4.4 Review

Cystic fibrosis related diabetes (CFRD) in the era of modulators: A scoping review

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Effect of elexacaftor-tezacaftor-ivacaftor on body weight and metabolic parameters in adults with cystic fibrosis

Max C. Petersen et al.

Summary: This retrospective observational study examined the effects of elexacaftor-tezacaftor-ivacaftor on body weight and cardiometabolic parameters in 134 adult CF patients. The results showed an increase in BMI and changes in other cardiovascular risk factors after the initiation of elexacaftor-tezacaftor-ivacaftor. These findings suggest that widespread use of this medication may lead to overnutrition in the CF population.

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Gregory S. Sawicki et al.

Summary: This study assessed the long-term safety and efficacy of tezacaftor/ivacaftor in children with cystic fibrosis. The results showed that the treatment effects of tezacaftor/ivacaftor were maintained for up to 120 weeks, and it was generally safe and well tolerated.

JOURNAL OF CYSTIC FIBROSIS (2022)

Article Respiratory System

The effect of elexacaftor/tezacaftor/ivacaftor (ETI) on glycemia in adults with cystic fibrosis

Kevin J. Scully et al.

Summary: This study investigates the effect of elexacaftor-tezacaftor-ivacaftor (ETI) initiation on glycemia in adults with cystic fibrosis (CF). The results show that ETI treatment is associated with improvements in hyperglycemia and glycemic variability, but has no effect on hypoglycemia. The improvements are most notable in individuals with cystic fibrosis related diabetes (CFRD).

JOURNAL OF CYSTIC FIBROSIS (2022)

Article Respiratory System

A case report of CFTR modulator administration via carrier mother to treat meconium ileus in a F508del homozygous fetus

Sylvia Szentpetery et al.

Summary: This case report describes the treatment of a pregnant woman with F508del homozygous fetus using elexacaftor-tezacaftor-ivacaftor (ETI). The treatment resulted in resolution of meconium ileus (MI) and the delivery of a healthy baby. The mother continued ETI treatment while breastfeeding.

JOURNAL OF CYSTIC FIBROSIS (2022)

Article Pediatrics

Short-Term Effects of Elexacaftor/Tezacaftor/Ivacaftor Combination on Glucose Tolerance in Young People With Cystic Fibrosis-An Observational Pilot Study

Insa Korten et al.

Summary: ELX/TEZ/IVA therapy improves glucose tolerance in individuals with CF, suggesting potential benefits in preventing or delaying CFRD.

FRONTIERS IN PEDIATRICS (2022)

Article Critical Care Medicine

Ivacaftor in Infants Aged 4 to <12 Months with Cystic Fibrosis and a Gating Mutation Results of a Two-Part Phase 3 Clinical Trial

Jane C. Davies et al.

Summary: The study demonstrates that ivacaftor is safe and effective in infants aged 4 to 12 months with cystic fibrosis and gating mutations, showing good results in terms of pharmacokinetics and safety in this age group.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2021)

Article Respiratory System

Lumacaf tor/ivacaf tor therapy fails to increase insulin secretion in F508del/F508del CF patients

Amir Moheet et al.

Summary: In this study, lumacaftor/ivacaftor therapy did not improve insulin secretion or glucose tolerance in CF patients homozygous for the F508del mutation, as compared to baseline measurements.

JOURNAL OF CYSTIC FIBROSIS (2021)

Article Respiratory System

A phase 3, double-blind, parallel-group study to evaluate the efficacy and safety of tezacaftor in combination with ivacaftor in participants 6 through 11 years of age with cystic fibrosis homozygous for F508del or heterozygous for the F508del-CFTR mutation and a residual function mutation

Jane C. Davies et al.

Summary: Tezacaftor/ivacaftor demonstrated efficacy in improving lung function and CFTR function in patients aged 6 to 11 with F/F or F/RF genotypes, while also being safe and well tolerated with no new safety concerns identified.

JOURNAL OF CYSTIC FIBROSIS (2021)

Article Endocrinology & Metabolism

Effect of CFTR modulator therapy on cystic fibrosis-related diabetes

Holly Gaines et al.

Summary: The study found that about one-third of CF patients receiving CFTR modulator therapy had resolution or near resolution of CFRD, demonstrating the effectiveness of this treatment.

JOURNAL OF DIABETES AND ITS COMPLICATIONS (2021)

Article Cell Biology

Expression of miRNA-29 in Pancreatic β Cells Promotes Inflammation and Diabetes via TRAF3

Yi Sun et al.

Summary: Type 2 diabetes mellitus is a chronic, low-grade inflammatory disease characterized by insulin resistance and pancreatic beta cell dysfunction. Research has shown that miR-29 can modulate glucose metabolism and insulin sensitivity by regulating the beta cell-macrophage crosstalk pathway.

CELL REPORTS (2021)

Article Endocrinology & Metabolism

Lumacaftor/ivacaftor in cystic fibrosis: effects on glucose metabolism and insulin secretion

C. Colombo et al.

Summary: The study evaluated the variation in glucose metabolism and insulin secretion in CF patients homozygous for Phe508del CFTR mutation after one-year treatment with LUMA/IVA compared to patients with the same genotype who did not receive such treatment, finding no evidence of improvements in glucose tolerance mechanisms.

JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION (2021)

Review Respiratory System

Cystic fibrosis-related diabetes and lung disease: an update

Bernadette J. Prentice et al.

Summary: The development of cystic fibrosis-related diabetes (CFRD) often leads to poorer outcomes in patients with cystic fibrosis, including increases in pulmonary exacerbations, poorer lung function, and early mortality. Nutritional factors, the direct effect of hyperglycemia on the lungs, the immunomodulatory effects of high glucose levels, and the potential role of genetic modifiers are highlighted as contributing factors to the clinical decline seen in patients diagnosed with CFRD.

EUROPEAN RESPIRATORY REVIEW (2021)

Article Critical Care Medicine

Long-term safety of lumacaftor-ivacaftor in children aged 2-5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study

Jordana E. Hoppe et al.

Summary: The study demonstrated that lumacaftor-ivacaftor is generally safe and well tolerated for long-term use in children with cystic fibrosis aged 2-5 years, and treatment effects are maintained over time.

LANCET RESPIRATORY MEDICINE (2021)

Article Endocrinology & Metabolism

Impaired glucose tolerance and indeterminate glycemia in cystic fibrosis

Nader Kasim et al.

Summary: Oral glucose tolerance testing is the primary method to screen for and diagnose cystic fibrosis-related diabetes, abnormal glucose tolerance is associated with CF outcomes, further studies are needed to understand the implications of IGT and INDET.

JOURNAL OF CLINICAL AND TRANSLATIONAL ENDOCRINOLOGY (2021)

Article Critical Care Medicine

Long-term safety and efficacy of lumacaftor-ivacaftor therapy in children aged 6-11 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a phase 3, open-label, extension study

Mark Chilvers et al.

Summary: This study demonstrates the long-term safety and efficacy of lumacaftor-ivacaftor combination therapy in children with cystic fibrosis homozygous for the F508del-CFTR mutation aged 6-11 years, with sustained efficacy for up to 120 weeks. The treatment was well tolerated with minimal adverse events.

LANCET RESPIRATORY MEDICINE (2021)

Article Endocrinology & Metabolism

In Situ Analysis Reveals That CFTR Is Expressed in Only a Small Minority of β-Cells in Normal Adult Human Pancreas

Michael G. White et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2020)

Article Respiratory System

Glucose abnormalities detected by continuous glucose monitoring are common in young children with Cystic Fibrosis

Bernadette J. Prentice et al.

JOURNAL OF CYSTIC FIBROSIS (2020)

Article Multidisciplinary Sciences

Heterogeneous expression of CFTR in insulin-secreting β-cells of the normal human islet

Mauricio Di Fulvio et al.

PLOS ONE (2020)

Review Respiratory System

The Extrapulmonary Effects of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis

Valentine Sergeev et al.

ANNALS OF THE AMERICAN THORACIC SOCIETY (2020)

Article Critical Care Medicine

Islet Hormone and Incretin Secretion in Cystic Fibrosis after Four Months of Ivacaftor Therapy

Andrea Kelly et al.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2019)

Article Respiratory System

Continuous glucose monitoring in youth with cystic fibrosis treated with lumacaftor-ivacaftor

Angel Li et al.

JOURNAL OF CYSTIC FIBROSIS (2019)

Article Respiratory System

Lumacaftor-rescued F508del-CFTR has a modified bicarbonate permeability

Loretta Ferrera et al.

JOURNAL OF CYSTIC FIBROSIS (2019)

Article Respiratory System

Early glucose abnormalities are associated with pulmonary inflammation in young children with cystic fibrosis

Bernadette J. Prentice et al.

JOURNAL OF CYSTIC FIBROSIS (2019)

Review Endocrinology & Metabolism

Survival in a bad neighborhood: pancreatic islets in cystic fibrosis

Andrew W. Norris et al.

JOURNAL OF ENDOCRINOLOGY (2019)

Article Medicine, General & Internal

Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele

P. G. Middleton et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Article Medicine, General & Internal

Sustained Glycemic Control With Ivacaftor in Cystic Fibrosis-Related Diabetes

Francis Christian et al.

JOURNAL OF INVESTIGATIVE MEDICINE HIGH IMPACT CASE REPORTS (2019)

Article Respiratory System

Continuous glucose monitoring abnormalities in cystic fibrosis youth correlate with pulmonary function decline

Christine L. Chan et al.

JOURNAL OF CYSTIC FIBROSIS (2018)

Article Medicine, General & Internal

VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles

Dominic Keating et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Article Medicine, Research & Experimental

Cystic fibrosis-related diabetes is caused by islet loss and inflammation

Nathaniel J. Hart et al.

JCI INSIGHT (2018)

Article Medicine, General & Internal

Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis

Steven M. Rowe et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Article Cardiac & Cardiovascular Systems

Ivacaftor for the p.Ser549Arg (S549R) gating mutation - The Israeli experience

Adi Dagan et al.

RESPIRATORY MEDICINE (2017)

Article Gastroenterology & Hepatology

Impact of CFTR Modulation on Intestinal pH, Motility, and Clinical Outcomes in Patients With Cystic Fibrosis and the G551D Mutation

Daniel Gelfond et al.

CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY (2017)

Article Critical Care Medicine

Abnormal Glucose Tolerance in Infants and Young Children with Cystic Fibrosis

Yaling Yi et al.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2016)

Article Medicine, General & Internal

Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR

C. E. Wainwright et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

Article Respiratory System

CFTR potentiator therapy ameliorates impaired insulin secretion in CF patients with a gating mutation

Reuven Tsabari et al.

Journal of Cystic Fibrosis (2015)

Letter Critical Care Medicine

Resolution of Cystic Fibrosis-related Diabetes with lvacaftor Therapy

Don Hayes et al.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2014)

Article Endocrinology & Metabolism

Genetic Modifiers of Cystic Fibrosis-Related Diabetes

Scott M. Blackman et al.

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Insulin secretion improves in cystic fibrosis following ivacaftor correction of CFTR: a small pilot study

Melena D. Bellin et al.

PEDIATRIC DIABETES (2013)

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A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation

Bonnie W. Ramsey et al.

NEW ENGLAND JOURNAL OF MEDICINE (2011)

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Impaired Fasting Glucose in Cystic Fibrosis

Brigitte I. Frohnert et al.

DIABETES CARE (2010)

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Katie Larson Ode et al.

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Cytokines in the Progression of Pancreatic beta-Cell Dysfunction

Chunjiong Wang et al.

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (2010)

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Cystic Fibrosis-Related Diabetes: Current Trends in Prevalence, Incidence, and Mortality

Antoinette Moran et al.

DIABETES CARE (2009)

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Carl de Luca et al.

FEBS LETTERS (2008)

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New criteria for impaired fasting glucose and screening for diabetes in cystic fibrosis

C Mueller-Brandes et al.

EUROPEAN RESPIRATORY JOURNAL (2005)

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Insulin-secretion abnormalities and clinical deterioration related to impaired glucose tolerance in cystic fibrosis

S Tofé et al.

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2005)