Clinical Care Guidelines for Cystic Fibrosis–Related Diabetes

ystic fibrosis-related diabetes (CFRD) is the most common comorbidity in people with cystic fibrosis (CF), occurring in ϳ20% of adolescents and 40 -50% of adults (1).While it shares features of type 1 and type 2 diabetes, CFRD is a distinct clinical entity.It is primarily caused by insulin insufficiency, although fluctuating levels of insulin resistance related to acute and chronic illness also play a role.The additional diagnosis of CFRD has a negative impact on pulmonary function and survival in CF, and this risk disproportionately affects women (2-4).In contrast to patients with other types of diabetes, there are no documented cases of death from atherosclerotic vascular disease in patients with CFRD, despite the fact that some now live into their sixth and seventh decades.These guidelines are the result of a joint effort between the Cystic Fibrosis Foundation (CFF), the American Diabetes Association (ADA), and the Pediatric Endocrine Society (PES).They are intended for use by CF patients, their care partners, and health care professionals and include recommendations for screening, diagnosis, and medical management of CFRD.This report focuses on aspects of care unique to CFRD.A comprehensive summary of recommendations for all people with diabetes can be found in the ADA Standards of Medical Care, published annually in the January supplement to Diabetes Care (5).METHODS -In 2009, CFF in collaboration with ADA and PES convened a committee of CF and diabetes experts to update clinical care guidelines for CFRD.Investigators at Johns Hopkins University conducted evidence reviews on relevant clinical questions identified by the guidelines committee.The reviews were provided to the committee to use in developing recommendations.Where possible, the evidence for each recommendation was considered and graded by the committee using the ADA (5) and the U.S. Preventive Services Task Force (USP-STF) (6) grading systems (Table 1).Recommendations from existing published guidelines were used when available and appropriate, and these are indicated as consensus statements.The committee also made consensus recommendations for topics not included in the evidence reviews or for which limited evidence was available in the literature.Recommendations will be updated as warranted by new evidence, and the guidelines will be reviewed 3 years after release date to determine if an update is needed.A summary of the committee’s recommendations is presented in Table 2.SCREENING -CFRD is often clinically silent.In other populations, the primary consequences of unrecognized diabetes are macrovascular and microvascular disease.In CF, the nutritional and pulmonary consequences of diabetes are of greater concern.CFRD is associated with weight loss, protein catabolism, lung function decline, and increased mortality (2,3,7-17), and thus regular screening is warranted. Screening tests for CFRDAlthough hemoglobin A1C (A1C) may become the standard screening test for type 2 diabetes (5), the committee concluded that it is not sufficiently sensitive for diagnosis of CFRD and thus should not be used as a screening test.Eight studies were identified that assessed A1C as a screening test in this population (7,18 -24).The authors of one prospective cohort study of 62 participants with CF and 107 healthy control subjects reported that A1C levels were higher in the CF group than among the control subjects, leading them to suggest that the use of A1C was appropriate (18).However, six studies (including two prospective cohort studies [7,21], two cross-sectional studies [19,20], one case-control study [23], and one case series [22[) with a total of 477 participants demonstrated low degrees of correlation between A1C and glucose tolerance status (7,19 -23).Additionally, a cross-sectional study of 191 participants