20 years of the Montreal Cystic Fibrosis Related Diabetes Screening Cohort: key insights.

Introduction: The Montreal Cystic Fibrosis Related Diabetes Screening Cohort (MCFC) was established in 2004 to study the prevalence, risk factors and management of cystic fibrosis-related diabetes, a significant extrapulmonary complication of cystic fibrosis with an increasing prevalence due to improved cystic fibrosis survival rates. The aims of this review are to highlight the key insights gained from monitoring the MCFC over 20 years, and to discuss the challenges and advantages of establishing such a cohort in a rare disease like cystic fibrosis.

Methods: Adult people with cystic fibrosis were recruited from 2004 onward in Montreal, Canada, excluding those already diagnosed with cystic fibrosis-related diabetes.

The effect of a pre-meal snack and/or postprandial exercise on breakfast glycemic excursion in adults with cystic fibrosis: A pilot study.

Background & Aims: Cystic fibrosis (CF)-related diabetes (CFRD), a common comorbidity in CF, is often preceded and characterized with elevated postprandial glycemic (PPG) excursions. In the general population, the consumption of a pre-meal protein snack and/or physical activity (PA) hinder the elevation of PPG levels. Our objective is to evaluate the effect of a pre-meal snack and/or post-meal PA on PPG excursions in CF.

Cystic fibrosis-related diabetes develops from a combination of insulin secretion defects and insulin resistance.

Aim: The relative contributions of insulin secretory defects and possible additional contribution of insulin resistance for the development of cystic fibrosis (CF)-related diabetes (CFRD) are poorly understood. We aimed to (a) determine which indices of insulin resistance predict progression to CFRD, and (b) to model the relative contributions of insulin secretory function and insulin resistance to predict the risk of CFRD.

Materials And Methods: Three hundred and three individuals living with CF underwent a 2-h oral glucose tolerance test with blood sampling every 30 min at 12-24-month intervals until they developed CFRD or until the end of follow-up (up to 15 years).

Feasibility and accuracy of at-home glucose tolerance tests for cystic fibrosis related diabetes screening.

Background: Adult people living with Cystic Fibrosis (CF) undergo annual screening for CF-related diabetes. These tests represent a burden and can lead to undesirable effects resulting in low adherence. The objectives of this study were to 1) compare gold-standard in-hospital oral glucose tolerance testing (OGTT) with at-home options, and 2) evaluate acceptability of at-home options.

A glycosylated hemoglobin A1c above 6% (42 mmol/mol) is associated with a high risk of developing Cystic Fibrosis-Related Diabetes and a lower probability of weight gain in both adults and children with Cystic Fibrosis.

Objectives: The classical glycosylated hemoglobin A1c threshold of 6.5% is an insensitive screening test for cystic fibrosis-related diabetes (CFRD). We sought to identify CF-specific A1C thresholds associated with 1) risk of progression to CFRD and 2) changes in body mass index (BMI) and forced expiratory volume (FEV1).

Canadian Cystic Fibrosis-related Diabetes Clinical Practice Survey: Analysis of Current Practices and Gaps in Clinical Care.

Objectives: Our aim in this study was to identify challenges and gaps in Canadian practices in screening, diagnosis, and treatment of cystic fibrosis-related diabetes (CFRD), with the goal of informing a Canadian-specific guideline for CFRD.

Methods: We conducted an online survey of health-care professionals (97 physicians and 44 allied health professionals) who care for people living with CF (pwCF) and/or CFRD (pwCFRD).

Results: Most pediatric centres followed <10 pwCFRD and adult centres followed >10 pwCFRD.

Cystic Fibrosis-Related Diabetes: Clinical approach and knowledge gaps.

Cystic Fibrosis-Related Diabetes (CFRD) is a unique type of diabetes mellitus that shares some features with both type 1 and type 2 diabetes. Yet, its distinguishing feature of acute pulmonary complications associated with hyperglycemia and the catabolic metabolism associated with a relative insulin deficiency poses challenges to the application of traditional definitions and treatments for diabetes mellitus. People with CF (pwCF) undergo rigorous annual screening starting at age 10, a process that is challenging for patients and limited by sensitivity, specificity, and reproducibility.

Beyond borders: cystic fibrosis survival between Australia, Canada, France and New Zealand.

Background: Life expectancy for people with cystic fibrosis (CF) varies considerably both within and between countries. The objective of this study was to compare survival among countries with single-payer healthcare systems while accounting for markers of disease severity.

Methods: This cohort study used data from established national CF registries in Australia, Canada, France and New Zealand from 2015 to 2019.

Impact of a high emergency lung transplantation programme for cystic fibrosis in France: insight from a comparison with Canada.

Background: France implemented a high emergency lung transplantation (HELT) programme nationally in 2007. A similar programme does not exist in Canada. The objectives of our study were to compare health outcomes within France as well as between Canada and France before and after the HELT programme in a population with cystic fibrosis (CF).

Real-world use of ivacaftor in Canada: A retrospective analysis using the Canadian Cystic Fibrosis Registry.

Background: Ivacaftor is a CFTR potentiator with demonstrated efficacy in clinical trials and has been rapidly adopted within the CF community. Given the uptake of ivacaftor in eligible people, identifying a comparator group not on modulators to measure effectiveness is difficult. We evaluated health outcomes in individuals with G551D and non-G551D genotypes on ivacaftor using real-world longitudinal data.

YKL-40 as a clinical biomarker in adult patients with CF: Implications of a CHI3L1 single nucleotide polymorphism in disease severity.

Background: YKL-40 (chitinase 3-like 1 gene; CHI3L1) is an inflammatory marker that is increased in the blood of patients with inflammatory diseases, including cystic fibrosis (CF). The objective of our study was to explore the relationship between circulating levels of YKL-40, selected CHI3L1 single nucleotide polymorphisms (SNPs) and the severity of CF disease.

Methods: A prospective cohort of 188 adult patients with CF was established in 2015.

Identification of therapeutics that target eEF1A2 and upregulate utrophin A translation in dystrophic muscles.

Up-regulation of utrophin in muscles represents a promising therapeutic strategy for the treatment of Duchenne Muscular Dystrophy. We previously demonstrated that eEF1A2 associates with the 5'UTR of utrophin A to promote IRES-dependent translation. Here, we examine whether eEF1A2 directly regulates utrophin A expression and identify via an ELISA-based high-throughput screen, FDA-approved drugs that upregulate both eEF1A2 and utrophin A.

Omalizumab for asthma and allergic bronchopulmonary aspergillosis in adults with cystic fibrosis.

Background: In cystic fibrosis (CF), omalizumab has been used for difficult-to-treat asthma and allergic bronchopulmonary aspergillosis (ABPA) but safety and efficacy data are limited for this population.

Methods: We assessed patients receiving omalizumab for asthma or ABPA in the Toronto adult CF center between 2005 and 2017. We evaluated treatment safety and efficacy by analyzing changes in FEV% predicted (FEVpp) max value, slope and variability captured by the area under the curve (AUC), the cumulative dose of systemic corticosteroids (SCS), use of intravenous (IV) antibiotics and hospitalization days before omalizumab and up to 1 year after treatment initiation.

Hepatic enzyme ALT as a marker of glucose abnormality in men with cystic fibrosis.

Aim: Cystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). In non-CF patients, liver disease, specifically steatosis and non-alcoholic fatty liver disease (NAFLD), is strongly associated with type 2 diabetes. We compared glycemic status and metabolic profiles in CF patients according to a biomarker of hepatic injury, alanine aminotransferase (ALT).

The main mechanism associated with progression of glucose intolerance in older patients with cystic fibrosis is insulin resistance and not reduced insulin secretion capacity.

Background: Aging cystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). Decrease in insulin secretion over time is the main hypothesis to explain this increasing prevalence but mechanisms are still not well elucidated. The objective is to assess evolution of glucose tolerance and insulin secretion/sensitivity in aging CF patients.

Validation of the French 3-year prognostic score using the Canadian Cystic Fibrosis registry.

Studies of large CF populations using registry data are important to identify people at high risk for death. Nkam et al. published a prognostic score developed on French CF registry data to predict death or lung transplantation (LT) over a 3-year period in the adult CF population.

Neutrophils as a Potential Source of Chitinase-3-like Protein 1 in Cystic Fibrosis.

The chitinase-3-like protein 1, also known as YKL-40, is an inflammatory marker increased in blood of patients with cystic fibrosis (CF). Systemic levels of YKL-40 are increased in dysglycemic patients with CF. Our objective is to determine if YKL-40 is expressed and released by CF neutrophils.

Adrenal Insufficiency in Cystic Fibrosis: A Rare Phenomenon?

Background: The prevalence of adrenal insufficiency (AI) in cystic fibrosis (CF) is unknown. The frequent use of glucocorticoids (inhaled or systemic) may induce the long-term suppression of the hypothalamic-pituitary-adrenal axis.

Methods: We reviewed the results of adrenocorticotropic hormone (ACTH) stimulation tests done over a 10-year period to evaluate adrenal function in 69 CF patients of the CHUM CF clinic.

Stability of Commercially Available Glucagon Formulation for Dual-Hormone Artificial Pancreas Clinical Use.

Background: Available glucagon formulations are approved for immediate use after reconstitution for severe hypoglycemia emergency treatment. However, they are used in dual-hormone artificial pancreas (insulin and glucagon) studies through subcutaneous infusion pumps over 24 h. Chemical and physical stability of such glucagon use have not been reported in a comprehensive manner.

Proprotein Convertase Subtilisin/Kexin type 9 affects insulin but not lipid metabolism in cystic fibrosis.

Purpose: Cystic Fibrosis (CF) is the most common genetic disorder and, with improved survival, glucose abnormalities have emerged as a major comorbidity. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of plasma LDL-cholesterol homeostasis, is associated with lipid and glucose metabolism in healthy individuals. Here we report on the link between PCSK9 and markers of metabolism in CF.

Vitamin D 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 D 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.

Screening for Cystic Fibrosis-Related Diabetes: Matching Pathophysiology and Addressing Current Challenges.

Nearly 50% of adult patients with cystic fibrosis (CF) have diabetes. The occurrence of CF-related diabetes (CFRD) is preceded and is associated with deterioration of lung function and nutritional status. Microvascular complications can occur, but the main cause of death is respiratory failure rather than cardiovascular causes as in type 1 or type 2 diabetes.