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

Potter, Kathryn; Boudreau, Valérie; Shohoudi, Azadeh; Mailhot, M.; Tremblay, François; Lavoie, Annick; Carricart, Maite; Senior, Peter; Rabasa‐Lhoret, Rémi

doi:10.1016/j.jcf.2020.11.022

Cited by 19 publications

(15 citation statements)

References 25 publications

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“…Pancreatic insufficiency closely correlates with specific CFTR gene mutations [14]. Generally, patients with pancreatic exocrine sufficiency (CF-PS) display milder pulmonary disease and live longer than those with PI (CF-PI) [10,15]. Moreover, pancreatic exocrine insufficiency has been associated with an increase of 1-hour OGTT glucose, which was correlated with impaired beta-cell function, secretory capacity and worse clinical outcomes in pwCF displaying normal 2-hour standard OGTT glucose [16][17][18].…”

Section: Comparison Of Continuous Glucose Monitoring In Cystic Fibrosismentioning

confidence: 99%

Comparison of Continuous Glucose Monitoring in Cystic Fibrosis Patients With or Without Pancreatic Exocrine Insufficiency

et al. 2022

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Objective: This study aimed to compare continuous glucose monitoring (CGM) in cystic fibrosis (CF) according to pancreatic exocrine status. Methods: CGM and oral glucose tolerance testing (OGTT) were realized annually over five years in patients with CF (pwCF) aged ≥10 years without cystic fibrosis-related diabetes (CFRD). CGM parameters in patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and newly diagnosed CFRD were compared according to presence of pancreatic sufficiency (PS) or insufficiency (PI). Results: Overall, 547 OGTTs and 501 CGMs were performed in 147 CF patients, comprising 122 PI and 25 PS. In PS patients, 84% displayed NGT, 12% IGT, and 4% CFRD vs. 58%, 32%, and 10% (p=0.05) in PI. Among participants displaying normal OGTT, time in glucose range (70-140mg/dl) was significantly increased, 97% (93, 99) vs. 92% (85, 96), p<0.001, and time above glucose range significantly decreased, 1% (0, 2) % vs. 6% (2, 13), in patients with PS compared to those with PI. No significant differences were highlighted in patients with IGT. Conclusion: CGM revealed significant different glucose tolerance abnormalities in PI versus PS, which were undetected by standard 2-hour OGTT glucose.

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Section: Comparison Of Continuous Glucose Monitoring In Cystic Fibrosismentioning

confidence: 99%

Comparison of Continuous Glucose Monitoring in Cystic Fibrosis Patients With or Without Pancreatic Exocrine Insufficiency

et al. 2022

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“…A key specific point of abnormal glucose homeostasis in patients living with CF is an association with an increased risk of accelerated weight loss, lung function reduction, and accordingly, a marked increased risk of early death (51,52). Historically, it was reported that such risks start in the pre-diabetic glucose intolerance phase (53). Recently published data, however, indicate that improvement of overall CF management could modify some of the previously reported associations.…”

Section: Comparison Of Cfrd To Other Forms Of Diabetesmentioning

confidence: 99%

“…Recently published data, however, indicate that improvement of overall CF management could modify some of the previously reported associations. For example, CFRD onset is no longer preceded by a reduction in lung function and/or accelerated weight loss in the majority of patients (53).…”

Section: Comparison Of Cfrd To Other Forms Of Diabetesmentioning

confidence: 99%

“…Age, genotype and the presence of exocrine pancreatic deficiency are defined risk factors for CFRD. Notably, similar to insulin resistance (7,37,53,54), the prevalence of CFRD increases with age; around 2% of children, 19% of adolescents, and up to 50% of adult CF patients are diabetic (7). In addition, patients carrying severe mutations such as class I and II mutations have a higher risk of diabetes and pancreatic insufficiency compared to those with milder CFTR mutations (54).…”

Section: Risk Factors Associated With the Development Of Cfrdmentioning

confidence: 99%

“…In addition, patients carrying severe mutations such as class I and II mutations have a higher risk of diabetes and pancreatic insufficiency compared to those with milder CFTR mutations (54). Pancreatic insufficiency is closely associated with dysglycemia as well as low body mass index (BMI) and FEV1 (53). However, not all patients bearing identical CFTR mutations will develop CFRD and variation in diabetes onset as well as disease severity among CF patients with the same mutation suggest that additional factors contribute to CFRD.…”

Section: Risk Factors Associated With the Development Of Cfrdmentioning

confidence: 99%

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The Potential Causes of Cystic Fibrosis-Related Diabetes

et al. 2021

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Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity, affecting more than 50% of adult CF patients. Despite this high prevalence, the etiology of CFRD remains incompletely understood. Studies in young CF children show pancreatic islet disorganization, abnormal glucose tolerance, and delayed first-phase insulin secretion suggesting that islet dysfunction is an early feature of CF. Since insulin-producing pancreatic β-cells express very low levels of CFTR, CFRD likely results from β-cell extrinsic factors. In the vicinity of β-cells, CFTR is expressed in both the exocrine pancreas and the immune system. In the exocrine pancreas, CFTR mutations lead to the obstruction of the pancreatic ductal canal, inflammation, and immune cell infiltration, ultimately causing the destruction of the exocrine pancreas and remodeling of islets. Both inflammation and ductal cells have a direct effect on insulin secretion and could participate in CFRD development. CFTR mutations are also associated with inflammatory responses and excessive cytokine production by various immune cells, which infiltrate the pancreas and exert a negative impact on insulin secretion, causing dysregulation of glucose homeostasis in CF adults. In addition, the function of macrophages in shaping pancreatic islet development may be impaired by CFTR mutations, further contributing to the pancreatic islet structural defects as well as impaired first-phase insulin secretion observed in very young children. This review discusses the different factors that may contribute to CFRD.

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

Bonhoure,

Colomba,

Boudreau

et al. 2024

Clinical Nutrition ESPEN

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

Cited by 19 publications

References 25 publications

Comparison of Continuous Glucose Monitoring in Cystic Fibrosis Patients With or Without Pancreatic Exocrine Insufficiency

Comparison of Continuous Glucose Monitoring in Cystic Fibrosis Patients With or Without Pancreatic Exocrine Insufficiency

The Potential Causes of 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

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