Acute soluble fibre supplementation has no impact on reducing post-prandial glucose excursions in adults with cystic fibrosis and glucose intolerance.

BACKGROUND: Cystic fibrosis (CF)-related diabetes (CFRD) is a common comorbidity in CF. In CFRD, fasting blood glucose level is often normal, but post-prandial glycaemia (PPG) is problematic. Elevated PPG has been associated to a higher risk of developing CFRD, a worst clinical state and a lower pulmonary function. Interventional studies in type 2 diabetes have demonstrated a beneficial impact of fibre supplement on PPG. METHODS: Our objective is to evaluate the efficiency of 2 doses of a soluble fibre supplement to lower PPG in CF patients with glucose intolerance (pre-diabetic or CFRD patients). This is a double-blinded crossover interventional study with three interventions: placebo or psyllium fibre (5.1g or 7.7g) of soluble fibre consumed before breakfast. A second meal (lunch) is also eaten four hours later to evaluate a second meal effect. Blood glucose and insulin were measured during the interventions. RESULTS: In 14 adult CF patients with impaired glucose tolerance (IGT; n=10) or CFRD (n=4), we observed no beneficial effect of fibre supplementation on PPG for both meals. However, all blood glucose levels were lower after the lunch compared to breakfast in spite of the higher carbohydrate content. CONCLUSION: An acute treatment with fibre supplementation had no effect on blood glucose control in patients with CF-IGT or CFRD.

Low vitamin K status in adults with cystic fibrosis is associated with reduced body mass index, insulin secretion, and increased pseudomonal colonization.

Patients with cystic fibrosis (CF) are at high risk of fat-soluble vitamin deficiencies, even with supplementation. The contribution of a suboptimal vitamin K status to respiratory and endocrine pathophysiology in CF has been inadequately characterized. This is a cross-sectional study in adult CF patients (≥18 years old) from the Montreal Cystic Fibrosis Cohort. Vitamin K1 (VK1) was measured with high-performance liquid chromatography, using fasted serum samples collected during an oral glucose tolerance test (OGTT: 2 h with plasma glucose and insulin every 30 min) (n = 168). Patients were categorized according to VK1 status (suboptimal defined as <0.30 nmol/L). Suboptimal VK1 levels were observed in 66% of patients. Patients with a suboptimal VK1 status have a higher risk of colonization with Pseudomonas aeruginosa (p = 0.001), have lower body mass index (BMI) (p = 0.003), and were more likely to have exocrine pancreatic insufficiency (p = 0.002). Using an established threshold for VK1, we did show significantly reduced OGTT-derived measures of insulin secretion in patients with a VK1 status below 0.30 nmol/L (first- and second-phase area under the curve (AUC)INS/GLU (p = 0.002 and p = 0.006), AUCINS (p = 0.012) and AUCINS/GLU (p = 0.004)). Subclinical vitamin K deficiency is more common than other fat-soluble vitamin deficiencies in patients with CF. We demonstrate an association between a suboptimal VK1 status and measures of insulin secretion. We highlight the potential associations of mild vitamin K deficiency with pseudomonal colonization and lower BMI, although these need to be validated in prospective studies.

Influence of pre-diabetic and pancreatic exocrine states on pulmonary and nutritional status in adults with Cystic Fibrosis.

BACKGROUND: In 1992, a landmark study demonstrated clinical deterioration in respiratory function and nutritional status prior to the onset of cystic fibrosis-related diabetes (CFRD). We re-evaluated this outcome. METHODS: The Montreal Cystic Fibrosis Cohort is a prospective CFRD screening study. We performed a 6-year retrospective analysis of nutritional parameters and FEV1 (%) in subjects who developed incident CFRD and in controls who maintained normoglycemia (NG). In the former group, data was collected over 6 years prior to diabetes onset. RESULTS: Subjects (n = 86) had a mean age of 31.7 ± 8.1 years, BMI of 23.0 ± 4.0 kg/m2, and FEV1% of 70.1 ± 24.2%. Eighty-one percent had pancreatic insufficiency (PI). Patients were grouped as follows: NG+PS (pancreatic sufficient) (n = 16), NG+PI (pancreatic insufficient) (n = 21), CFRD+PS (n = 3) and CFRD+PI (n = 46). At their most recent screen NG+PS subjects had significantly greater BMI, as compared to NG+PI and CFRD+PI groups (26.2 ± 3.6 kg/m2 vs 22.6 ± 4.2 kg/m2 vs 22.1 ± 3.5 kg/m2, p = 0.0016). FEV1 was significantly greater in the NG+PS group (91.5 ± 16.8% vs 67.8 ± 25.3% vs 63.5 ± 22.2%, p = 0.0002). The rates of change in weight, BMI, fat mass (%), and FEV1 prior to the most recent visit (NG+PS, NG+PI groups) or to the diagnosis of de novo CFRD were similar between groups. CONCLUSION: In a contemporary context, CFRD onset is not preceded by deterioration in BMI, fat mass, or pulmonary function. Low BMI and FEV1 are more closely associated with PI than a pre-diabetic state.

Overweight, obesity and significant weight gain in adult patients with cystic fibrosis association with lung function and cardiometabolic risk factors.

BACKGROUND: For patients with cystic fibrosis (CF), maintaining a normal BMI is associated with better pulmonary function (FEV1) and survival. Given therapy improvements, some patients are now overweight, obese or present rapid weight gain. However, the impact of being overweight on clinical outcomes (e.g. FEV1 & metabolic complications) remains unknown. METHODS: Baseline data from 290 adult CF patients and observational follow-up (3.5 years; n = 158) were collected. BMI categories: underweight (UW < 18.5 kg/m2), normal (NW 18.5-26.9 kg/m2), and overweight/obese (OW ≥ 27 kg/m2). Follow-up data (weight change over time): weight loss (WL>10%), stable (WS), and weight gain (WG>10%). BMI categories and follow-up data were compared to FEV1 and cardiometabolic parameters: glucose tolerance, estimated insulin resistance (IR), blood pressure (BP), and lipid profile. RESULTS: For BMI categories, 35 patients (12.1%) were UW, 235 (81.0%) NW, and 20 (6.9%) OW. Compared to UW and NW patients, OW patients are older (p < 0.001), had less pancreatic insufficiency (p = 0.009), a higher systolic BP (p = 0.004), higher LDL (p < 0.001), and higher IR (p < 0.001). Compared to UW patients, OW patients had a better FEV1 (p < 0.001). For weight change, WL was observed in 7 patients (4.4%), WS in 134 (84.8%) and WG in 17 patients (10.8%). Compared to WL and WS patients, WG patients had a 5% increase in FEV1 accompanied by higher IR (p = 0.017) and triglycerides (p < 0.001). No differences were observed for glucose tolerance for neither BMI nor weight change. CONCLUSION: A higher weight or weight gain over time are associated with a better FEV1 but also some unfavorable cardiometabolic trends.

Vitamin D3 supplementation among adult patients with cystic fibrosis.

BACKGROUND & AIMS: Vitamin D (Vit D) deficiency in cystic fibrosis (CF) is partially secondary to exocrine pancreatic insufficiency. Our aim was to establish a Vit D3 supplementation protocol that will increase 25(OH)D to the recommended level (30 ng/mL). METHODS: Retrospective study of 200 patients (≥18 years) conducted from February 2007 to June 2014 at the CF clinic of the Centre Hospitalier de l'Université de Montréal. Vit D3 supplementation protocol was 1600 IU/day or 10,000 IU/week during the summer (May 1st to October 31st) and 3200 IU/day or 20,000 IU/week during the winter (November 1st to April 30th), in addition to the 1200 IU/day included in multivitamins. RESULTS: Significant increase in serum 25(OH)D levels from baseline (25.9 ± 10.3 ng/mL) to follow-up (37.0 ± 11.4 ng/mL) (P ≤ 0.001). At follow-up, increased doses during the winter improved serum 25(OH)D levels to a degree comparable to the summer. CONCLUSIONS: This supplementation protocol is efficient and needs to be tested in other CF adult cohorts and correlated to potential health benefit measurements.

Plasma zinc in adults with cystic fibrosis: correlations with clinical outcomes.

BACKGROUND: Zinc status has been previously documented in cystic fibrosis (CF) infants, children and adolescents. However, despite the increasing life expectancy observed in CF populations, data regarding zinc status of CF adults are surprisingly lacking. The objectives of this study were to (1) characterize zinc status and (2) explore associations between zinc status and clinical outcomes of CF adult patients. METHODS: A retrospective chart review was performed for patients who had their plasma zinc measured between 2009 and 2012. Data included demographics, clinical characteristics, biochemical parameters and co-morbid conditions. RESULTS: A total of 304 CF patients were included in the study. These patients displayed a good nutritional status (mean BMI±SD: 22.7±3.5) and moderate lung disease (mean FEV1±SD: 66.3±22.2). Low plasma zinc concentration (<9.2µmol/L) was found in 68 out of 304 CF patients (22.4%). Compared to patients with normal zinc, those with low zinc had significantly lower forced vital capacity and forced expiratory volume in one second. 72% of CF adults with low zinc suffered from bone disease (vs 49% with normal zinc, p=0.037) and 79% had impaired glycemic status (vs 58%, p=0.016). Accordingly, negative correlations were found between plasma zinc and glucose (r=-0.139, p=0.0001), HbA1c (r=-0.237, p=0.0001) and fructosamine (r=-0.134, p=0.034). In multiple linear regression, albumin and glycemic status were significant predictors of plasma zinc. CONCLUSION: Our data indicated that nearly one quarter of CF adults with good nutritional status and moderate lung disease had low plasma zinc concentration and that low zinc status was associated with worse clinical outcomes.