Prevalence of hypoglycemia during oral glucose tolerance testing in adults with cystic fibrosis and risk of developing cystic fibrosis-related diabetes.

BACKGROUND: Hypoglycemia in cystic fibrosis (CF) patients during the oral glucose tolerance test (OGTT) has been reported; however, these patients have not been well-characterized. Few studies have examined whether hypoglycemia during the OGTT increases the risk of developing CF-related diabetes (CFRD). Objectives of this study were to describe the characteristics of CF patients with hypoglycemia during the OGTT and to determine the incidence and time to development of CFRD in those with hypoglycemia. METHODS: This cohort study included 466 adults with CF at the Toronto Adult CF Clinic between 1996 and 2015. Subjects were classified into two groups based on their plasma glucose (PG) level 2 h after a 75 g OGTT: hypoglycemia (PG ≤ 3.9 mmol/L) or no hypoglycemia (PG > 3.9 mmol/L). Clinical and demographic data were collected from the clinic visit closest to the OGTT. Differences between groups were assessed using Fisher's exact test or Mann-Whitney-Wilcoxon test. RESULTS: 138 patients (29.6%) experienced hypoglycemia during the OGTT. More males experienced hypoglycemia compared to no hypoglycemia (69.6% vs. 54.6% respectively; p = 0.003). Those who were heterozygous deltaF508 were more likely to experience hypoglycemia (p = 0.006). Subjects who experienced hypoglycemia were less likely to develop CFRD at ten years compared to no hypoglycemia (12.0% vs. 42.1%, respectively; p < 0.001). CONCLUSIONS: Hypoglycemia following OGTT is common in CF however the 10 year risk of developing CFRD in these patients was low. Males and those who were heterozygous deltaF508 were at higher risk for hypoglycemia.

Cholecalciferol significantly increases 25-hydroxyvitamin D concentrations in adults with cystic fibrosis.

BACKGROUND: Vitamin D deficiency is increasingly being recognized and treated in patients with cystic fibrosis, although the treatment guidelines are not proven and the effectiveness of vitamin D preparations is untested. OBJECTIVES: The aims of this study were to determine the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency in a large cohort of adults with cystic fibrosis and to evaluate the effectiveness of supplementation with cholecalciferol. DESIGN: In this retrospective cohort design, baseline 25(OH)D concentrations were measured, and the effects of clinical interventions that involved either counseling on compliance or increasing supplemental cholecalciferol on serum 25(OH)D concentrations in those subjects with baseline concentrations

Increased vitamin A and E levels in adult cystic fibrosis patients after lung transplantation.

Most patients with cystic fibrosis (CF) and pancreatic insufficiency require supplementation with fat-soluble vitamins to maintain normal serum levels. Even with supplementation, toxicity is rare. We evaluated serum vitamin A and E levels in 23 adult patients with CF who underwent double lung transplantation. Twenty-one of the subjects were pancreatic insufficient. Fifteen subjects had serum vitamin levels before and after transplant. The median time posttransplantation for these subjects was 9 months. Mean serum vitamin A and E levels were significantly higher posttransplantation (P<0.0001, P<0.001, respectively). Eight subjects who only had posttransplant vitamin levels also had abnormally high vitamin A levels. Although the etiology of this novel finding is unclear, possibilities include altered absorption, drug interactions, impaired retinol metabolism, or increased hepatic synthesis of retinol binding protein.

Longitudinal trends in nutritional status and the relation between lung function and BMI in cystic fibrosis: a population-based cohort study.

BACKGROUND: A high-calorie diet has been a standard of care in cystic fibrosis (CF) for >3 decades. However, energy requirements may have changed with new treatments and milder genotypes. OBJECTIVES: The objectives of this study were to describe longitudinal trends in nutritional status and to evaluate the relation between nutritional status and lung function. DESIGN: This longitudinal cohort study included 909 individuals followed at the Adult CF Clinic in Toronto from 1985 to 2011. Nutritional status was classified on the basis of WHO BMI guidelines. Multivariable linear regression with the use of generalized estimating equations was applied to evaluate the relation between BMI and lung function. RESULTS: The proportion of underweight individuals decreased from 20.6% before 1990 to 11.1% in the most recent decade, whereas the proportion of overweight and obese subjects increased from 7.0% to 18.4% (P < 0.001). Overweight and obese subjects were older, had better lung function, had milder genotypes, and were more often male and pancreatic sufficient. Multivariable regression analyses showed that within the underweight group, an increase in BMI resulted in improved lung function, whereas this effect was half of that in overweight individuals. The greatest advantage of improved nutrition on lung function was observed in the underweight group and in pancreatic- insufficient patients. CONCLUSIONS: Modification to a high-fat diet may be required in some individuals with CF to optimize nutritional health. Higher BMI is associated with improvements in lung function, although the lung function benefit of increasing one's BMI (in kg/m(2)) to >25 is small and needs to be balanced against the known health risks of obesity.

Increased serum vitamin A and E levels after lung transplantation.

BACKGROUND: Adult cystic fibrosis (CF) patients experience significant increases in serum vitamin A and E levels after lung transplantation. It is unclear whether this finding is specific to the CF population or inherent to the lung transplantation process. METHODS: The objectives of this study were to assess pre- and postlung transplantation serum vitamin A and E levels in subjects with end-stage lung disease secondary to all causes. The study population consisted of adults who received a lung transplant at the Toronto Lung Transplant Program between 2004 and 2009. The mean change in serum vitamin A and E levels pre- and postlung transplant was evaluated using a paired t test, while differences in vitamin A and E levels between CF and non-CF subjects were determined using a Student's t test. RESULTS: Thirty-two CF and 21 non-CF subjects who underwent lung transplantation were included in the study. Mean serum vitamin A and vitamin E levels increased significantly after transplant, from 1.2 to 3.5 µmol/L (P<0.0001) and from 21.9 to 33.2 µmol/L (P<0.0001), respectively. The proportion of individuals with serum levels above the upper limit of normal increased from 7.6% to 88.7% (P<0.0001) and from 11.3% to 24.5% (P=0.02) for vitamin A and vitamin E, respectively. The dosage of vitamin supplementation did not increase after transplant. CONCLUSIONS: Significant increases in serum vitamin A and E levels were seen in both CF and non-CF subjects after lung transplantation. Further research is needed to understand the cause and clinical implications of these findings.