are currently utilized in CF practice that fat-soluble vitamin levels should be monitored at least annually (Saxby et al 2017, Turck et al 2016). More frequent assessment may be warranted if the practitioner suspects deficiency or toxicity due to reported or observed signs and symptoms or if fat-soluble vitamin dosing guidelines change. A recent guideline from Australia and New Zealand describes that indications for more frequent assessment of vitamins A, E and K include changes in supplementation dosage or related treatments, CF-related liver disease or history of intestinal resection or malabsorption, poor adherence to PERT or vitamin A supplementation (Saxby et al 2017, Turck et al 2016). Vitamin D levels should be assessed at the end of winter, or season should be accounted for when interpreting vitamin D levels (Saxby et al 2017, Tangpricha et al 2012). Vitamin K levels cannot be measured directly and may instead be assessed using surrogate measures such as Prothrombin Time, though this test may not be high-quality indicator of vitamin K status.
Lipid Profile. Based on guidance for the general pediatric population, it is reasonable to evaluate triglyceride and HDL, LDL and total cholesterol levels at least once between 10 and 20 years, and more frequently as determined by risk assessment. For adults 20 years and older, it is reasonable to screen for dyslipidemia at least every 4-6 years or more frequently for adults with CF who have multiple risk factors for cardiovascular disease (National Center for Chronic Disease Prevention and Health Promotion 2019, American Academy of Pediatrics 2016). Frequency of lipid profile assessment may be increased for individuals with heart disease or diabetes or who have a family history of high cholesterol. The CDC recommends the individual talk to the interdisciplinary healthcare team about how often to monitor blood cholesterol levels (National Center for Chronic Disease Prevention and Health Promotion 2019).
Potential Costs Associated with Application
OGTT tests are low in cost and typically covered by insurance. Lipid profile may be part of the standard blood panel. Any laboratory assay may be expensive and insurance coverage and copays may vary. The RDN should be mindful of a cost-benefit ratio when recommending any laboratory assay. Co-partnering with the individual /family with CF is essential to determine their preferences and concerns.
Oral Glucose Tolerance Test
Background. Endocrine pancreatic insufficiency is a hallmark of disease pathology for many individuals with CF, which may ultimately result in glucose intolerance and CFRD. CFRD is defined by OGTT (Moran et al 2018) and is the most common comorbidity in CF, with approximately 35-50% of individuals affected (Moran et al 2018, Kayani et al 2018). While incidence of CFRD is high for adolescents (Ode et al 2010), management may be particularly challenging due to rapid growth and potential for hurdles with maintaining optimal therapy. Fasting glucose levels alone may not reflect increased risk of CFRD (Frohnert et al 2010). While individuals with CF typically value the benefits of screening for CFRD with the OGTT, annual testing can be challenging, and rates of OGTT completion have traditionally been low (Cystic Fibrosis Foundation Patient Registry 2017). In clinical practice it is can be difficult to motivate adult patients to complete this test annually because of the time commitment, as well as multiple needle sticks and taste aversion to the glucose solution.
Evidence. In the systematic review supporting this guideline, pediatric individuals age 5 -20 years who had CFRD exhibited greater decline in FEV1% predicted after ten or more years of follow-up compared to those who did not have CFRD (Goss et al 2018, Welsh et al 2014). In adults with CF, presence of CFRD was associated with increased decline in FEV1% predicted after a follow up of 5 to up to 13 years and was associated with higher risk of mortality after a follow-up of up to 24 years (Goss et al 2018, Amadori et al 2009, Ramos et al 2017, George et al 2011). Therefore, RDNs should emphasize the importance of early identification and management of CFRD in order to educate individuals on management with nutrition and exercise and to evaluate insulin needs. The recommended frequency for OGTT assessment is based on recommendations from the International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines for Children and Adolescents with CF 2018 (Moran et al 2018) Continuous glucose monitoring systems are not indicated for diagnosis of CFRD, but may be ordered by an endocrinologist and data can be utilized by RDNs to guide nutrition care.
Fat-soluble Vitamin Levels
Due to pancreatic insufficiency and malabsorption, individuals with CF are at high risk of fat-soluble vitamin deficiency (Rana et al 2014). In the systematic review supporting this guideline, there was very limited evidence examining the relationship between fat-soluble vitamin levels and hard outcomes (Academy of Nutrition and Dietetics 2019). However, the health consequences of fat-soluble vitamin deficiencies are well known, including susceptibility to infections, osteomalacia, muscle weakness or pain, neurologic symptoms and impaired clotting (Oregon State University Linus Pauling Institute 2019).
Dyslipidemia is common in individuals with CF related to pancreatic insufficiency, malabsorption, inflammation, imbalanced macronutrient intake and, in some cases, CF-related liver disease (Rhodes et al 2010, Alves et al 2012, Figueroa et al 2002). However, the consequences of these abnormal triglyceride and cholesterol levels on hard outcomes, including FEV1, quality of life and mortality, are unclear due to lack of available evidence (Academy of Nutrition and Dietetics 2019, Ollero et al 2011). This systematic review did not investigate the relationship of plasma lipid levels with cardiovascular disease as an outcome in CF, although in the general population, dyslipidemia is associated with higher risk of cardiovascular morbidities and mortality (Kopin et al 2017). Limited research suggests that pediatric participants (7-18 years) with CF may be at increased risk of endothelial dysfunction (Poore et al 2013) and other cardiovascular risk factors such as increased inflammation and lipid abnormalities (Cross et al 2013). However, evidence is lacking to determine if these risk factors are likely to progress to atherosclerotic plaques (Skolnik et al 2016).
Essential Fatty Acids
Evidence examining the relationship between essential fatty acid levels and hard outcomes in participants with CF and meeeting inclusion criteria for this systematic review was limited (Ollero et al 2011, Maqbool et al 2008). There was no evidence to suggest an optimal frequency of assessing these measures or clear indications for when levels should be measured. Recent nutrition guidelines for CF have described that the effect of essential fatty acid supplementation is unclear (Saxby et al 2017, Turck et al 2016) Thus, the workgroup determined that there was not adequate evidence to inform a specific protocol for assessing essential fatty acid levels.
Recommendation Strength Rationale
The evidence supporting the recommendation for regular OGTT is supported by Grade II (Fair) evidence describing the longitudinal relationship between CFRD and pulmonary decline and mortality. The only evidence available for fat-soluble vitamins was for vitamin D levels, and this was based on Grade III (weak/limited) evidence. The evidence describing the relationship between lipid profile and FEV1 was Grade III (weak/limited).
- Risks/Harms of Implementing This Recommendation
The recommendations were created from the evidence analysis on the following questions. To see detail of the evidence analysis, click the blue hyperlinks below (recommendations rated consensus will not have supporting evidence linked).
In pediatric participants with CF, what is the longitudinal relationship (at least 3 months) between vitamin D levels and FEV1?
In pediatric participants with CF, what is the longitudinal relationship (at least 3 months) between cystic fibrosis-related diabetes (CFRD) and FEV1?
In pediatric participants with CF, what is the longitudinal relationship (at least 3 months) between cystic fibrosis-related diabetes (CFRD) and Quality of Life or Mortality?
In adults with CF, what is the longitudinal relationship (at least 3 months) between cystic fibrosis-related diabetes (CFRD) and FEV1 or mortality?
In adults with CF, what is the longitudinal relationship (at least 3 months) between cystic fibrosis-related diabetes (CFRD) and QoL?
In participants with CF, what is the longitudinal relationship (at least 3 months) between essential fatty acid (EFA) deficiencies and FEV1?
In participants with CF, what is the longitudinal relationship (at least 3 months) between micronutrient deficiencies (vitamins A, D, E and zinc) and hard outcomes (FEV1, Quality of Life or mortality)?
In participants with CF, what is the longitudinal relationship (at least 3 months) between essential fatty acid (EFA) deficiencies and QoL or mortality?
In participants with CF, what is the longitudinal relationship (at least 3 months) between lipid profile and FEV1?
In participants with CF, what is the longitudinal relationship (at least 3 months) between lipid profile and QoL or mortality?
In pediatric and adults with CF combined, what is the longitudinal relationship (at least 3 months) between CFRD and mortality?
McCauley L, Thomas W, Laguna T, Regelmann W, Moran A, Polgreen L. Vitamin D deficiency is associated with pulmonary exacerbations in children with cystic fibrosis. Annals of the American Thoracic Society 2014; 11:198-204
Goss C, Sykes J, Stanojevic S, Marshall B, Petren K, Ostrenga J, Fink A, Elbert A, Quon B, Stephenson A. Comparison of nutrition and lung function outcomes in [atients with cystic fibrosis living in Canada and the United States. American Journal of Respiratory and Critical Care Medicine 2018; 197:768-775
Welsh L, Robertson C, Ranganathan S. Increased rate of lung function decline in Australian adolescents with cystic fibrosis. Pediatric Pulmonology 2014; 49:873-7
Amadori A, Antonelli A, Balteri I, Schreiber A, Bugiani M, De Rose V. Recurrent exacerbations affect FEV(1) decline in adult patients with cystic fibrosis. Respiratory Medicine 2009; 103:407-13
George P, Banya W, Pareek N, Bilton D, Cullinan P, Hodson M, Simmonds N. Improved survival at low lung function in cystic fibrosis: cohort study from 1990 to 2007. BMJ (Clinical research ed.) 2011; 342:d1008
Ramos K, Quon B, Heltshe S, Mayer-Hamblett N, Lease E, Aitken M, Weiss N, Goss C. Heterogeneity in survival in adult patients with cystic fibrosis with FEV < 30% of predicted in the United States. Chest 2017; 151:1320-1328
Maqbool A, Schall J, Garcia-Espana J, Zemel B, Strandvik B, Stallings V. Serum linoleic acid status as a clinical indicator of essential fatty acid status in children with cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 2008; 47:635-44
Ollero M, Astarita G, Guerrera I, Sermet-Gaudelus I, Trudel S, Piomelli D, Edelman A. Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients. Journal of Lipid Research 2011; 52:1011-22
Chamnan P, Shine B, Haworth C, Bilton D, Adler A. Diabetes as a determinant of mortality in cystic fibrosis. Diabetes Care 2010; 33:311-6
Hofer M, Schmid C, Benden C, Speich R, Inci I, Weder W, Boehler A. Diabetes mellitus and survival in cystic fibrosis patients after lung transplantation. Journal of Cystic Fibrosis 2012; 11:131-6
Vieni G, Faraci S, Collura M, Lombardo M, Traverso G, Cristadoro S, Termini L, Lucanto M, Furnari M, Trimarchi G, Triglia M, Costa S, Pellegrino S, Magazzù G. Stunting is an independent predictor of mortality in patients with cystic fibrosis. Clinical Nutrition (Edinburgh, Scotland) 2013; 32:382-5
References not graded in Academy of Nutrition and Dietetics Evidence Analysis Process
- Academy of Nutrition and Dietetics Evidence Analysis Library. In individuals with CF, what is the relationship between nutrition parameters and hard outcomes? Evidence Analysis Library Cystic Fibrosis Systematic Review web site. https://www.andeal.org/topic.cfm?menu=5876&cat=5979. Published 2019. Accessed September 25, 2019.
- Alves C, Lima D, Cardeal M, Santana A. Dyslipidemia in racially admixtured children with cystic fibrosis. Indian J Endocrinol Metab. 2012;16(4):585-588.
- American Academy of Pediatrics. 2016 Recommendations for Preventive Pediatric Health Care. Pediatrics. 2016;137.
- Cross CE, Reverri EJ, Morrissey BM. Joining the crowd: cystic fibrosis and cardiovascular disease risk factors. Chest. 2013;143(4):882-884.
- Cystic Fibrosis Foundation Patient Registry. 2017 Annual Data Report. Available at: https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2017-Patient-Registry-Annual-Data-Report.pdf. Accessed October 15, 2019.
- Figueroa V, Milla C, Parks EJ, Schwarzenberg SJ, Moran A. Abnormal lipid concentrations in cystic fibrosis. Am J Clin Nutr. 2002;75(6):1005-1011.
- Frohnert BI, Ode KL, Moran A, et al. Impaired fasting glucose in cystic fibrosis. Diabetes Care. 2010;33(12):2660-2664.
- Kayani K, Mohammed R, Mohiaddin H. Cystic fibrosis-related diabetes. Front Endocrinol. 2018;9(101555782):20.
- Kopin L, Lowenstein C. Dyslipidemia. Ann Intern Med. 2017;167(11):Itc81-itc96.
- Oregon State University Linus Pauling Institute. Micronutrient Information Center. Oregon State Universiy. https://lpi.oregonstate.edu/mic. Published 2019. Accessed December 2, 2019.
- Moran A, Pillay K, Becker D, Granados A, Hameed S, Acerini CL. ISPAD Clinical Practice Consensus Guidelines 2018: Management of cystic fibrosis-related diabetes in children and adolescents. Pediatr Diabetes. 2018;19 Suppl 27:64-74.
- National Center for Chronic Disease Prevention and Health Promotion. Getting Your Cholesterol Checked. U.S. Department of Health and Human Services. https://www.cdc.gov/cholesterol/cholesterol_screening.htm. Published 2019. Accessed September 2019.
- Ode KL, Frohnert B, Laguna T, et al. Oral glucose tolerance testing in children with cystic fibrosis. Pediatric diabetes. 2010;11(7):487-492.
- Poore S, Berry B, Eidson D, McKie KT, Harris RA. Evidence of vascular endothelial dysfunction in young patients with cystic fibrosis. Chest. 2013;143(4):939-945.
- Rana M, Wong-See D, Katz T, et al. Fat-soluble vitamin deficiency in children and adolescents with cystic fibrosis. J Clin Pathol. 2014;67(7):605-608.
- Rhodes B, Nash EF, Tullis E, et al. Prevalence of dyslipidemia in adults with cystic fibrosis. J Cystic Fibros. 2010;9(1):24-28.
- Saxby N. PC, Kench A., King S., Crowder T., van der Haak N. and the Australian and New Zealand Cystic Fibrosis Nutrition Guideline Authorship Group. Nutrition Guidelines for Cystic Fibrosis in Australia and New Zealand. In. Sydney: Thoracic Society of Australia and New Zealand; 2017.
- Skolnik K, Levy RD, Wilcox PG, Quon BS. Coronary artery disease in cystic fibrosis: An emerging concern? J Cyst Fibros. 2016;15(6):e70-e71.
- Tangpricha V, Kelly A, Stephenson A, et al. An update on the screening, diagnosis, management, and treatment of vitamin D deficiency in individuals with cystic fibrosis: evidence-based recommendations from the Cystic Fibrosis Foundation. J Clin Endocrinol Metabolism. 2012;97(4):1082-1093.
- Turck D, Braegger CP, Colombo C, et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin Nutrition (Edinburgh, Scotland). 2016;35(3):557-577.