Preservation of β-cell Function in Pancreatic Insufficient Cystic Fibrosis With Highly Effective CFTR Modulator Therapy

被引:0
|
作者
Flatt, Anneliese J. [1 ,2 ]
Sheikh, Saba [3 ,4 ]
Peleckis, Amy J. [1 ,2 ]
Alvarado, Paola [1 ,2 ]
Hadjiliadis, Denis [5 ]
Stefanovski, Darko [6 ]
Gallop, Robert J. [7 ]
Rubenstein, Ronald C. [8 ]
Kelly, Andrea [9 ,10 ]
Rickels, Michael R. [1 ,2 ]
机构
[1] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Dept Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA
[3] Univ Penn, Perelman Sch Med, Div Pulm & Sleep Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
[4] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA
[5] Univ Penn, Div Pulm & Crit Care Med, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA
[6] Univ Penn, New Bolton Ctr, Sch Vet Med, Kennett Sq, PA 19348 USA
[7] Univ Penn, Dept Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA
[8] Washington Univ, Div Allergy & Pulm Med, Dept Pediat, Sch Med, St Louis, MO 63110 USA
[9] Univ Penn, Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Perelman Sch Med, Philadelphia, PA 19104 USA
[10] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA
来源
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2024年 / 109卷 / 01期
基金
美国国家卫生研究院;
关键词
cystic fibrosis-related diabetes; cystic fibrosis transmembrane conductance regulator; highly effective modulator therapy; beta-cell secretory capacity; insulin secretion; SECRETORY CAPACITY; CLINICAL EFFECTIVENESS; INSULIN-SECRETION; B-CELL; ELEXACAFTOR/TEZACAFTOR/IVACAFTOR; EPIDEMIOLOGY; SITAGLIPTIN; IVACAFTOR; PEOPLE; ADULTS;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta) enhances aberrant cystic fibrosis transmembrane conductance regulator function and may improve the insulin secretory defects associated with a deterioration in clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF). Objective: This longitudinal case-control study assessed changes in beta-cell function and secretory capacity measures over 2 visits in individuals with PI-CF who were initiated on ETI after the baseline visit (2012-2018) and (1) restudied between 2019 and 2021 (ETI group) vs (2) those restudied between 2015 and 2018 and not yet treated with cystic fibrosis transmembrane conductance regulator modulator therapy (controls). Methods: Nine ETI participants (mean +/- SD age, 25 +/- 5 years) and 8 matched controls were followed up after a median (interquartile range) 5 (4-7) and 3 (2-3) years, respectively (P < .01), with ETI initiation a median of 1 year before follow-up. Clinical outcomes, glucose-potentiated arginine, and mixed-meal tolerance test measures were assessed with comparisons of within- and between-group change by nonparametric testing. Results: Glucose-potentiated insulin and C-peptide responses to glucose-potentiated arginine deteriorated in controls but not in the ETI group, with C-peptide changes different between groups (P < .05). Deterioration in basal proinsulin secretory ratio was observed in controls but improved, as did the maximal arginine-induced proinsulin secretory ratio, in the ETI group (P < .05 for all comparisons). During mixed-meal tolerance testing, early insulin secretion improved as evidenced by more rapid insulin secretory rate kinetics. Conclusion: ETI preserves beta-cell function in CF through effects on glucose-dependent insulin secretion, proinsulin processing, and meal-related insulin secretion. Further work should determine whether early intervention with ETI can prevent deterioration of glucose tolerance in PI-CF.
引用
收藏
页码:151 / 160
页数:10
相关论文
共 50 条
  • [21] Combination CFTR modulator therapy in children and adults with cystic fibrosis
    Guimbellot, Jennifer
    Taylor-Cousar, Jennifer
    LANCET RESPIRATORY MEDICINE, 2021, 9 (07): : 677 - 679
  • [22] EFFECT OF HIGHLY EFFECTIVE MODULATOR THERAPY ON QUALITY OF LIFE IN ADULTS WITH CYSTIC FIBROSIS
    Simpson, K. R.
    Keating, C.
    Overdevest, J.
    Gudis, D.
    DiMango, E.
    PEDIATRIC PULMONOLOGY, 2020, 55 : S273 - S273
  • [23] Obstructive sleep apnea in children with cystic fibrosis on highly effective modulator therapy
    Shakkottai, Aarti
    Kim, Stephany
    Mitchell, Ron B.
    PEDIATRIC PULMONOLOGY, 2024, 59 (10) : 2535 - 2542
  • [24] Effect of highly effective modulator therapy on quality of life in adults with cystic fibrosis
    DiMango, Emily
    Spielman, Daniel B.
    Overdevest, Jonathan
    Keating, Claire
    Francis, Sarah Fracasso
    Dansky, David
    Gudis, David A.
    INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY, 2021, 11 (01) : 75 - 78
  • [25] CFTR Modulator Therapies for Cystic Fibrosis
    Trimble, Aaron T.
    Donaldson, Scott H.
    PEDIATRIC ALLERGY IMMUNOLOGY AND PULMONOLOGY, 2015, 28 (04) : 230 - 236
  • [26] The role of CFTR in the eye, and the effect of early highly effective modulator treatment for cystic fibrosis on eye health
    Schneider-Futschik, Elena K.
    Zhu, Yimin
    Li, Danni
    Habgood, Mark D.
    Nguyen, Bao N.
    Pankonien, Ines
    Amaral, Margarida D.
    Downie, Laura E.
    Chinnery, Holly R.
    PROGRESS IN RETINAL AND EYE RESEARCH, 2024, 103
  • [27] Entering the era of highly effective CFTR modulator therapy
    Zemanick, Edith T.
    Accurso, Frank J.
    LANCET, 2019, 394 (10212): : 1886 - 1888
  • [28] EFFECTS OF CFTR MODULATOR THERAPY ON PANCREATIC EXOCRINE AND ENDOCRINE FUNCTION IN PEDIATRIC CYSTIC FIBROSIS PATIENTS: A PROPENSITY SCORE MATCHING STUDY
    Brenner, Todd A.
    Challa, Suryanarayana Reddy
    Singh, Anmol
    Gurakar, Merve
    Szvarca, Daniel
    Bhullar, Furqan A.
    Mckee, Katherine
    Vanscoy, Lori L.
    Cutting, Garry
    Mogayzel, Peter
    Singh, Vikesh
    Akshintala, Venkata S.
    GASTROENTEROLOGY, 2022, 162 (07) : S377 - S377
  • [29] Innate Immunity in Cystic Fibrosis: Varied Effects of CFTR Modulator Therapy on Cell-to-Cell Communication
    Hynes, Jennifer
    Taggart, Clifford C.
    Tirouvanziam, Rabindra
    Coppinger, Judith A.
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2025, 26 (06)
  • [30] CFTR Modulator Therapy and Its Impact on Lung Transplantation in Cystic Fibrosis
    Benden, Christian
    Schwarz, Carsten
    PULMONARY THERAPY, 2021, 7 (02) : 377 - 393