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.

Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 × 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D Trial) in adults with cystic fibrosis

“…As such, the Cystic Fibrosis Foundation recommends annual measurement of serum 25(OH)D concentration [37, 38]. Vitamin D is associated with better skeletal health, lung function, and decreased risk of pulmonary exacerbations, cystic fibrosis-related diabetes, and infections [23, 37, 39, 40, 41]. Bolus vitamin D dosages are often required to increase serum 25(OH)D concentration in patients with CF, as patient adherence to other treatment options is lower [24, 25, 26].…”

Vitamin D for glycemic control following an acute pulmonary exacerbation: A secondary analysis of a multicenter, double-blind, randomized, placebo-controlled trial in adults with cystic fibrosis

“…Adequate calcium absorption may be beneficial to decrease the risk of CFRD due to its ability to stimulate insulin release to the blood and its possible indirect effect on weight loss [17–20]. Further, vitamin D 3 (cholecalciferol) supplementation has been associated with improved insulin secretion and decreased risk for CFRD [21, 22]. Hyperglycemia and insulin resistance can occur after illness, however, prior studies have not examined changes in glycemic control after treatment of a high-dose bolus of vitamin D 3 supplementation following an acute pulmonary exacerbation (APE).…”

“…Adequate calcium absorption may be beneficial to decrease the risk of CFRD due to its ability to stimulate insulin release to the blood and its possible indirect effect on weight loss [24][25][26][27]. Further, in the context of CF, vitamin D 3 (cholecalciferol) supplementation has been associated with improved insulin secretion and decreased risk for CFRD [8,28]. In a systematic review of seven randomized control trials of children with obesity, four trials indicated that vitamin D supplementation had a positive impact on glycemic control as determined by insulin levels, insulin resistance, and fasting blood glucose [29].…”

“…Adequate calcium absorption may be beneficial to decrease the risk of CFRD due to its ability to stimulate insulin release to the blood and its possible indirect effect on weight loss [17][18][19][20]. Further, vitamin D 3 (cholecalciferol) supplementation has been associated with improved insulin secretion and decreased risk for CFRD [21,22].…”

Calcipotriol Attenuates Form Deprivation Myopia Through a Signaling Pathway Parallel to TGF-β2–Induced Increases in Collagen Expression

“…In other multiple organs, low levels of vitamin D3 are instead associated with increases in fibrosis in different pathologic conditions. 22 – 24 On the other hand, transforming growth factor β2 (TGF-β2) promotes the synthesis of COL1A1 in scleral fibroblasts. 25 Declines in TGF-β expression levels are likely associated with decreases in scleral collagen content during myopia development.…”