Vitamin D Status and Risk of Cystic Fibrosis-Related Diabetes: A Retrospective Single Center Cohort Study

Abstract

Objective: Cystic fibrosis-related diabetes (CFRD) affects up to half of the people with cystic fibrosis (CF) by adulthood. CFRD is primarily caused by pancreatic dysfunction that leads to insufficient insulin release and/or insulin resistance. Exocrine pancreatic insufficiency in people with CF is associated with fat-soluble vitamin malabsorption, including vitamins A, D, E, and K. This study examined the relationship between vitamin D status, assessed by serum 25-hydroxyvitamin D (25(OH)D), and the development of CF-related diabetes (CFRD) in adults with CF. Methods: This was a retrospective cohort study of adults seen at a single CF center. The data were extracted from the electronic medical records and the Emory Clinical Data Warehouse, a data repository of health information from patients seen at Emory Healthcare. We collected age, race, the first recorded serum 25-hydroxyvitamin D (25(OH)D) concentration, body mass index (BMI), and onset of diabetes diagnosis. Log-rank (Mantel–Cox) tests were used to compare the relative risk of CFRD onset in the subjects with stratified vitamin D status and weight status. A sub-group analysis using chi-square tests assessed the independence between vitamin D deficiency and CFRD risk factors, including gender and CF mutation types (homozygous or heterozygous for F508del, or others). Unpaired t-tests were also used to compare the BMI values and serum 25(OH)D between the CF adults based on the CFRD development. Results: This study included 253 subjects with a mean age of 27.1 years (±9.0), a mean follow-up time period of 1917.1 (±1394.5) days, and a mean serum 25(OH)D concentration of 31.8 ng/mL (±14.0). The majority (52.6%) of the subjects developed CFRD during the study period. Vitamin D deficiency (defined as 25(OH)D < 20 ng/mL) was present in 25.3% of the subjects. Close to two thirds (64.1%) of the subjects with vitamin D deficiency developed CFRD during the study. Vitamin D deficiency increased the risk of developing CFRD (chi-square, p = 0.03) during the course of the study. The time to the onset of CFRD stratified by vitamin D status was also significant (25(OH)D < 20 ng/mL vs. 25(OH)D ≥ 20 ng/mL) (95% CI: 1.2, 2.7, p < 0.0078). Conclusion: Our findings support the hypothesis that adults with CF and vitamin D deficiency are at a higher risk of developing CFRD and are at risk for earlier CFRD onset. The maintenance of a serum 25(OH)D concentration above 20 ng/mL may decrease the risk of progression to CFRD.